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Wang X, Zheng Z, Yu D, Qiu X, Yang T, Li R, Liu J, Wang X, Jin P, Sheng J, Qin N, Li N, Xu J. Colorectal cancer in Lynch syndrome families: consequences of gene germline mutations and the gut microbiota. Orphanet J Rare Dis 2025; 20:30. [PMID: 39827259 PMCID: PMC11742751 DOI: 10.1186/s13023-025-03543-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Accepted: 01/02/2025] [Indexed: 01/22/2025] Open
Abstract
BACKGROUND Lynch syndrome (LS)-associated colorectal cancer (CRC) always ascribes to pathogenic germline mutations in mismatch repair (MMR) genes. However, the penetrance of CRC varies among those with the same MMR gene mutation. Thus, we hypothesized that the gut microbiota is also involved in CRC development in LS families. METHODS This prospective, observational study was performed from December 2020 to March 2023. We enrolled 72 individuals from 9 LS families across six provinces in China and employed 16S rRNA gene amplicon sequencing to analyze the fecal microbiota components among LS-related CRC patients (AS group), their spouses (BS group), mutation carriers without CRC (CS group), and non-mutation carriers (DS group) using alpha and beta diversity indices. RESULTS There were no apparent differences in age or gender among the four groups. Alpha and beta diversity indices exhibited no significant differences between the AS and BS groups, verifying the role of germline mutations in the occurrence of CRC in LS families. Beta diversity analysis exhibited significant differences between the AS and CS groups, revealing the importance of the gut microbiota for the occurrence of CRC in LS families. A greater difference (both alpha and beta diversity indices) was shown between the AS and DS groups, demonstrating the combined impact of the gut microbiota and genetic germline mutations on the occurrence of CRC in LS families. Compared with those in the CS and DS groups, we identified ten microbial genera enriched in the AS group, and one genus (Bacteroides) decreased in the AS group. Among the elevated genera in the AS group, Agathobacter, Coprococcus and Prevotellaceae_NK3B31_group were butyrate-producing genera. CONCLUSION This study found the development of CRC in the LS families can be attributed to the combined effects of gene germline mutations as well as the gut microbiota and provided novel insights into the prevention and treatment of CRC in the LS families.
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Affiliation(s)
- Xuexin Wang
- Medical School of Chinese PLA, Beijing, 100853, China
- Senior Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China
| | - Zhijun Zheng
- Realbio Genomics Institute, Shanghai, 201114, China.
| | - Dongliang Yu
- Department of Gastroenterology, The Seventh Medical Center of Chinese PLA General Hospital, Beijing, 100700, China
| | - Xiaojue Qiu
- Senior Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China
| | - Ting Yang
- Senior Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China
| | - Ruoran Li
- Medical School of Chinese PLA, Beijing, 100853, China
| | - Jing Liu
- Realbio Genomics Institute, Shanghai, 201114, China
- Tenth People's Hospital of Tongji University, Shanghai, 200072, China
| | - Xin Wang
- Department of Gastroenterology, The Seventh Medical Center of Chinese PLA General Hospital, Beijing, 100700, China
| | - Peng Jin
- Department of Gastroenterology, The Seventh Medical Center of Chinese PLA General Hospital, Beijing, 100700, China
- Senior Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China
| | - Jianqiu Sheng
- Department of Gastroenterology, The Seventh Medical Center of Chinese PLA General Hospital, Beijing, 100700, China
| | - Nan Qin
- Tenth People's Hospital of Tongji University, Shanghai, 200072, China
- Qingdao Realbio Precision Medical Test Co. Ltd, Qingdao, 266071, China
| | - Na Li
- Medical School of Chinese PLA, Beijing, 100853, China.
- Senior Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China.
| | - Junfeng Xu
- Senior Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China.
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Ndou L, Chambuso R, Algar U, Boutall A, Goldberg P, Ramesar R. Genomic Medicine in the Developing World: Cancer Spectrum, Cumulative Risk and Survival Outcomes for Lynch Syndrome Variant Heterozygotes with Germline Pathogenic Variants in the MLH1 and MSH2 Genes. Biomedicines 2024; 12:2906. [PMID: 39767815 PMCID: PMC11672899 DOI: 10.3390/biomedicines12122906] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Revised: 12/17/2024] [Accepted: 12/18/2024] [Indexed: 01/11/2025] Open
Abstract
Background: Although genetic testing has improved our ability to diagnose Lynch syndrome (LS), there is still limited information on the extent of variations in the clinical and genetic landscape among LS variant heterozygotes (LSVH) in Africa. We sought to investigate the cancer spectrum, cumulative risk, and survival outcomes of LSVH with pathogenic/likely pathogenic variants (P/LPVs) in the MLH1 and MSH2 genes using a LS registry in South Africa over the last 30 years. Methods: A retrospective study was conducted to retrieve demographic, clinical, and genetic data of all LSVH with P/LPVs in the MLH1 and MSH2 genes from our LS registry. Genetic data were analyzed according to cancer spectrum, cumulative risk, and crude survival. We used the Chi-squared and t-test to assess differences between groups, and Kaplan-Meier survival analyses were used to analyze the cumulative risk and crude survival outcomes. A p-value < 0.05 at a 95% confidence interval was considered statistically significant. Results: We analyzed a total of 577 LSVH from 109 families. About 450 (78%) and 127 (22%) LSVH harbored a disease-causing mutation in MLH1 and MSH2, respectively. A South African founder PV (MLH1:c.1528C>T) accounted for 74% (n = 426) of all LSVH. CRC was the most common diagnosed cancer in both MLH1 and MSH2 LSVH. MLH1 LSVH had a younger age at cancer diagnosis than MSH2 LSVH (43 vs. 47 years, respectively, p = 0.015). Extracolonic cancers were predominantly higher in female LSVH (n = 33, 35%) than in male LSVH (n = 8, 7%) with the MLH1:c.1528C>T founder PV. The cumulative risk of any cancer and CRC at any age was higher in MLH1 LSVH than in MSH2 LSVH (p = 0.020 and p = 0.036, respectively). LSVH with the MLH1:c.1528C>T PV had a better 10-year overall survival after the first cancer diagnosis, particularly for CRC. Conclusions: LSVH with P/LPVs in the MLH1 and MSH2 genes exhibited significant gene- and sex-specific differences in cancer spectrum, cumulative risk and survival outcomes. Cancer risk and survival estimates described in this study can be used to guide surveillance and genetic counselling for LSVH in our population.
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Affiliation(s)
- Lutricia Ndou
- UCT/MRC Genomic and Precision Medicine Research Unit, Division of Human Genetics, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, and Affiliated Hospitals, Cape Town 7704, South Africa; (L.N.); (R.C.)
| | - Ramadhani Chambuso
- UCT/MRC Genomic and Precision Medicine Research Unit, Division of Human Genetics, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, and Affiliated Hospitals, Cape Town 7704, South Africa; (L.N.); (R.C.)
| | - Ursula Algar
- The Colorectal Unit, Department of Surgery, Groote Schuur Hospital, The University of Cape Town, Cape Town 7925, South Africa
| | - Adam Boutall
- The Colorectal Unit, Department of Surgery, Groote Schuur Hospital, The University of Cape Town, Cape Town 7925, South Africa
| | - Paul Goldberg
- The Colorectal Unit, Department of Surgery, Groote Schuur Hospital, The University of Cape Town, Cape Town 7925, South Africa
| | - Raj Ramesar
- UCT/MRC Genomic and Precision Medicine Research Unit, Division of Human Genetics, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, and Affiliated Hospitals, Cape Town 7704, South Africa; (L.N.); (R.C.)
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Liu L, Sun T, Liu H, Li J, Tian L. Carbohydrate quality vs quantity on cancer Risk: Perspective of microbiome mechanisms. J Funct Foods 2024; 118:106246. [DOI: 10.1016/j.jff.2024.106246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/15/2025] Open
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Rifkin SB, Sze MA, Tuck K, Koeppe E, Stoffel EM, Schloss PD. Gut Microbiome Composition in Lynch Syndrome With and Without History of Colorectal Neoplasia and Non-Lynch Controls. J Gastrointest Cancer 2024; 55:207-218. [PMID: 37310549 DOI: 10.1007/s12029-023-00925-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/24/2023] [Indexed: 06/14/2023]
Abstract
BACKGROUND While Lynch syndrome (LS) is a highly penetrant colorectal cancer (CRC) syndrome, there is considerable variation in penetrance; few studies have investigated the association between microbiome and CRC risk in LS. We analyzed the microbiome composition among individuals with LS with and without personal history of colorectal neoplasia (CRN) and non-LS controls. METHODS We sequenced the V4 region of the 16S rRNA gene from the stool of 46 individuals with LS and 53 individuals without LS. We characterized within community and in between community microbiome variation, compared taxon abundance, and built machine learning models to investigate the differences in microbiome. RESULTS There was no difference within or between community variations among LS groups, but there was a statistically significant difference in both within and between community variation comparing LS to non-LS. Streptococcus and Actinomyces were differentially enriched in LS-CRC compared to LS-without CRN. There were numerous differences in taxa abundance comparing LS to non-LS; notably, Veillonella was enriched and Faecalibacterium and Romboutsia were depleted in LS. Finally, machine learning models classifying LS from non-LS controls and LS-CRC from LS-without CRN performed moderately well. CONCLUSIONS Differences in microbiome composition between LS and non-LS may suggest a microbiome pattern unique to LS formed by underlying differences in epithelial biology and immunology. We found specific taxa differences among LS groups, which may be due to underlying anatomy. Larger prospective studies following for CRN diagnosis and microbiome composition changes are needed to determine if microbiome composition contributes to CRN development in patients with LS.
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Affiliation(s)
- S B Rifkin
- Department of Internal Medicine, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, 48109, USA.
- Division of Gastroenterology and Hepatology, University of Michigan School of Medicine, Ann Arbor, MI, 48109, USA.
| | - M A Sze
- Department of Immunology and Microbiology, University of Michigan, Ann Arbor, MI, 48109, USA
| | - K Tuck
- Department of Internal Medicine, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, 48109, USA
| | - E Koeppe
- Department of Internal Medicine, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, 48109, USA
- Division of Gastroenterology and Hepatology, University of Michigan School of Medicine, Ann Arbor, MI, 48109, USA
| | - E M Stoffel
- Department of Internal Medicine, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, 48109, USA
- Division of Gastroenterology and Hepatology, University of Michigan School of Medicine, Ann Arbor, MI, 48109, USA
| | - P D Schloss
- Department of Immunology and Microbiology, University of Michigan, Ann Arbor, MI, 48109, USA
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Chevalier E, Benamouzig R. Chemoprevention in hereditary digestive neoplasia: A comprehensive review. Therap Adv Gastroenterol 2023; 16:17562848231215585. [PMID: 38050626 PMCID: PMC10693784 DOI: 10.1177/17562848231215585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Accepted: 10/23/2023] [Indexed: 12/06/2023] Open
Abstract
Hereditary syndromes, such as familial adenomatous polyposis (FAP), MUTYH polyposis or Lynch syndrome, are particularly predisposing to the development of colorectal cancer. These situations have necessitated the development of adapted prevention strategies based largely on reinforced endoscopic surveillance and the search for complementary prevention strategies. This is the case for chemoprevention, which is the long-term administration of chemical agents limiting carcinogenesis, used as primary or secondary prophylaxis. The aim of this review is to present the available literature and the latest advances in chemoprevention in patients with FAP or MUTYH and other polyposis as well as in patients with Lynch syndrome. The main conclusions of the few available guidelines in these situations are also discussed.
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Affiliation(s)
- Eugénie Chevalier
- Department of Gastroenterology and Digestive Oncology, Avicenne Hospital, Bobigny, France
| | - Robert Benamouzig
- Department of Gastroenterology and Digestive Oncology, Avicenne Hospital, AP-HP, Paris Nord la Sorbonne University, 125 Rue de Stalingrad, Bobigny 93000, France
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Ascrizzi S, Arillotta GM, Grillone K, Caridà G, Signorelli S, Ali A, Romeo C, Tassone P, Tagliaferri P. Lynch Syndrome Biopathology and Treatment: The Potential Role of microRNAs in Clinical Practice. Cancers (Basel) 2023; 15:3930. [PMID: 37568746 PMCID: PMC10417124 DOI: 10.3390/cancers15153930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Revised: 07/27/2023] [Accepted: 07/31/2023] [Indexed: 08/13/2023] Open
Abstract
Lynch syndrome (LS), also known as Hereditary Non-Polyposis Colorectal Cancer (HNPCC), is an autosomal dominant cancer syndrome which causes about 2-3% of cases of colorectal carcinoma. The development of LS is due to the genetic and epigenetic inactivation of genes involved in the DNA mismatch repair (MMR) system, causing an epiphenomenon known as microsatellite instability (MSI). Despite the fact that the genetics of the vast majority of MSI-positive (MSI+) cancers can be explained, the etiology of this specific subset is still poorly understood. As a possible new mechanism, it has been recently demonstrated that the overexpression of certain microRNAs (miRNAs, miRs), such as miR-155, miR-21, miR-137, can induce MSI or modulate the expression of the genes involved in LS pathogenesis. MiRNAs are small RNA molecules that regulate gene expression at the post-transcriptional level by playing a critical role in the modulation of key oncogenic pathways. Increasing evidence of the link between MSI and miRNAs in LS prompted a deeper investigation into the miRNome involved in these diseases. In this regard, in this study, we discuss the emerging role of miRNAs as crucial players in the onset and progression of LS as well as their potential use as disease biomarkers and therapeutic targets in the current view of precision medicine.
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Affiliation(s)
- Serena Ascrizzi
- Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy; (S.A.); (G.M.A.); (K.G.); (G.C.); (S.S.); (A.A.); (C.R.); (P.T.)
| | - Grazia Maria Arillotta
- Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy; (S.A.); (G.M.A.); (K.G.); (G.C.); (S.S.); (A.A.); (C.R.); (P.T.)
| | - Katia Grillone
- Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy; (S.A.); (G.M.A.); (K.G.); (G.C.); (S.S.); (A.A.); (C.R.); (P.T.)
| | - Giulio Caridà
- Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy; (S.A.); (G.M.A.); (K.G.); (G.C.); (S.S.); (A.A.); (C.R.); (P.T.)
| | - Stefania Signorelli
- Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy; (S.A.); (G.M.A.); (K.G.); (G.C.); (S.S.); (A.A.); (C.R.); (P.T.)
| | - Asad Ali
- Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy; (S.A.); (G.M.A.); (K.G.); (G.C.); (S.S.); (A.A.); (C.R.); (P.T.)
| | - Caterina Romeo
- Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy; (S.A.); (G.M.A.); (K.G.); (G.C.); (S.S.); (A.A.); (C.R.); (P.T.)
| | - Pierfrancesco Tassone
- Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy; (S.A.); (G.M.A.); (K.G.); (G.C.); (S.S.); (A.A.); (C.R.); (P.T.)
- Medical Oncology and Translational Medical Oncology Units, University Hospital Renato Dulbecco, 88100 Catanzaro, Italy
| | - Pierosandro Tagliaferri
- Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy; (S.A.); (G.M.A.); (K.G.); (G.C.); (S.S.); (A.A.); (C.R.); (P.T.)
- Medical Oncology and Translational Medical Oncology Units, University Hospital Renato Dulbecco, 88100 Catanzaro, Italy
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Abstract
The present paper reviews progress in research on dietary fibre and human health over the past five decades. There is now convincing evidence from prospective cohort studies that diets low in dietary fibre are associated with increased risk of common non-communicable diseases including CVD, type 2 diabetes and colorectal cancer. These findings provide strong support for hypotheses proposed by Denis Burkitt 50 years ago, based on very limited evidence but with considerable imagination and insight. For the first two to three decades of this period, research on dietary fibre was hampered by the lack of consensus about the definition, and measurement, of this complex and diverse dietary component and by the lack of appropriate tools for investigating the gut microbiome that is central to understanding mechanisms of action. Recent technical and scientific advances in microbiome research (based on fast, low-cost, DNA sequencing) are facilitating investigation of the associations between dietary fibre, the gut microbiome and human health. Current challenges include the need for agreement about the characteristics of a healthy gut microbiome. Although the health benefits attributed to higher dietary fibre intake are likely to be shared with most types of dietary fibre, one should anticipate that different sources of dietary fibre and the other components (resistant starch and non-digestible oligosaccharides) that make up dietary fibre will have characteristically different effects on human physiology and disease risk. In conclusion, population-level intakes of dietary fibre are low and there is a public health priority to develop and implement more effective interventions to increase intake.
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Affiliation(s)
- John C Mathers
- Human Nutrition & Exercise Research Centre, Centre for Healthier Lives, Population Health Sciences Institute, William Leech Building, Newcastle University, Newcastle on Tyne NE2 4HH, UK
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Andini KD, Nielsen M, Suerink M, Helderman NC, Koornstra JJ, Ahadova A, Kloor M, Mourits MJ, Kok K, Sijmons RH, Bajwa–ten Broeke SW. PMS2-associated Lynch syndrome: Past, present and future. Front Oncol 2023; 13:1127329. [PMID: 36895471 PMCID: PMC9989154 DOI: 10.3389/fonc.2023.1127329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Accepted: 02/01/2023] [Indexed: 02/25/2023] Open
Abstract
Carriers of any pathogenic variant in one of the MMR genes (path_MMR carriers) were traditionally thought to be at comparable risk of developing a range of different malignancies, foremost colorectal cancer (CRC) and endometrial cancer. However, it is now widely accepted that their cancer risk and cancer spectrum range notably depending on which MMR gene is affected. Moreover, there is increasing evidence that the MMR gene affected also influences the molecular pathogenesis of Lynch syndrome CRC. Although substantial progress has been made over the past decade in understanding these differences, many questions remain unanswered, especially pertaining to path_PMS2 carriers. Recent findings show that, while the cancer risk is relatively low, PMS2-deficient CRCs tend to show more aggressive behaviour and have a worse prognosis than other MMR-deficient CRCs. This, together with lower intratumoral immune infiltration, suggests that PMS2-deficient CRCs might have more in common biologically with sporadic MMR-proficient CRCs than with other MMR-deficient CRCs. These findings could have important consequences for surveillance, chemoprevention and therapeutic strategies (e.g. vaccines). In this review we discuss the current knowledge, current (clinical) challenges and knowledge gaps that should be targeted by future studies.
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Affiliation(s)
- Katarina D. Andini
- Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Maartje Nielsen
- Department of Clinical Genetics, Leiden University Medical Center, Leiden, Netherlands
| | - Manon Suerink
- Department of Clinical Genetics, Leiden University Medical Center, Leiden, Netherlands
| | - Noah C. Helderman
- Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Jan Jacob Koornstra
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Aysel Ahadova
- Department of Applied Tumour Biology, Institute of Pathology, Heidelberg University Hospital, and Clinical Cooperation Unit Applied Tumor Biology, German Cancer Research Center, Heidelberg, Germany
| | - Matthias Kloor
- Department of Applied Tumour Biology, Institute of Pathology, Heidelberg University Hospital, and Clinical Cooperation Unit Applied Tumor Biology, German Cancer Research Center, Heidelberg, Germany
| | - Marian J.E. Mourits
- Department of Gynaecology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Klaas Kok
- Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Rolf H. Sijmons
- Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Sanne W. Bajwa–ten Broeke
- Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
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Wan J, Li X, Gu M, Li Q, Wang C, Yuan R, Li L, Li X, Ye S, Chen J. The association of dietary resistance starch intake with all-cause and cause-specific mortality. Front Nutr 2022; 9:1004667. [PMID: 36570138 PMCID: PMC9773073 DOI: 10.3389/fnut.2022.1004667] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Accepted: 11/14/2022] [Indexed: 12/14/2022] Open
Abstract
Background Several studies have estimated daily intake of resistant starch (RS), but no studies have investigated the relationship of RS intake with mortality. Objective We aimed to examine associations between RS intake and all-cause and cause-specific mortality. Methods Data from US National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018 with 24-h dietary recall data was used in current study. The main exposure in this study was RS intake, and the main outcome was the mortality status of participants until December 31, 2019. The multivariable Cox proportional hazards regression models were developed to evaluate the hazard ratios (HRs) and 95% confidence interval (95% CI) of cardiovascular disease (CVD), cancer, and all-cause mortality associated with RS intake. Results A total of 42,586 US adults [mean (SD) age, 46.91 (16.88) years; 22,328 (52.43%) female] were included in the present analysis. During the 454,252 person-years of follow-up, 7,043 all-cause deaths occurred, including 1,809 deaths from CVD and 1,574 deaths from cancer. The multivariable-adjusted HRs for CVD, cancer, and all-cause mortality per quintile increase in RS intake were 1 (95%CI, 0.97-1.04), 0.96 (95%CI, 0.93-1), and 0.96 (95%CI, 0.95-0.98), respectively. The associations remained similar in the subgroup and sensitivity analyses. Conclusion Higher RS intake is significantly associated with lower cancer and all-cause mortality, but not significantly with CVD mortality. Future studies focusing on other populations with different food sources of RS and RS subtypes are needed to access the dose-response relationship and to improve global dietary recommendations.
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Affiliation(s)
- Jiang Wan
- Department of Epidemiology, Key Laboratory of Cardiovascular Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaocong Li
- Medical Research and Biometrics Center, National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Ming Gu
- Department of Cardiac Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qi Li
- Department of Nutrition, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Chuyun Wang
- Department of Nutrition, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Run Yuan
- Department of Nutrition, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lin Li
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiang Li
- Department of Nutrition, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China,Xiang Li
| | - Shaodong Ye
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China,Shaodong Ye
| | - Jichun Chen
- Department of Nutrition, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China,*Correspondence: Jichun Chen
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Mathers JC, Elliott F, Macrae F, Mecklin JP, Möslein G, McRonald FE, Bertario L, Evans DG, Gerdes AM, Ho JW, Lindblom A, Morrison PJ, Rashbass J, Ramesar RS, Seppälä TT, Thomas HJ, Sheth HJ, Pylvänäinen K, Reed L, Borthwick GM, Bishop DT, Burn J, on behalf of the CAPP2 Investigators. Cancer Prevention with Resistant Starch in Lynch Syndrome Patients in the CAPP2-Randomized Placebo Controlled Trial: Planned 10-Year Follow-up. Cancer Prev Res (Phila) 2022; 15:623-634. [PMID: 35878732 PMCID: PMC9433960 DOI: 10.1158/1940-6207.capr-22-0044] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 04/07/2022] [Accepted: 07/01/2022] [Indexed: 11/16/2022]
Abstract
ABSTRACT The CAPP2 trial investigated the long-term effects of aspirin and resistant starch on cancer incidence in patients with Lynch syndrome (LS). Participants with LS were randomized double-blind to 30 g resistant starch (RS) daily or placebo for up to 4 years. We present long-term cancer outcomes based on the planned 10-year follow-up from recruitment, supplemented by National Cancer Registry data to 20 years in England, Wales, and Finland. Overall, 463 participants received RS and 455 participants received placebo. After up to 20 years follow-up, there was no difference in colorectal cancer incidence (n = 52 diagnosed with colorectal cancer among those randomized to RS against n = 53 on placebo) but fewer participants had non-colorectal LS cancers in those randomized to RS (n = 27) compared with placebo (n = 48); intention-to-treat (ITT) analysis [HR, 0.54; 95% confidence interval (CI), 0.33-0.86; P = 0.010]. In ITT analysis, allowing for multiple primary cancer diagnoses among participants by calculating incidence rate ratios (IRR) confirmed the protective effect of RS against non-colorectal cancer LS cancers (IRR, 0.52; 95% CI, 0.32-0.84; P = 0.0075). These effects are particularly pronounced for cancers of the upper GI tract; 5 diagnoses in those on RS versus 21 diagnoses on placebo. The reduction in non-colorectal cancer LS cancers was detectable in the first 10 years and continued in the next decade. For colorectal cancer, ITT analysis showed no effect of RS on colorectal cancer risk (HR, 0.92; 95% CI, 0.62-1.34; P = 0.63). There was no interaction between aspirin and RS treatments. In conclusion, 30 g daily RS appears to have a substantial protective effect against non-colorectal cancer cancers for patients with LS. PREVENTION RELEVANCE Regular bowel screening and aspirin reduce colorectal cancer among patients with LS but extracolonic cancers are difficult to detect and manage. This study suggests that RS reduces morbidity associated with extracolonic cancers. See related Spotlight, p. 557.
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Affiliation(s)
- John C. Mathers
- Human Nutrition Research Centre, Population Heath Sciences Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Faye Elliott
- Division of Haematology and Immunology, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, United Kingdom
| | - Finlay Macrae
- Division Colorectal Medicine and Genetics, Royal Melbourne Hospital, Melbourne, Australia
| | - Jukka-Pekka Mecklin
- Department of Education & Research, Jyväskylä Central Hospital, Jyväskylä, Finland
- Sport & Health Sciences, University of Jyväskylä, Jyväskylä, Finland
| | - Gabriela Möslein
- Center for Hereditary Tumors, Ev. BEHESDA Khs. zu Duisburg GmbH, Germany
| | - Fiona E. McRonald
- National Cancer Registration and Analysis Service, Public Health England
| | - Lucio Bertario
- Instituto Nazionale per lo Studio e, la Cura dei Tumori, Milan, Italy
| | - D. Gareth Evans
- Division of Evolution and Genomic Medicine, University of Manchester, St Mary's Hospital, Manchester Universities Foundation Trust, Manchester, United Kingdom
| | - Anne-Marie Gerdes
- Medical Genetics Clinic, ICMM; Clinical Genetics, Rigshospital, Copenhagen, Denmark
| | - Judy W.C. Ho
- Hereditary GI Cancer Registry, Department of Surgery, Queen Mary Hospital, Hong Kong, China
| | - Annika Lindblom
- Department of Molecular Medicine & Surgery, Karolinska Institutet, Stockholm, Sweden
| | - Patrick J. Morrison
- The Department of Medical Genetics, Queens University Belfast, Belfast City Hospital HSC Trust, Belfast, United Kingdom
| | - Jem Rashbass
- National Cancer Registration and Analysis Service, Public Health England
| | - Raj S. Ramesar
- MRC Genomic and Precision Medicine Research Unit, Division of Human Genetics, Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory, South Africa
| | - Toni T. Seppälä
- Department of Gastrointestinal Surgery, Helsinki University Hospital, Helsinki, Finland
| | - Huw J.W. Thomas
- St Mark's Hospital, London & Faculty of Medicine, Imperial College London, London, United Kingdom
| | - Harsh J. Sheth
- Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, United Kingdom
| | - Kirsi Pylvänäinen
- Department of Education & Research, Jyväskylä Central Hospital, Jyväskylä, Finland
| | - Lynn Reed
- Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, United Kingdom
| | - Gillian M. Borthwick
- Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, United Kingdom
| | - D. Timothy Bishop
- Division of Haematology and Immunology, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, United Kingdom
| | - John Burn
- Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, United Kingdom
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11
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Bansal A, Montgomery R, Vilar E. Can a Banana a Day Keep the Cancer Away in Patients with Lynch Syndrome? Cancer Prev Res (Phila) 2022; 15:557-559. [DOI: 10.1158/1940-6207.capr-22-0312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 06/30/2022] [Accepted: 07/11/2022] [Indexed: 11/16/2022]
Abstract
Abstract
The CAPP2 investigators report on the long-term effects of resistant starch (RS) on the incidence of colorectal cancer and other Lynch syndrome–related tumors in the trial population of the CAPP-2 study. RS has no effect on colorectal cancer incidence, but it reduced the numbers of other Lynch syndrome–related tumors, mainly driven by upper gastrointestinal cancers. Although the study has limitations related to secondary analysis, it fills an important void in the field of cancer interception of non–colorectal Lynch syndrome–related tumors and should form the basis for future trials of RS in Lynch syndrome.
See related article, p. 623
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Affiliation(s)
- Ajay Bansal
- 1Division of Gastroenterology and Hepatology, The University of Kansas Medical Center, Kansas City, Kansas
- 2The University of Kansas Cancer Center, Kansas City, Kansas
| | - Robert Montgomery
- 3Department of Biostatistics and Data Science, The University of Kansas Medical Center, Kansas City, Kansas
| | - Eduardo Vilar
- 4Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas
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12
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Kadyan S, Sharma A, Arjmandi BH, Singh P, Nagpal R. Prebiotic Potential of Dietary Beans and Pulses and Their Resistant Starch for Aging-Associated Gut and Metabolic Health. Nutrients 2022; 14:nu14091726. [PMID: 35565693 PMCID: PMC9100130 DOI: 10.3390/nu14091726] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 04/18/2022] [Accepted: 04/19/2022] [Indexed: 01/27/2023] Open
Abstract
Dietary pulses, including dry beans, lentils, chickpeas, and dry peas, have the highest proportion of fiber among different legume cultivars and are inexpensive, easily accessible, and have a long shelf-life. The inclusion of pulses in regular dietary patterns is an easy and effective solution for achieving recommended fiber intake and maintaining a healthier gut and overall health. Dietary pulses-derived resistant starch (RS) is a relatively less explored prebiotic ingredient. Several in vitro and preclinical studies have elucidated the crucial role of RS in fostering and shaping the gut microbiota composition towards homeostasis thereby improving host metabolic health. However, in humans and aged animal models, the effect of only the cereals and tubers derived RS has been studied. In this context, this review collates literature pertaining to the beneficial effects of dietary pulses and their RS on gut microbiome-metabolome signatures in preclinical and clinical studies while contemplating their potential and prospects for better aging-associated gut health. In a nutshell, the incorporation of dietary pulses and their RS in diet fosters the growth of beneficial gut bacteria and significantly enhances the production of short-chain fatty acids in the colon.
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13
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Gheorghe AS, Negru ȘM, Preda M, Mihăilă RI, Komporaly IA, Dumitrescu EA, Lungulescu CV, Kajanto LA, Georgescu B, Radu EA, Stănculeanu DL. Biochemical and Metabolical Pathways Associated with Microbiota-Derived Butyrate in Colorectal Cancer and Omega-3 Fatty Acids Implications: A Narrative Review. Nutrients 2022; 14:nu14061152. [PMID: 35334808 PMCID: PMC8950877 DOI: 10.3390/nu14061152] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 03/02/2022] [Accepted: 03/07/2022] [Indexed: 02/01/2023] Open
Abstract
Knowledge regarding the influence of the microbial community in cancer promotion or protection has expanded even more through the study of bacterial metabolic products and how they can modulate cancer risk, which represents an extremely challenging approach for the relationship between intestinal microbiota and colorectal cancer (CRC). This review discusses research progress on the effect of bacterial dysbiosis from a metabolic point of view, particularly on the biochemical mechanisms of butyrate, one of the main short chain fatty acids (SCFAs) with anti-inflammatory and anti-tumor properties in CRC. Increased daily intake of omega-3 polyunsaturated fatty acids (PUFAs) significantly increases the density of bacteria that are known to produce butyrate. Omega-3 PUFAs have been proposed as a treatment to prevent gut microbiota dysregulation and lower the risk or progression of CRC.
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Affiliation(s)
- Adelina Silvana Gheorghe
- Department of Oncology, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (A.S.G.); (R.I.M.); (I.A.K.); (E.A.D.); (L.A.K.); (B.G.); (E.A.R.); (D.L.S.)
| | - Șerban Mircea Negru
- Department of Oncology, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timisoara, Romania
- Correspondence: (Ș.M.N.); (M.P.)
| | - Mădălina Preda
- Department of Microbiology, Parasitology and Virology, Faculty of Midwives and Nursing, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Correspondence: (Ș.M.N.); (M.P.)
| | - Raluca Ioana Mihăilă
- Department of Oncology, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (A.S.G.); (R.I.M.); (I.A.K.); (E.A.D.); (L.A.K.); (B.G.); (E.A.R.); (D.L.S.)
| | - Isabela Anda Komporaly
- Department of Oncology, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (A.S.G.); (R.I.M.); (I.A.K.); (E.A.D.); (L.A.K.); (B.G.); (E.A.R.); (D.L.S.)
| | - Elena Adriana Dumitrescu
- Department of Oncology, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (A.S.G.); (R.I.M.); (I.A.K.); (E.A.D.); (L.A.K.); (B.G.); (E.A.R.); (D.L.S.)
| | | | - Lidia Anca Kajanto
- Department of Oncology, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (A.S.G.); (R.I.M.); (I.A.K.); (E.A.D.); (L.A.K.); (B.G.); (E.A.R.); (D.L.S.)
| | - Bogdan Georgescu
- Department of Oncology, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (A.S.G.); (R.I.M.); (I.A.K.); (E.A.D.); (L.A.K.); (B.G.); (E.A.R.); (D.L.S.)
| | - Emanuel Alin Radu
- Department of Oncology, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (A.S.G.); (R.I.M.); (I.A.K.); (E.A.D.); (L.A.K.); (B.G.); (E.A.R.); (D.L.S.)
| | - Dana Lucia Stănculeanu
- Department of Oncology, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (A.S.G.); (R.I.M.); (I.A.K.); (E.A.D.); (L.A.K.); (B.G.); (E.A.R.); (D.L.S.)
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14
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Sobh M, Montroy J, Daham Z, Sibbald S, Lalu M, Stintzi A, Mack D, Fergusson DA. Tolerability and SCFA production after resistant starch supplementation in humans: a systematic review of randomized controlled studies. Am J Clin Nutr 2022; 115:608-618. [PMID: 34871343 DOI: 10.1093/ajcn/nqab402] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Revised: 11/06/2021] [Accepted: 11/29/2021] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Resistant starches (RSs) have been advocated as a dietary supplement to address microbiota dysbiosis. They are postulated to act through the production of SCFAs. Their clinical tolerability and effect on SCFA production has not been systematically evaluated. OBJECTIVES We conducted a systematic review of RS supplementation as an intervention in adults (healthy individuals and persons with medical conditions) participating in randomized controlled trials. The primary outcome was tolerability of RS supplementation, the secondary outcome was SCFA production. METHODS MEDLINE, Embase, and the Cochrane Central Register were searched. Articles were screened, and data extracted, independently and in duplicate. RESULTS A total of 39 trials met eligibility criteria, including a total of 2263 patients. Twenty-seven (69%) studies evaluated the impact of RS supplementation in healthy subjects whereas 12 (31%) studies included individuals with an underlying medical condition (e.g., obesity, prediabetes). Type 2 RS was most frequently investigated (29 studies). Of 12 studies performed in subjects with health conditions, 11 reported on tolerability. All studies showed that RS supplementation was tolerated; 9 of these studies used type 2 RS with doses of 20-40 g/d for >4 wk. Of 27 studies performed in healthy subjects, 20 reported on tolerability. In 14 studies, RS supplementation was tolerated, and the majority used type 2 RS with a dose between 20 and 40 g/d. Twenty-one (78%) studies reporting SCFAs used type 2 RS with a dose of 20-40 g/d for 1-4 wk. In 16 of 23 studies (70%), SCFA production was increased, in 7 studies there was no change in SCFA concentration before and after RS supplementation, and in 1 study SCFA concentration decreased. CONCLUSIONS Available evidence suggests that RS supplementation is tolerated in both healthy subjects and in those with an underlying medical condition. In addition, SCFA production was increased in most of the studies.
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Affiliation(s)
- Mohamad Sobh
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Joshua Montroy
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Zeinab Daham
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.,Departments of Medicine and Surgery, School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada
| | - Stephanie Sibbald
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Manoj Lalu
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.,Department of Anesthesiology and Pain Medicine, The Ottawa Hospital, Ottawa, Ontario, Canada.,Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Alain Stintzi
- Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada
| | - David Mack
- Inflammatory Bowel Disease Centre, Children's Hospital of Eastern Ontario, CHEO Research Institute, Ottawa, Ontario, Canada.,Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada
| | - Dean A Fergusson
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.,Departments of Medicine and Surgery, School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada
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15
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Macaron C, Mankaney GN, Haider M, Mouchli M, Hurley K, Burke CA. Chemoprevention Considerations in Patients with Hereditary Colorectal Cancer Syndromes. Gastrointest Endosc Clin N Am 2022; 32:131-146. [PMID: 34798982 DOI: 10.1016/j.giec.2021.08.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Secondary prevention of colorectal neoplasia with chemoprevention is long-studied area of research and clinical use in patients with the 2 most common hereditary colorectal cancer syndromes including Lynch syndrome and familial adenomatous polyposis. No medication is currently approved for use for the prevention of colorectal polyps or cancer in either the general population or individuals with the hereditary colorectal cancer syndromes. Emerging data in animal models and limited data in humans suggest vaccines may be the next breakthrough for neoplasia prevention in patients with hereditary colorectal cancer. Clinicians must acknowledge chemoprevention is an adjunct and does not supplant endoscopic surveillance.
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Affiliation(s)
- Carole Macaron
- Department of Gastroenterology, Hepatology and Nutrition, Desk A 30, 9500 Euclid Avenue, Cleveland, OH 44195, USA
| | - Gautam N Mankaney
- Department of Gastroenterology and Hepatology, Virginia Mason Franciscan Health, 1100 9th Avenue, Seattle, WA 98101, USA
| | - Mahnur Haider
- John W. Deming Department of Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, #8016, New Orleans, LA 70112, USA
| | - Mohamad Mouchli
- Department of Gastroenterology, Hepatology and Nutrition, Desk A 30, 9500 Euclid Avenue, Cleveland, OH 44195, USA; Department of Gastroenterology, Hepatology, and Nutrition, Digestive Disease and Surgical Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Karen Hurley
- Center for Behavioral Health, Desk P57, 9500 Euclid Avenue, Cleveland, OH 44195, USA
| | - Carol A Burke
- Department of Gastroenterology, Hepatology and Nutrition, Desk A 30, 9500 Euclid Avenue, Cleveland, OH 44195, USA; Department of Colorectal Surgery, Sanford R. Weiss MD Center for Hereditary Gastrointestinal Neoplasia, Digestive Disease and Surgical Institute, Cleveland Clinic, Cleveland, OH, USA.
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16
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Okada Y, Park SY, Wilkens LR, Maskarinec G, Shvetsov YB, Haiman C, Le Marchand L. White Rice Consumption and Risk for Colorectal Cancer among Japanese Americans: The Multiethnic Cohort Study. J Epidemiol 2021; 33:170-176. [PMID: 34380917 PMCID: PMC9939926 DOI: 10.2188/jea.je20200611] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND White rice is a staple food for Japanese, a population at high risk for colorectal cancer (CRC). We investigated the association between white rice intake and CRC among Japanese Americans in the Multiethnic Cohort (MEC) study. METHODS The Multiethnic Cohort Study is a prospective study established in Hawaii and California in 1993-1996. Usual dietary intake was assessed by a validated quantitative food frequency questionnaire at baseline. Cox proportional hazards models were used to compute hazard ratios (HR) and 95% confidence intervals (CI) for quartiles of intake and to perform trend tests across sex-specific quartiles with adjustment for relevant confounders. RESULTS We identified 1,553 invasive CRC cases among 49,136 Japanese Americans (23,595 men and 25,541 women) during a mean follow-up of 19 years. White rice consumption was not associated with overall CRC incidence in men (p-trend = 0.11) or women (p-trend = 0.56). After excluding participants with a history of diabetes, the inverse associations were significant for CRC (p-trend = 0.03, HR for quartile 4 (Q4) vs. 1 = 0.81; 95% CI: 0.64-1.03) and tumors of the distal colon (p-trend = 0.006, HR for Q4 vs. Q1: 0.66; 0.44-0.99) among men but not women. CONCLUSIONS White rice consumption was not associated with an increased risk of overall CRC among Japanese Americans. An inverse association was observed with risk of CRC and distal colon cancer in men without a history of diabetes.
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Affiliation(s)
- Yuito Okada
- Population Sciences in the Pacific Program, University of Hawaii Cancer Center.,Office of Public Health Studies, University of Hawaii
| | - Song-Yi Park
- Population Sciences in the Pacific Program, University of Hawaii Cancer Center
| | - Lynne R Wilkens
- Population Sciences in the Pacific Program, University of Hawaii Cancer Center
| | - Gertraud Maskarinec
- Population Sciences in the Pacific Program, University of Hawaii Cancer Center
| | - Yurii B Shvetsov
- Population Sciences in the Pacific Program, University of Hawaii Cancer Center
| | - Christopher Haiman
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California
| | - Loïc Le Marchand
- Population Sciences in the Pacific Program, University of Hawaii Cancer Center
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17
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The Function of the Histamine H4 Receptor in Inflammatory and Inflammation-Associated Diseases of the Gut. Int J Mol Sci 2021; 22:ijms22116116. [PMID: 34204101 PMCID: PMC8200986 DOI: 10.3390/ijms22116116] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 05/31/2021] [Accepted: 06/03/2021] [Indexed: 02/07/2023] Open
Abstract
Histamine is a pleiotropic mediator involved in a broad spectrum of (patho)-physiological processes, one of which is the regulation of inflammation. Compounds acting on three out of the four known histamine receptors are approved for clinical use. These approved compounds comprise histamine H1-receptor (H1R) antagonists, which are used to control allergic inflammation, antagonists at H2R, which therapeutically decrease gastric acid release, and an antagonist at H3R, which is indicated to treat narcolepsy. Ligands at H4R are still being tested pre-clinically and in clinical trials of inflammatory diseases, including rheumatoid arthritis, asthma, dermatitis, and psoriasis. These trials, however, documented only moderate beneficial effects of H4R ligands so far. Nevertheless, pre-clinically, H4R still is subject of ongoing research, analyzing various inflammatory, allergic, and autoimmune diseases. During inflammatory reactions in gut tissues, histamine concentrations rise in affected areas, indicating its possible biological effect. Indeed, in histamine-deficient mice experimentally induced inflammation of the gut is reduced in comparison to that in histamine-competent mice. However, antagonists at H1R, H2R, and H3R do not provide an effect on inflammation, supporting the idea that H4R is responsible for the histamine effects. In the present review, we discuss the involvement of histamine and H4R in inflammatory and inflammation-associated diseases of the gut.
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18
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Seppälä TT, Latchford A, Negoi I, Sampaio Soares A, Jimenez‐Rodriguez R, Sánchez‐Guillén L, Evans DG, Ryan N, Crosbie EJ, Dominguez‐Valentin M, Burn J, Kloor M, von Knebel Doeberitz M, van Duijnhoven FJB, Quirke P, Sampson JR, Møller P, Möslein G, the European Hereditary Tumour Group (EHTG) and European Society of Coloproctology (ESCP). European guidelines from the EHTG and ESCP for Lynch syndrome: an updated third edition of the Mallorca guidelines based on gene and gender. Br J Surg 2021; 108:484-498. [PMID: 34043773 PMCID: PMC10364896 DOI: 10.1002/bjs.11902] [Citation(s) in RCA: 149] [Impact Index Per Article: 37.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Revised: 05/16/2020] [Accepted: 06/14/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Lynch syndrome is the most common genetic predisposition for hereditary cancer but remains underdiagnosed. Large prospective observational studies have recently increased understanding of the effectiveness of colonoscopic surveillance and the heterogeneity of cancer risk between genotypes. The need for gene- and gender-specific guidelines has been acknowledged. METHODS The European Hereditary Tumour Group (EHTG) and European Society of Coloproctology (ESCP) developed a multidisciplinary working group consisting of surgeons, clinical and molecular geneticists, pathologists, epidemiologists, gastroenterologists, and patient representation to conduct a graded evidence review. The previous Mallorca guideline format was used to revise the clinical guidance. Consensus for the guidance statements was acquired by three Delphi voting rounds. RESULTS Recommendations for clinical and molecular identification of Lynch syndrome, surgical and endoscopic management of Lynch syndrome-associated colorectal cancer, and preventive measures for cancer were produced. The emphasis was on surgical and gastroenterological aspects of the cancer spectrum. Manchester consensus guidelines for gynaecological management were endorsed. Executive and layperson summaries were provided. CONCLUSION The recommendations from the EHTG and ESCP for identification of patients with Lynch syndrome, colorectal surveillance, surgical management of colorectal cancer, lifestyle and chemoprevention in Lynch syndrome that reached a consensus (at least 80 per cent) are presented.
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Affiliation(s)
- T T Seppälä
- Department of Surgery, Helsinki University Hospital, and University of Helsinki, Helsinki, Finland
- Department of Surgical Oncology, Johns Hopkins Hospital, Baltimore Maryland, USA
| | - A Latchford
- Department of Cancer and Surgery, Imperial College London, UK
- St Mark's Hospital, London North West Healthcare NHS Trust, London, UK
| | - I Negoi
- Department of Surgery, Emergency Hospital of Bucharest, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | | | - R Jimenez‐Rodriguez
- Department of Surgery, Hospital Universitario Virgen del Rocío, Seville, Spain
| | - L Sánchez‐Guillén
- Colorectal Unit, Department of General Surgery, Elche University General Hospital Elche, Alicante, Spain
| | - D G Evans
- Manchester Centre for Genomic Medicine, Division of Evolution and Genomic Sciences, University of Manchester, Manchester University Hospitals NHS Foundation Trust, UK
| | - N Ryan
- Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, St Mary's Hospital, Manchester, UK
- Centre for Academic Women's Health, University of Bristol, Bristol, UK
| | - E J Crosbie
- Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, St Mary's Hospital, Manchester, UK
| | - M Dominguez‐Valentin
- Department of Tumour Biology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
| | - J Burn
- Faculty of Medical Sciences, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - M Kloor
- Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Germany
- Cooperation Unit Applied Tumour Biology, German Cancer Research Centre, Heidelberg, Germany
| | - M von Knebel Doeberitz
- Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Germany
- Cooperation Unit Applied Tumour Biology, German Cancer Research Centre, Heidelberg, Germany
| | - F J B van Duijnhoven
- Division of Human Nutrition and Health, Wageningen University and Research, Wageningen, the Netherlands
| | - P Quirke
- Pathology and Data Analytics, School of Medicine, University of Leeds, Leeds, UK
| | - J R Sampson
- Institute of Medical Genetics, Division of Cancer and Genetics, Cardiff University School of Medicine, Heath Park, Cardiff, UK
| | - P Møller
- Department of Tumour Biology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
- University of Witten/Herdecke, Witten, Germany
| | - G Möslein
- Centre for Hereditary Tumours, Bethesda Hospital, Duisburg, Germany
- University of Witten/Herdecke, Witten, Germany
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19
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Wang F, Song M, Lu X, Zhu X, Deng J. Gut microbes in gastrointestinal cancers. Semin Cancer Biol 2021; 86:967-975. [PMID: 33812983 DOI: 10.1016/j.semcancer.2021.03.037] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 03/26/2021] [Accepted: 03/29/2021] [Indexed: 02/06/2023]
Abstract
Gut microbes (GMs), dominated by bacteria, play important roles in many physiological processes. The structures and functions of GMs are closely related to human health, the occurrence and development of diseases and the rapid recovery of the body. Gastrointestinal cancers are the major diseases affecting human health worldwide. With the development of metagenomic technology and the wide application of new generation sequencing technology, a large number of studies suggest that complex GMs are related to the occurrence and development of gastrointestinal cancers. Fecal microbiota transplantation (FMT) and probiotics can treat and prevent the occurrence of gastrointestinal cancers. This article reviews the latest research progress of microbes in gastrointestinal cancers from the perspectives of the correlation, the influence mechanism and the application, so as to provide new directions for the prevention, early diagnosis and treatment of gastrointestinal cancers.
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Affiliation(s)
- Fei Wang
- Division of Gastroenterology, Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Meiyi Song
- Department of Gastroenterology and Hepatology, Institution of Digestive Diseases, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Xiya Lu
- Department of Gastroenterology and Hepatology, Institution of Digestive Diseases, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Xuefeng Zhu
- University of Shanghai for Science and Technology, Shanghai, China.
| | - Jiali Deng
- Regeneration and Ageing Lab, School of Life Science, Shanghai University, Shanghai, 200444, China.
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20
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Zhou E, Rifkin S. Colorectal Cancer and Diet: Risk Versus Prevention, Is Diet an Intervention? Gastroenterol Clin North Am 2021; 50:101-111. [PMID: 33518157 DOI: 10.1016/j.gtc.2020.10.012] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Colorectal cancer is the third most common cause of cancer in men and women in the world. Epidemiologic research approximates that half of colon cancer risk is preventable by modifiable risk factors, including diet. This article reviews prior studies involving certain food items and their relation to colorectal cancer, to elucidate whether diet can be a potential intervention.
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Affiliation(s)
- Elinor Zhou
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 431, Baltimore, MD, USA.
| | - Samara Rifkin
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Michigan School of Medicine, 1150 West Medical Center Drive, 6520 MSRB1, Ann Arbor, MI, USA
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21
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Affiliation(s)
- Dery Bede
- State Key Laboratory of Food Science and Technology Jiangnan University 1800 Luhu Avenue Wuxi Jiangsu Province 214122 P. R. China
| | - Lou Zaixiang
- State Key Laboratory of Food Science and Technology Jiangnan University 1800 Luhu Avenue Wuxi Jiangsu Province 214122 P. R. China
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Jiang TJ, Wang F, Wang YN, Hu JJ, Ding PR, Lin JZ, Pan ZZ, Chen G, Shao JY, Xu RH, Zhao Q, Wang F. Germline mutational profile of Chinese patients under 70 years old with colorectal cancer. Cancer Commun (Lond) 2020; 40:620-632. [PMID: 32914570 PMCID: PMC7668457 DOI: 10.1002/cac2.12093] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/28/2020] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Inherited susceptibility accounts for nearly one-third of colorectal cancer (CRC) predispositions and has an 80%-100% lifetime risk of this disease. However, there are few data about germline mutations of hereditary CRC-related genes in Chinese patients with CRC. This study aimed to assess the prevalence of gene mutations related to cancer susceptibility among Chinese patients with CRC, differences between Chinese and Western patients, and the phenotype-genotype correlation. METHODS We retrospectively collected tumor samples from 526 patients with CRC under 70 years old who underwent hereditary CRC genetic testing. A series of bioinformatic analyses, as well as statistical comparisons, were performed. RESULTS We found that 77 patients (14.6%) harbored functional variants of the 12 genes. The mutation frequencies of the top 5 mutated genes were 6.5% for MutL homolog 1 (MLH1), 5.1% for MutS homolog 2 (MSH2), 1.0% for MSH6, 0.8% for PMS1 homolog 2 (PMS2), and 0.8% for APC regulator of the WNT signaling pathway (APC). Our data showed much higher rates of mutations of MSH6 and PMS2 genes among all mismatch repair (MMR) genes as compared with those in Western populations. Mutations in MLH1, MSH2, and MSH6 were found to be mutually exclusive. Patients with MLH1 or MSH2 mutations had higher frequencies of personal history of cancer (MLH1: 20.6% vs. 8.7%; MSH2: 25.9% vs. 8.6%) and family history of cancer than those without these mutations (MLH1: 73.5% vs. 48.4%; MSH2: 70.4% vs. 48.9%), and the lesions were more prone to occur on the right side of the colon than on the left side (MLH1: 73.5% vs. 29.3%; MSH2: 56.0% vs. 31.0%). The proportion of stage I/II disease was higher in patients with MLH1 mutations than in those without MLH1 mutations (70.6% vs. 50.7%), and the rate of polyps was higher in patients with APC mutations than in those with wild-type APC (75.0% vs. 17.4%). CONCLUSION These results provide a full-scale landscape of hereditary susceptibility over 12 related genes in CRC patients and suggest that a comprehensive multi-gene panel testing for hereditary CRC predisposition could be a helpful analysis in clinical practice.
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Affiliation(s)
- Teng-Jia Jiang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China
| | - Fang Wang
- Department of Molecular Diagnosis, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China
| | - Ying-Nan Wang
- Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China
| | - Jia-Jia Hu
- Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China
| | - Pei-Rong Ding
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China
| | - Jun-Zhong Lin
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China
| | - Zhi-Zhong Pan
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China
| | - Gong Chen
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China
| | - Jian-Yong Shao
- Department of Molecular Diagnosis, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China
| | - Rui-Hua Xu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China
| | - Qi Zhao
- Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China
| | - Feng Wang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China
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23
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Burn J, Sheth H, Elliott F, Reed L, Macrae F, Mecklin JP, Möslein G, McRonald FE, Bertario L, Evans DG, Gerdes AM, Ho JWC, Lindblom A, Morrison PJ, Rashbass J, Ramesar R, Seppälä T, Thomas HJW, Pylvänäinen K, Borthwick GM, Mathers JC, Bishop DT. Cancer prevention with aspirin in hereditary colorectal cancer (Lynch syndrome), 10-year follow-up and registry-based 20-year data in the CAPP2 study: a double-blind, randomised, placebo-controlled trial. Lancet 2020; 395:1855-1863. [PMID: 32534647 PMCID: PMC7294238 DOI: 10.1016/s0140-6736(20)30366-4] [Citation(s) in RCA: 243] [Impact Index Per Article: 48.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Revised: 01/31/2020] [Accepted: 02/06/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND Lynch syndrome is associated with an increased risk of colorectal cancer and with a broader spectrum of cancers, especially endometrial cancer. In 2011, our group reported long-term cancer outcomes (mean follow-up 55·7 months [SD 31·4]) for participants with Lynch syndrome enrolled into a randomised trial of daily aspirin versus placebo. This report completes the planned 10-year follow-up to allow a longer-term assessment of the effect of taking regular aspirin in this high-risk population. METHODS In the double-blind, randomised CAPP2 trial, 861 patients from 43 international centres worldwide (707 [82%] from Europe, 112 [13%] from Australasia, 38 [4%] from Africa, and four [<1%] from The Americas) with Lynch syndrome were randomly assigned to receive 600 mg aspirin daily or placebo. Cancer outcomes were monitored for at least 10 years from recruitment with English, Finnish, and Welsh participants being monitored for up to 20 years. The primary endpoint was development of colorectal cancer. Analysis was by intention to treat and per protocol. The trial is registered with the ISRCTN registry, number ISRCTN59521990. FINDINGS Between January, 1999, and March, 2005, 937 eligible patients with Lynch syndrome, mean age 45 years, commenced treatment, of whom 861 agreed to be randomly assigned to the aspirin group or placebo; 427 (50%) participants received aspirin and 434 (50%) placebo. Participants were followed for a mean of 10 years approximating 8500 person-years. 40 (9%) of 427 participants who received aspirin developed colorectal cancer compared with 58 (13%) of 434 who received placebo. Intention-to-treat Cox proportional hazards analysis revealed a significantly reduced hazard ratio (HR) of 0·65 (95% CI 0·43-0·97; p=0·035) for aspirin versus placebo. Negative binomial regression to account for multiple primary events gave an incidence rate ratio of 0·58 (0·39-0·87; p=0·0085). Per-protocol analyses restricted to 509 who achieved 2 years' intervention gave an HR of 0·56 (0·34-0·91; p=0·019) and an incidence rate ratio of 0·50 (0·31-0·82; p=0·0057). Non-colorectal Lynch syndrome cancers were reported in 36 participants who received aspirin and 36 participants who received placebo. Intention-to-treat and per-protocol analyses showed no effect. For all Lynch syndrome cancers combined, the intention-to-treat analysis did not reach significance but per-protocol analysis showed significantly reduced overall risk for the aspirin group (HR=0·63, 0·43-0·92; p=0·018). Adverse events during the intervention phase between aspirin and placebo groups were similar, and no significant difference in compliance between intervention groups was observed for participants with complete intervention phase data; details reported previously. INTERPRETATION The case for prevention of colorectal cancer with aspirin in Lynch syndrome is supported by our results. FUNDING Cancer Research UK, European Union, MRC, NIHR, Bayer Pharma AG, Barbour Foundation.
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Affiliation(s)
- John Burn
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
| | - Harsh Sheth
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Faye Elliott
- Division of Haematology and Immunology, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK
| | - Lynn Reed
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Finlay Macrae
- Colorectal Medicine and Genetics, Royal Melbourne Hospital, Melbourne, Australia
| | - Jukka-Pekka Mecklin
- Department of Education & Research, Jyväskylä Central Hospital, Jyväskylä, Finland; Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland
| | | | - Fiona E McRonald
- National Cancer Registration and Analysis Service, Public Health England, London, UK
| | - Lucio Bertario
- Instituto Nazionale per lo Studio e, la Cura dei Tumori, Milan, Italy
| | - D Gareth Evans
- Division of Evolution and Genomic Medicine, University of Manchester, Manchester, UK; St Mary's Hospital, Manchester Universities Foundation Trust, Manchester, UK
| | | | - Judy W C Ho
- Hereditary GI Cancer Registry, Department of Surgery, Queen Mary Hospital, Hong Kong Special Administrative Region, China
| | - Annika Lindblom
- Department of Molecular Medicine & Surgery, Karolinska Institutet, Stockholm, Sweden
| | - Patrick J Morrison
- Department of Medical Genetics, Queens University Belfast, Belfast City Hospital HSC Trust, Belfast, UK
| | - Jem Rashbass
- National Cancer Registration and Analysis Service, Public Health England, London, UK
| | - Raj Ramesar
- Genomic and Precision Medicine Research Unit, Division of Human Genetics, Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, South Africa
| | - Toni Seppälä
- Department of Gastrointestinal Surgery, Helsinki University Hospital, Helsinki, Finland
| | - Huw J W Thomas
- St Mark's Hospital, London, UK; Faculty of Medicine, Imperial College London, London, UK
| | - Kirsi Pylvänäinen
- Department of Education & Research, Jyväskylä Central Hospital, Jyväskylä, Finland
| | - Gillian M Borthwick
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
| | - John C Mathers
- Human Nutrition Research Centre, Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK
| | - D Timothy Bishop
- Division of Haematology and Immunology, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK
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24
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Taniguchi F, Tanakaya K, Sugano K, Akagi K, Ishida H, Nagahisa S, Nishimura S, Une Y, Kimura Y, Watanabe M, Utsumi M, Aoki H. Adequacy evaluation of the annual colonoscopic surveillance and individual difference of disease phenotypes in Lynch syndrome. Jpn J Clin Oncol 2020; 50:635-642. [PMID: 32372090 DOI: 10.1093/jjco/hyaa006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Accepted: 01/09/2020] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Regular endoscopic surveillance for Lynch syndrome is reported to reduce colorectal cancer (CRC)-related mortality. However, the appropriate surveillance intervals are still unclear. We evaluated the adequacy of annual colonoscopy and investigated the differences in tumor occurrence rates between individual patients. METHODS In total, 25 patients with Lynch syndrome who underwent colonoscopic surveillance between 2007 and 2016 at the Iwakuni Clinical Center were included. We retrospectively investigated the surveillance frequency and the clinical features associated with tumor development. RESULTS Colonoscopic surveillance was performed every 397 days on average. A total of 101 tumors, including 8 intramucosal carcinomas and 15 carcinomas, were observed within the study period. Annual colonoscopy detected six malignancies, including a carcinoma requiring surgery. Tumor incidence was associated with tumor existence in the initial colonoscopies (P = 0.018). Patients with a tumor occurrence rate of 0.4 tumors per year during our observation period were significantly more likely to have malignancies detected during regular surveillance than patients who had a lower occurrence rate (P < 0.001). Malignancy occurrence rate was strongly associated with tumor occurrence rate (P < 0.001, R2 = 0.44). CONCLUSIONS Annual colonoscopic surveillance for Lynch syndrome patients was effective in reducing the risk of CRC progression, but was insufficient to completely avoid surgery. Because the tumor occurrence rate differed substantially between individuals, more intensive surveillance was required for high-risk patients.
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Affiliation(s)
- Fumitaka Taniguchi
- Department of Surgery, National Hospital Organization Iwakuni Clinical Center, Iwakuni, Japan
| | - Kohji Tanakaya
- Department of Surgery, National Hospital Organization Iwakuni Clinical Center, Iwakuni, Japan
| | - Kokichi Sugano
- Oncogene Research Unit/Cancer Prevention Unit, Tochigi Cancer Center, Utsunomiya, Japan
| | - Kiwamu Akagi
- Divisions of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center, Saitama, Japan
| | - Hideyuki Ishida
- Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan
| | - Seiichi Nagahisa
- Department of Surgery, National Hospital Organization Iwakuni Clinical Center, Iwakuni, Japan
| | - Seitaro Nishimura
- Department of Surgery, National Hospital Organization Iwakuni Clinical Center, Iwakuni, Japan
| | - Yuta Une
- Department of Surgery, National Hospital Organization Iwakuni Clinical Center, Iwakuni, Japan
| | - Yuji Kimura
- Department of Surgery, National Hospital Organization Iwakuni Clinical Center, Iwakuni, Japan
| | - Megumi Watanabe
- Department of Surgery, National Hospital Organization Iwakuni Clinical Center, Iwakuni, Japan
| | - Masashi Utsumi
- Department of Surgery, National Hospital Organization Iwakuni Clinical Center, Iwakuni, Japan
| | - Hideki Aoki
- Department of Surgery, National Hospital Organization Iwakuni Clinical Center, Iwakuni, Japan
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25
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Rao M, Gao C, Hou J, Gu J, Law BYK, Xu Y. Non-Digestible Carbohydrate and the Risk of Colorectal Neoplasia: A Systematic Review. Nutr Cancer 2020; 73:31-44. [PMID: 32202158 DOI: 10.1080/01635581.2020.1742360] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Non-digestible carbohydrate (NDC) is a fiber that can be fermented into short chain fatty acids (SCFAs) in gut, represented by resistant starch (RS) and inulin. Colorectal cancer (CRC) is one of the most common malignant cancer. Pre-clinical studies have reported that NDC can produce SCFAs to protect the gut epithelium, which is associated with prevention of CRC, but this role in clinical trails is controversial. In this review, we discusses whether RS and inulin should be offered to cancer/precancerous patients or healthy subjects to decrease their risk of CRC. A multiple database search was conducted for studies published on RS/inulin supplementation as a chemopreventive method from 1989 to 2019. The meta-analysis showed the total SCFAs and butyrate concentrations (P = 0.84; P = 0.79), and excretions (P = 0.55; P = 0.63) in feces did not increase significantly after RS/inulin supplementation. Only two studies reported that RS/inulin inhibit the proliferation of large bowel epithelial, whereas 15 studies showed that it does not decrease the risk of neoplasia. RS/inulin restored the promotion of tumor risk factors in two studies and did not in four studies. Notably, the other four studies showed that RS increases pro-tumorigenesis mechanisms. The clinical evidences consistently show that RS/inulin is ineffective for preventing colorectal neoplasia.
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Affiliation(s)
- Mingyue Rao
- State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China.,Department of Oncology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.,Luzhou Key Laboratory of Cardiovascular and Metabolic Diseases, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
| | - Chenlin Gao
- State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China.,Luzhou Key Laboratory of Cardiovascular and Metabolic Diseases, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.,Department of Endocrinology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
| | - Jing Hou
- State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China
| | - Junling Gu
- State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China
| | - Betty Yuen Kwan Law
- State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China
| | - Yong Xu
- State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China.,Luzhou Key Laboratory of Cardiovascular and Metabolic Diseases, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.,Department of Endocrinology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
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26
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Baked Bread Enhances the Immune Response and the Catabolism in the Human Body in Comparison with Steamed Bread. Nutrients 2019; 12:nu12010001. [PMID: 31861252 PMCID: PMC7019488 DOI: 10.3390/nu12010001] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Revised: 12/09/2019] [Accepted: 12/16/2019] [Indexed: 12/02/2022] Open
Abstract
It is unclear whether different processing methods change the biological functions of foods and how these functions are evaluated in the human body. Here, steamed bread and baked bread, the traditional staple foods in China and many Western countries, were made by steaming and baking, respectively, using one piece of fermented wheat dough and then consumed by 16 healthy young volunteers. By detecting 38 cytokines, 12 metabolic enzymes, glucose, lactate, and nicotinamide adenine dinucleotide (NADH) in the serum, the cytokine network and central metabolic pathway network were investigated to compare the effects of the two staple foods on immunity and metabolism. Compared with steamed bread, baked bread increased (p < 0.05) concentrations of fractalkine and macrophage-derived chemokine, decreased (p < 0.05) the concentration of interleukin-1RA, increased (p < 0.05) the expression level of phosphofructokinase, and decreased (p < 0.05) the expression level of glucose-6-phosphate dehydrogenase in the serum. Two network analyses indicated that baked bread, as compared to the steamed bread, enhanced communication between immune cells, increased catabolism, and decreased anabolism. Further, a correlation analysis of cytokines and metabolic enzymes suggested that the two staple foods may affect metabolism by regulating the secretion of cytokines. These findings highlight how the same raw food material processed by different methods may have different impacts on immunity and metabolism in humans.
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27
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Pellat A, Netter J, Perkins G, Cohen R, Coulet F, Parc Y, Svrcek M, Duval A, André T. [Lynch syndrome: What is new?]. Bull Cancer 2019; 106:647-655. [PMID: 30527816 DOI: 10.1016/j.bulcan.2018.10.009] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2018] [Accepted: 10/02/2018] [Indexed: 12/17/2022]
Abstract
Lynch syndrome is a genetic condition defined by a germline mutation of an MMR (MisMatch Repair) gene leading to a defective DNA MMR system. Therefore, it is characterized by the predisposition to a spectrum of cancers, primarily colorectal cancer (CRC) and endometrial cancer (EC). Lynch syndrome-related CRC accounts for 3% of all CRC. Lynch syndrome also accounts for 2% of all EC. In case of Lynch syndrome, there is usually a familial history of cancer defined by the Amsterdam and Bethesda criteria. Diagnosis is made by tumor testing with (i) MMR immunohistochemistry and (ii) PCR for MSI (microsatellite instability), a genetic phenotype that characterizes these tumors. MSI can also be detected in sporadic tumors, through epigenetic events inactivating the MMR system. Progress in diagnosis and molecular biology has allowed for better identification of Lynch patients but also other rare genetic syndromes. MSI tumors can now benefit from new treatments such as immunotherapy which underlines the importance of their diagnosis. Finally, patients with Lynch syndrome as well as their relatives, undergo specific surveillance in order to prevent development of other cancers. This review will summarize the different aspects of Lynch syndrome and also focus on recent progress on the topic.
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Affiliation(s)
- Anna Pellat
- AP-HP, Sorbonne université, hôpital Saint-Antoine, et service d'oncologie médicale, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France.
| | - Jeanne Netter
- AP-HP, hôpital Tenon, service de gastro entérologie, 4, rue de la Chine, 75020 Paris, France
| | - Géraldine Perkins
- AP-HP, hôpital européen Georges Pompidou, unité d'oncogénétique, 20, rue Leblanc, 75015 Paris, France
| | - Romain Cohen
- AP-HP, Sorbonne université, hôpital Saint-Antoine, et service d'oncologie médicale, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France; Sorbonne université, unité Mixte de Recherche Scientifique 938 et SIRIC CURAMUS, Centre de recherche Saint-Antoine, équipe instabilité des microsatellites et cancer, équipe labellisée par la Ligue Nationale contre le cancer, Inserm, 75012 Paris, France
| | - Florence Coulet
- AP-HP, hôpitaux universitaire Pitié Salpêtrière-Charles, département de génétique, 47-83, boulevard de l'Hôpital, 75013 Paris, France
| | - Yann Parc
- AP-HP, Sorbonne université, hôpital Saint-Antoine, service de chirurgie générale et digestive, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France
| | - Magali Svrcek
- Sorbonne université, unité Mixte de Recherche Scientifique 938 et SIRIC CURAMUS, Centre de recherche Saint-Antoine, équipe instabilité des microsatellites et cancer, équipe labellisée par la Ligue Nationale contre le cancer, Inserm, 75012 Paris, France; AP-HP, hôpital Saint-Antoine, Sorbonne université et service d'anatomopathologie, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France
| | - Alex Duval
- Sorbonne université, unité Mixte de Recherche Scientifique 938 et SIRIC CURAMUS, Centre de recherche Saint-Antoine, équipe instabilité des microsatellites et cancer, équipe labellisée par la Ligue Nationale contre le cancer, Inserm, 75012 Paris, France
| | - Thierry André
- AP-HP, Sorbonne université, hôpital Saint-Antoine, et service d'oncologie médicale, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France; Sorbonne université, unité Mixte de Recherche Scientifique 938 et SIRIC CURAMUS, Centre de recherche Saint-Antoine, équipe instabilité des microsatellites et cancer, équipe labellisée par la Ligue Nationale contre le cancer, Inserm, 75012 Paris, France
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Anderson AS, Caswell S, Mowat C, Strachan JA, Steele RJC. Lifestyle in patients at increased risk of colorectal cancer. J Hum Nutr Diet 2019; 32:570-577. [DOI: 10.1111/jhn.12663] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Affiliation(s)
- A. S. Anderson
- Centre for Research into Cancer Prevention and Screening Cancer Research Division Ninewells Hospital & Medical School Dundee UK
| | - S. Caswell
- Centre for Research into Cancer Prevention and Screening Cancer Research Division Ninewells Hospital & Medical School Dundee UK
| | - C. Mowat
- Department of Gastroenterology Ninewells Hospital Dundee UK
| | | | - R. J. C. Steele
- Centre for Research into Cancer Prevention and Screening Cancer Research Division Ninewells Hospital & Medical School Dundee UK
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29
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Thanikachalam K, Khan G. Colorectal Cancer and Nutrition. Nutrients 2019; 11:nu11010164. [PMID: 30646512 PMCID: PMC6357054 DOI: 10.3390/nu11010164] [Citation(s) in RCA: 467] [Impact Index Per Article: 77.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Revised: 01/10/2019] [Accepted: 01/10/2019] [Indexed: 12/13/2022] Open
Abstract
Colorectal Cancer is the third most common cancer diagnosed in the US. While the incidence and the mortality rate of colorectal cancer has decreased due to effective cancer screening measures, there has been an increase in number of young patients diagnosed in colon cancer due to unclear reasons at this point of time. While environmental and genetic factors play a major role in the pathogenesis of colon cancer, extensive research has suggested that nutrition may play both a causal and protective role in the development of colon cancer. In this review article, we aim to provide a review of factors that play a major role in development of colorectal cancer.
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Affiliation(s)
- Kannan Thanikachalam
- Department of Hematology/Oncology, Henry Ford Health System, Detroit, MI 48202, USA.
| | - Gazala Khan
- Department of Hematology/Oncology, Henry Ford Health System, Detroit, MI 48202, USA.
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30
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Costea T, Hudiță A, Ciolac OA, Gălățeanu B, Ginghină O, Costache M, Ganea C, Mocanu MM. Chemoprevention of Colorectal Cancer by Dietary Compounds. Int J Mol Sci 2018; 19:E3787. [PMID: 30487390 PMCID: PMC6321468 DOI: 10.3390/ijms19123787] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Revised: 11/18/2018] [Accepted: 11/23/2018] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer is one of the leading causes of death, and the third most diagnosed type of cancer, worldwide. It is most common amongst men and women over 50 years old. Risk factors include smoking, alcohol, diet, physical inactivity, genetics, alterations in gut microbiota, and associated pathologies (diabetes, obesity, chronic inflammatory bowel diseases). This review will discuss, in detail, the chemopreventive properties of some dietary compounds (phenolic compounds, carotenoids, iridoids, nitrogen compounds, organosulfur compounds, phytosterols, essential oil compounds, polyunsaturated fatty acids and dietary fiber) against colorectal cancer. We present recent data, focusing on in vitro, laboratory animals and clinical trials with the previously mentioned compounds. The chemopreventive properties of the dietary compounds involve multiple molecular and biochemical mechanisms of action, such as inhibition of cell growth, inhibition of tumor initiation, inhibition of adhesion, migration and angiogenesis, apoptosis, interaction with gut microbiota, regulation of cellular signal transduction pathways and xenobiotic metabolizing enzymes, etc. Moreover, this review will also focus on the natural dietary compounds' bioavailability, their synergistic protective effect, as well as the association with conventional therapy. Dietary natural compounds play a major role in colorectal chemoprevention and continuous research in this field is needed.
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Affiliation(s)
- Teodora Costea
- Department of Pharmacognosy, Phytochemistry and Phytotherapy, "Carol Davila" University of Medicine and Pharmacy, 020956 Bucharest, Romania.
| | - Ariana Hudiță
- Department of Biochemistry and Molecular Biology, University of Bucharest, 050095 Bucharest, Romania.
| | - Oana-Alina Ciolac
- Department of Biophysics, "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania.
| | - Bianca Gălățeanu
- Department of Biochemistry and Molecular Biology, University of Bucharest, 050095 Bucharest, Romania.
| | - Octav Ginghină
- Department of Surgery, "Sf. Ioan" Emergency Clinical Hospital, 042122 Bucharest, Romania.
- Department II, Faculty of Dental Medicine, "Carol Davila" University of Medicine and Pharmacy, 030167 Bucharest, Romania.
| | - Marieta Costache
- Department of Biochemistry and Molecular Biology, University of Bucharest, 050095 Bucharest, Romania.
| | - Constanța Ganea
- Department of Biophysics, "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania.
| | - Maria-Magdalena Mocanu
- Department of Biophysics, "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania.
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31
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Insights Into the Relationship Between Gut Microbiota and Colorectal Cancer. CURRENT COLORECTAL CANCER REPORTS 2018. [DOI: 10.1007/s11888-018-0419-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Meenu M, Xu B. A critical review on anti-diabetic and anti-obesity effects of dietary resistant starch. Crit Rev Food Sci Nutr 2018; 59:3019-3031. [DOI: 10.1080/10408398.2018.1481360] [Citation(s) in RCA: 65] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Maninder Meenu
- Food Science and Technology Program, Beijing Normal University-Hong Kong Baptist University United International College, Zhuhai, China
| | - Baojun Xu
- Food Science and Technology Program, Beijing Normal University-Hong Kong Baptist University United International College, Zhuhai, China
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Boland PM, Yurgelun MB, Boland CR. Recent progress in Lynch syndrome and other familial colorectal cancer syndromes. CA Cancer J Clin 2018; 68:217-231. [PMID: 29485237 PMCID: PMC5980692 DOI: 10.3322/caac.21448] [Citation(s) in RCA: 112] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Revised: 01/08/2018] [Accepted: 01/31/2018] [Indexed: 12/16/2022] Open
Abstract
The current understanding of familial colorectal cancer was limited to descriptions of affected pedigrees until the early 1990s. A series of landscape-altering discoveries revealed that there were distinct forms of familial cancer, and most were related to genes previously not known to be involved in human disease. This review largely focuses on advances in our understanding of Lynch syndrome because of the unique relationship of this disease to defective DNA mismatch repair and the clinical implications this has for diagnostics, prevention, and therapy. Recent advances have occurred in our understanding of the epidemiology of this disease, and the advent of broad genetic panels has altered the approach to germline and somatic diagnoses for all of the familial colorectal cancer syndromes. Important advances have been made toward a more complete mechanistic understanding of the pathogenesis of neoplasia in the setting of Lynch syndrome, and these advances have important implications for prevention. Finally, paradigm-shifting approaches to treatment of Lynch-syndrome and related tumors have occurred through the development of immune checkpoint therapies for hypermutated cancers. CA Cancer J Clin 2018;68:217-231. © 2018 American Cancer Society.
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Affiliation(s)
- Patrick M Boland
- Assistant Professor, Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY
| | - Matthew B Yurgelun
- Assistant Professor of Medicine, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA
| | - C Richard Boland
- Professor, Department of Medicine, University of California at San Diego School of Medicine, San Diego, CA
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Wang Q, Wang P, Xiao Z. Resistant starch prevents tumorigenesis of dimethylhydrazine-induced colon tumors via regulation of an ER stress-mediated mitochondrial apoptosis pathway. Int J Mol Med 2018; 41:1887-1898. [PMID: 29393371 PMCID: PMC5810243 DOI: 10.3892/ijmm.2018.3423] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2016] [Accepted: 01/12/2018] [Indexed: 12/11/2022] Open
Abstract
Resistant starch is as common soluble fiber that escapes digestion in the small intestine and can regulate intestinal function, metabolism of blood glucose and lipids, and may prevent tumorigenesis of gastrointestinal cancer. Epidemiology and other evidence have suggested that resistant starch may prevent colon cancer development. The aim of the current study was to explore the ameliorative effects and potential mechanisms of resistant starch in the tumorigenesis of colon tumors induced by dimethylhydrazine in C57BL/6 mice. Western blot analysis, ELISA, microscopy, immunofluorescence and immunohistochemistry were used to analyze the efficacy of resistant starch on the metabolic balance in the colon and tumorigenesis of colon tumors. The results demonstrated that a diet containing resistant starch decreased the animal body weight and reduced free ammonia, pH and short chain fatty acids in feces compared with mice that received a standard diet. Resistant starch reduced the incidence of colon tumors and suppressed the expression of carcinogenesis-associated proteins, including heat shock protein 25, protein kinase C-d and gastrointestinal glutathione peroxidase in colon epithelial cells compared with standard starch and control groups. Colon tumor cells proliferation and dedifferentiation were significantly decreased by a resistant starch diet. The results also demonstrated that resistant starch increased the apoptosis of colon tumor cells through regulation of apoptosis-associated gene expression levels in colon tumor cells. Oxidative stress and endoplasmic reticulum stress were upregulated, and elevation eukaryotic translation initiation factor 2α (eIF2α), activating transcription factor-4 and secretase-β expression levels were increased in the resistant starch diet group. Additionally, the activity of eIF2α and PERK were increased in colon tumor cells from mice that had received resistant starch. Increasing DNA damage-inducible transcript 3 protein (CHOP), binding immunoglobulin protein (BIP) and caspase-12 expression levels upregulated by resistant starch diet may contribute to the resistant starch-induced apoptosis of colon tumor cells induced by 1,2-dimethylhydrazine. In vitro assays demonstrated that knockdown of eIF2α inhibited apoptosis of colon tumor cells isolated from mice fed with resistant starch, which also downregulated CHOP, BIP and caspase-3 expression levels compared with controls. Furthermore, long-term survival of experimental mice was prolonged by the resistant starch diet compared with the standard diet group. In conclusion, the results indicate that resistant starch in the diet may prevent carcinogenesis of colon epithelial cells, mediated by enhancing apoptosis through an endoplasmic reticulum stress-mediated mitochondrial apoptosis pathway.
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Affiliation(s)
- Qiuyu Wang
- College of Food Science, Northeast Agricultural University, Harbin, Heilongjiang 150030, P.R. China
| | - Peng Wang
- College of Food Science, Northeast Agricultural University, Harbin, Heilongjiang 150030, P.R. China
| | - Zhigang Xiao
- College of Food Science, Northeast Agricultural University, Harbin, Heilongjiang 150030, P.R. China
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Maida M, Macaluso FS, Ianiro G, Mangiola F, Sinagra E, Hold G, Maida C, Cammarota G, Gasbarrini A, Scarpulla G. Screening of colorectal cancer: present and future. Expert Rev Anticancer Ther 2017; 17:1131-1146. [PMID: 29022408 DOI: 10.1080/14737140.2017.1392243] [Citation(s) in RCA: 120] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Colorectal cancer (CRC) is the third most common cancer in males and second in females, and the fourth most common cause of cancer death worldwide. Currently, about 60-70% of diagnosed cases in symptomatic patients are detected at an advanced stage of disease. Earlier stage detection through the use of screening strategies would allow for better outcomes in terms of reducing the disease burden. Areas covered: The aim of this paper is to review the current published evidence from literature which assesses the performance and effectiveness of different screening tests for the early detection of CRC. Expert commentary: Adequate screening strategies can reduce CRC incidence and mortality. In the last few decades, several tests have been proposed for CRC screening. To date, there is still insufficient evidence to identify which approach is definitively superior, and no screening strategy for CRC can therefore be defined as universally ideal. The best strategy would be the one that can be economically viable and to which the patient can adhere best to over time. The latest guidelines suggest colonoscopy every 10 years or annual fecal immuno-chemical test (FIT) for people with normal risk, while for individuals with high risk or hereditary syndromes specific recommendations are provided.
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Affiliation(s)
- Marcello Maida
- a Section of Gastroenterology , S.Elia - Raimondi Hospital , Caltanissetta , Italy
| | | | - Gianluca Ianiro
- c Internal Medicine, Gastroenterology & Liver Unit , Università Cattolica Sacro Cuore , Rome , Italy
| | - Francesca Mangiola
- c Internal Medicine, Gastroenterology & Liver Unit , Università Cattolica Sacro Cuore , Rome , Italy
| | - Emanuele Sinagra
- d Gastroenterology and Endoscopy Unit , Fondazione Istituto San Raffaele Giglio , Cefalù , Italy
| | - Georgina Hold
- e School of Medicine, Medical Sciences and Nutrition , University of Aberdeen , Aberdeen , UK
| | - Carlo Maida
- f Section of Internal Medicine , DIBIMIS, University of Palermo , Palermo , Italy
| | - Giovanni Cammarota
- c Internal Medicine, Gastroenterology & Liver Unit , Università Cattolica Sacro Cuore , Rome , Italy
| | - Antonio Gasbarrini
- c Internal Medicine, Gastroenterology & Liver Unit , Università Cattolica Sacro Cuore , Rome , Italy
| | - Giuseppe Scarpulla
- a Section of Gastroenterology , S.Elia - Raimondi Hospital , Caltanissetta , Italy
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van der Beek CM, Dejong CHC, Troost FJ, Masclee AAM, Lenaerts K. Role of short-chain fatty acids in colonic inflammation, carcinogenesis, and mucosal protection and healing. Nutr Rev 2017; 75:286-305. [PMID: 28402523 DOI: 10.1093/nutrit/nuw067] [Citation(s) in RCA: 243] [Impact Index Per Article: 30.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Short-chain fatty acids (SCFAs), mainly acetate, propionate, and butyrate, produced by microbial fermentation of undigested food substances are believed to play a beneficial role in human gut health. Short-chain fatty acids influence colonic health through various mechanisms. In vitro and ex vivo studies show that SCFAs have anti-inflammatory and anticarcinogenic effects, play an important role in maintaining metabolic homeostasis in colonocytes, and protect colonocytes from external harm. Animal studies have found substantial positive effects of SCFAs or dietary fiber on colonic disease, but convincing evidence in humans is lacking. Most human intervention trials have been conducted in the context of inflammatory bowel disease. Only a limited number of those trials are of high quality, showing little or no favorable effect of SCFA treatment over placebo. Opportunities for future research include exploring the use of combination therapies with anti-inflammatory drugs, prebiotics, or probiotics; the use of prodrugs in the setting of carcinogenesis; or the direct application of SCFAs to improve mucosal healing after colonic surgery.
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Affiliation(s)
- Christina M van der Beek
- C.M. van der Beek, C.H.C. Dejong, F.J. Troost, A.A.M. Masclee, and K. Lenaerts are with Top Institute Food and Nutrition, Wageningen, the Netherlands. C.M. van der Beek, C.H.C. Dejong, and K. Lenaerts are with the Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, the Netherlands. C.H.C. Dejong is with the School for Oncology and Developmental Biology (GROW), Maastricht University Medical Center+, Maastricht, the Netherlands. F.J. Troost and A.A.M. Masclee are with the Department of Internal Medicine, Division of Gastroenterology-Hepatology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, the Netherlands
| | - Cornelis H C Dejong
- C.M. van der Beek, C.H.C. Dejong, F.J. Troost, A.A.M. Masclee, and K. Lenaerts are with Top Institute Food and Nutrition, Wageningen, the Netherlands. C.M. van der Beek, C.H.C. Dejong, and K. Lenaerts are with the Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, the Netherlands. C.H.C. Dejong is with the School for Oncology and Developmental Biology (GROW), Maastricht University Medical Center+, Maastricht, the Netherlands. F.J. Troost and A.A.M. Masclee are with the Department of Internal Medicine, Division of Gastroenterology-Hepatology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, the Netherlands
| | - Freddy J Troost
- C.M. van der Beek, C.H.C. Dejong, F.J. Troost, A.A.M. Masclee, and K. Lenaerts are with Top Institute Food and Nutrition, Wageningen, the Netherlands. C.M. van der Beek, C.H.C. Dejong, and K. Lenaerts are with the Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, the Netherlands. C.H.C. Dejong is with the School for Oncology and Developmental Biology (GROW), Maastricht University Medical Center+, Maastricht, the Netherlands. F.J. Troost and A.A.M. Masclee are with the Department of Internal Medicine, Division of Gastroenterology-Hepatology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, the Netherlands
| | - Ad A M Masclee
- C.M. van der Beek, C.H.C. Dejong, F.J. Troost, A.A.M. Masclee, and K. Lenaerts are with Top Institute Food and Nutrition, Wageningen, the Netherlands. C.M. van der Beek, C.H.C. Dejong, and K. Lenaerts are with the Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, the Netherlands. C.H.C. Dejong is with the School for Oncology and Developmental Biology (GROW), Maastricht University Medical Center+, Maastricht, the Netherlands. F.J. Troost and A.A.M. Masclee are with the Department of Internal Medicine, Division of Gastroenterology-Hepatology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, the Netherlands
| | - Kaatje Lenaerts
- C.M. van der Beek, C.H.C. Dejong, F.J. Troost, A.A.M. Masclee, and K. Lenaerts are with Top Institute Food and Nutrition, Wageningen, the Netherlands. C.M. van der Beek, C.H.C. Dejong, and K. Lenaerts are with the Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, the Netherlands. C.H.C. Dejong is with the School for Oncology and Developmental Biology (GROW), Maastricht University Medical Center+, Maastricht, the Netherlands. F.J. Troost and A.A.M. Masclee are with the Department of Internal Medicine, Division of Gastroenterology-Hepatology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, the Netherlands
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The anti-tumor effect of aspirin: What we know and what we expect. Biomed Pharmacother 2017; 95:656-661. [DOI: 10.1016/j.biopha.2017.08.085] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2017] [Revised: 08/19/2017] [Accepted: 08/23/2017] [Indexed: 12/12/2022] Open
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Fardet A, Druesne-Pecollo N, Touvier M, Latino-Martel P. Do alcoholic beverages, obesity and other nutritional factors modify the risk of familial colorectal cancer? A systematic review. Crit Rev Oncol Hematol 2017; 119:94-112. [PMID: 28927785 DOI: 10.1016/j.critrevonc.2017.09.001] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2017] [Revised: 07/28/2017] [Accepted: 09/06/2017] [Indexed: 12/16/2022] Open
Abstract
PURPOSE Individuals with family history of colorectal cancer are at higher risk of colorectal cancer than the general population. Until now, guidelines for familial colorectal cancer risk have only pointed at early diagnosis efforts via screening tests and surveillance, and payed scarce or no attention to lowering exposure to modifiable risk factors, notably nutritional factors. METHODS We conducted a systematic review of epidemiological studies investigating the associations between nutritional factors, family history of colorectal cancer, and colorectal cancer risk. From the 5312 abstracts identified until December 2016, 184 full text articles were examined for eligibility. Finally, 31 articles (21 from case-control studies, 9 from cohort studies and 1 from an intervention study) met inclusion criteria and were analyzed. RESULTS Mainly, the combinations of family history of colorectal cancer and higher consumptions of alcoholic beverages, red or processed meat, or overweight/obesity increase the risk of colorectal cancer. Consistently, a strong increase is observed with the combinations of family history of colorectal cancer and unhealthy dietary patterns/lifestyles. Statistically significant interactions between these nutritional factors, family history of colorectal cancer and colorectal cancer risk are reported. Other data are inconclusive and additional prospective studies are needed. CONCLUSIONS For the first time, our findings highlight that addressing high consumption of alcoholic beverages, red or processed meat, and overweight/obesity, and more largely the exposure to multiple unhealthy dietary/nutritional behaviors could offer new perspectives of prevention to individuals with family history of colorectal cancer. A better information of these patients and of health professionals on these nutritional modifiable risk factors is recommended.
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Affiliation(s)
- Anthony Fardet
- INRA, UMR 1019, UNH, CRNH Auvergne, F-63000 Clermont-Ferrand & Clermont University, University of Auvergne, Human Nutrition Unit, BP 10448, F-63000 Clermont-Ferrand, France
| | - Nathalie Druesne-Pecollo
- Sorbonne Paris Cité Epidemiology and Statistics Research Centre (CRESS), Inserm U1153, Inra U1125, Cnam, Nutritional Epidemiology Research Team (EREN), Bobigny, France; French Network for Nutrition and Cancer Research (NACRe Network), France
| | - Mathilde Touvier
- Sorbonne Paris Cité Epidemiology and Statistics Research Centre (CRESS), Inserm U1153, Inra U1125, Cnam, Nutritional Epidemiology Research Team (EREN), Bobigny, France; French Network for Nutrition and Cancer Research (NACRe Network), France
| | - Paule Latino-Martel
- Sorbonne Paris Cité Epidemiology and Statistics Research Centre (CRESS), Inserm U1153, Inra U1125, Cnam, Nutritional Epidemiology Research Team (EREN), Bobigny, France; French Network for Nutrition and Cancer Research (NACRe Network), France.
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Wang H, Pang G. Effect of resistant and digestible rice starches on human cytokine and lactate metabolic networks in serum. Cytokine 2017; 93:57-65. [PMID: 28511942 DOI: 10.1016/j.cyto.2017.05.009] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2016] [Revised: 02/27/2017] [Accepted: 05/09/2017] [Indexed: 11/18/2022]
Abstract
Resistant starch generated after treating ordinary starch is of great significance to human health in the countries with overnutrition. However, its functional evaluation in the human body has been rarely reported. By determining the lactate metabolic flux, 12 serum enzymes expression level and 38 serum cytokines in healthy volunteers, the variation in cytokine network and lactate metabolic network in serum were investigated to compare the mechanism of the physiological effects between the two starches. The results indicated that compared with digestible starch, resistant starch had anti-inflammatory effects, increased anabolism, and decreased catabolism. Further, the intercellular communication networks including cytokine and lactate metabolic networks were mapped out. The relationship suggested that resistant starch might affect and control the secretion of cytokines to regulate lactate metabolic network in the body, promoting the development of immunometabolism.
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Affiliation(s)
- Huisong Wang
- Tianjin Key Laboratory of Food Biotechnology, College of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China
| | - Guangchang Pang
- Tianjin Key Laboratory of Food Biotechnology, College of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China.
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Malcomson FC, Willis ND, McCallum I, Xie L, Ibero-Baraibar I, Leung WC, Kelly S, Bradburn DM, Belshaw NJ, Johnson IT, Mathers JC. Effects of supplementation with nondigestible carbohydrates on fecal calprotectin and on epigenetic regulation of SFRP1 expression in the large-bowel mucosa of healthy individuals. Am J Clin Nutr 2017; 105:400-410. [PMID: 28077379 PMCID: PMC5267298 DOI: 10.3945/ajcn.116.135657] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2016] [Accepted: 12/05/2016] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Hyperactive Wnt signaling is frequently observed in colorectal cancer. Higher intakes of dietary fiber [nondigestible carbohydrates (NDCs)] and the fermentation product butyrate are protective against colorectal cancer and may exert their preventative effects via modulation of the Wnt pathway. OBJECTIVES We investigated the effects of supplementing healthy individuals with 2 NDCs [resistant starch (RS) and polydextrose] on fecal calprotectin concentrations and Wnt pathway-related gene expression. In addition, we determined whether effects on secreted frizzled-related protein 1 (SFRP1) expression are mediated via the epigenetic mechanisms DNA methylation and microRNA expression. DESIGN In a randomized, double-blind, placebo-controlled trial (the Dietary Intervention, Stem cells and Colorectal Cancer (DISC) Study), 75 healthy participants were supplemented with RS and/or polydextrose or placebo for 50 d in a 2 × 2 factorial design. Pre- and postintervention stool samples and rectal mucosal biopsies were collected and used to quantify calprotectin and expression of 12 Wnt-related genes, respectively. The expression of 10 microRNAs predicted to target SFRP1 was also quantified by quantitative reverse transcriptase-polymerase chain reaction, and DNA methylation was quantified at 7 CpG sites within the SFRP1 promoter region by pyrosequencing. RESULTS NDC supplementation did not affect fecal calprotectin concentration. SFRP1 mRNA expression was reduced by both RS (P = 0.005) and polydextrose (P = 0.053). RS and polydextrose did not affect SFRP1 methylation or alter the expression of 10 microRNAs predicted to target SFRP1. There were no significant interactions between RS and polydextrose. CONCLUSIONS RS and polydextrose supplementation did not affect fecal calprotectin concentrations. Downregulation of SFRP1 with RS and polydextrose could result in increased Wnt pathway activity. However, effects on Wnt pathway activity and downstream functional effects in the healthy large-bowel mucosa remain to be investigated. The DISC Study was registered at clinicaltrials.gov as NCT01214681.
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Affiliation(s)
- Fiona C Malcomson
- Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, United Kingdom
| | - Naomi D Willis
- Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, United Kingdom
| | - Iain McCallum
- Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, United Kingdom
| | - Long Xie
- Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, United Kingdom
| | - Idoia Ibero-Baraibar
- Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, United Kingdom
| | - Wing C Leung
- Institute of Food Research, Norwich Research Park, Norwich, Norfolk, United Kingdom
| | - Seamus Kelly
- Northumbria Healthcare National Health Service Foundation Trust, North Shields, United Kingdom; and
| | - D Michael Bradburn
- Northumbria Healthcare National Health Service Foundation Trust, Ashington, United Kingdom
| | - Nigel J Belshaw
- Institute of Food Research, Norwich Research Park, Norwich, Norfolk, United Kingdom
| | - Ian T Johnson
- Institute of Food Research, Norwich Research Park, Norwich, Norfolk, United Kingdom
| | - John C Mathers
- Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, United Kingdom;
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Yao Y, Suo T, Andersson R, Cao Y, Wang C, Lu J, Chui E, Cochrane Colorectal Cancer Group. Dietary fibre for the prevention of recurrent colorectal adenomas and carcinomas. Cochrane Database Syst Rev 2017; 1:CD003430. [PMID: 28064440 PMCID: PMC6465195 DOI: 10.1002/14651858.cd003430.pub2] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND This is an update of the Cochrane review published in 2002.Colorectal cancer (CRC) is a major cause of morbidity and mortality in industrialised countries. Experimental evidence has supported the hypothesis that dietary fibre may protect against the development of CRC, although epidemiologic data have been inconclusive. OBJECTIVES To assess the effect of dietary fibre on the recurrence of colorectal adenomatous polyps in people with a known history of adenomatous polyps and on the incidence of CRC compared to placebo. Further, to identify the reported incidence of adverse effects, such as abdominal pain or diarrhoea, that resulted from the fibre intervention. SEARCH METHODS We identified randomised controlled trials (RCTs) from Cochrane Colorectal Cancer's Specialised Register, CENTRAL, MEDLINE and Embase (search date, 4 April 2016). We also searched ClinicalTrials.gov and WHO International Trials Registry Platform on October 2016. SELECTION CRITERIA We included RCTs or quasi-RCTs. The population were those having a history of adenomatous polyps, but no previous history of CRC, and repeated visualisation of the colon/rectum after at least two-years' follow-up. Dietary fibre was the intervention. The primary outcomes were the number of participants with: 1. at least one adenoma, 2. more than one adenoma, 3. at least one adenoma greater than or equal to 1 cm, or 4. a new diagnosis of CRC. The secondary outcome was the number of adverse events. DATA COLLECTION AND ANALYSIS Two reviewers independently extracted data, assessed trial quality and resolved discrepancies by consensus. We used risk ratios (RR) and risk difference (RD) with 95% confidence intervals (CI) to measure the effect. If statistical significance was reached, we reported the number needed to treat for an additional beneficial outcome (NNTB) or harmful outcome (NNTH). We combined the study data using the fixed-effect model if it was clinically, methodologically, and statistically reasonable. MAIN RESULTS We included seven studies, of which five studies with 4798 participants provided data for analyses in this review. The mean ages of the participants ranged from 56 to 66 years. All participants had a history of adenomas, which had been removed to achieve a polyp-free colon at baseline. The interventions were wheat bran fibre, ispaghula husk, or a comprehensive dietary intervention with high fibre whole food sources alone or in combination. The comparators were low-fibre (2 to 3 g per day), placebo, or a regular diet. The combined data showed no statistically significant difference between the intervention and control groups for the number of participants with at least one adenoma (5 RCTs, n = 3641, RR 1.04, 95% CI 0.95 to 1.13, low-quality evidence), more than one adenoma (2 RCTs, n = 2542, RR 1.06, 95% CI 0.94 to 1.20, low-quality evidence), or at least one adenoma 1 cm or greater (4 RCTs, n = 3224, RR 0.99, 95% CI 0.82 to 1.20, low-quality evidence) at three to four years. The results on the number of participants diagnosed with colorectal cancer favoured the control group over the dietary fibre group (2 RCTS, n = 2794, RR 2.70, 95% CI 1.07 to 6.85, low-quality evidence). After 8 years of comprehensive dietary intervention, no statistically significant difference was found in the number of participants with at least one recurrent adenoma (1 RCT, n = 1905, RR 0.97, 95% CI 0.78 to 1.20), or with more than one adenoma (1 RCT, n = 1905, RR 0.89, 95% CI 0.64 to 1.24). More participants given ispaghula husk group had at least one recurrent adenoma than the control group (1 RCT, n = 376, RR 1.45, 95% CI 1.01 to 2.08). Other analyses by types of fibre intervention were not statistically significant. The overall dropout rate was over 16% in these trials with no reasons given for these losses. Sensitivity analysis incorporating these missing data shows that none of the results can be considered as robust; when the large numbers of participants lost to follow-up were assumed to have had an event or not, the results changed sufficiently to alter the conclusions that we would draw. Therefore, the reliability of the findings may have been compromised by these missing data (attrition bias) and should be interpreted with caution. AUTHORS' CONCLUSIONS There is a lack of evidence from existing RCTs to suggest that increased dietary fibre intake will reduce the recurrence of adenomatous polyps in those with a history of adenomatous polyps within a two to eight year period. However, these results may be unreliable and should be interpreted cautiously, not only because of the high rate of loss to follow-up, but also because adenomatous polyp is a surrogate outcome for the unobserved true endpoint CRC. Longer-term trials with higher dietary fibre levels are needed to enable confident conclusion.
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Affiliation(s)
- Yibo Yao
- Longhua Hospital, Shanghai Traditional Chinese Medicine UniversityDepartment of Anorectal Surgery725 South Wanping Road, Xuhui DistrictShanghaiShanghaiChina200032
| | - Tao Suo
- Zhongshan Hospital, Fudan UniversityDepartment of General Surgery, Institute of General Surgery180 Fenglin Road, Xuhui DistrictShanghaiShanghaiChina200032
| | - Roland Andersson
- Faculty of Medicine, Lund UniversityDepartment of Surgery, Clinical SciencesLund University HospitalLundSwedenSE‐221 85
| | - Yongqing Cao
- Longhua Hospital, Shanghai Traditional Chinese Medicine UniversityDepartment of Anorectal Surgery725 South Wanping Road, Xuhui DistrictShanghaiShanghaiChina200032
| | - Chen Wang
- Longhua Hospital, Shanghai Traditional Chinese Medicine UniversityDepartment of Anorectal Surgery725 South Wanping Road, Xuhui DistrictShanghaiShanghaiChina200032
| | - Jingen Lu
- Longhua Hospital, Shanghai Traditional Chinese Medicine UniversityDepartment of Anorectal Surgery725 South Wanping Road, Xuhui DistrictShanghaiShanghaiChina200032
| | - Evelyne Chui
- Systematic Review Solutions Ltd5‐6 West Tashan RoadYan TaiChina264000
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Mismatch Repair and Colon Cancer: Mechanisms and Therapies Explored. Trends Mol Med 2016; 22:274-289. [PMID: 26970951 DOI: 10.1016/j.molmed.2016.02.003] [Citation(s) in RCA: 131] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2016] [Revised: 02/16/2016] [Accepted: 02/17/2016] [Indexed: 02/06/2023]
Abstract
Colorectal cancer (CRC) remains one of the most prevalent cancers worldwide. In sporadic CRC, mutations frequently occur in the DNA mismatch repair (MMR) pathway. In addition, germline MMR mutations have been linked to Lynch syndrome, the most common form of hereditary CRC. Although genetic mutations, diet, inflammation, and the gut microbiota can influence CRC, it is unclear how MMR deficiency relates to these factors to modulate disease. In this review, the association of MMR to the etiology of CRC is examined, particularly in the context of microRNAs (miRNAs), inflammation, and the microbiome. We also discuss the most current targeted therapies, methods of prevention, and molecular biomarkers against MMR-deficient CRC, all of which are encouraging advancements in the field.
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So EY, Ouchi M, Cuesta-Sancho S, Olson SL, Reif D, Shimomura K, Ouchi T. Tumor suppression by resistant maltodextrin, Fibersol-2. Cancer Biol Ther 2016; 16:460-5. [PMID: 25692338 DOI: 10.1080/15384047.2015.1009269] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
Resistant maltodextrin Fibersol-2 is a soluble and fermentable dietary fiber that is Generally Recognized As Safe (GRAS) in the United States. We tested whether Fibersol-2 contains anti-tumor activity. Human colorectal cancer cell line, HCT116, and its isogenic cells were treated with FIbersol-2. Tumor growth and tumorigenesis were studied in vitro and in vivo. Apoptotic pathway and generation of reactive oxygen species (ROS) were investigated. We discovered that Fibersol-2 significantly inhibits tumor growth of HCT116 cells by inducing apoptosis. Fibersol-2 strongly induces mitochondrial ROS and Bax-dependent cleavage of caspase 3 and 9, which is shown by isogenic HCT116 variants. Fibersol-2 induces phosphorylation of Akt, mTOR in parental HCT116 cells, but not in HCT116 deficient for Bax or p53. It prevents growth of tumor xenograft without any apparent signs of toxicity in vivo. These results identify Fibersol-2 as a mechanism-based dietary supplement agent that could prevent colorectal cancer development.
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Affiliation(s)
- Eui Young So
- a Department of Cancer Genetics ; Roswell Park Cancer Institute ; Buffalo , NY USA
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Movahedi M, Bishop DT, Macrae F, Mecklin JP, Moeslein G, Olschwang S, Eccles D, Evans DG, Maher ER, Bertario L, Bisgaard ML, Dunlop MG, Ho JWC, Hodgson SV, Lindblom A, Lubinski J, Morrison PJ, Murday V, Ramesar RS, Side L, Scott RJ, Thomas HJW, Vasen HF, Burn J, Mathers JC. Obesity, Aspirin, and Risk of Colorectal Cancer in Carriers of Hereditary Colorectal Cancer: A Prospective Investigation in the CAPP2 Study. J Clin Oncol 2015; 33:3591-7. [PMID: 26282643 DOI: 10.1200/jco.2014.58.9952] [Citation(s) in RCA: 88] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
PURPOSE In the general population, increased adiposity is a significant risk factor for colorectal cancer (CRC), but whether obesity has similar effects in those with hereditary CRC is uncertain. This prospective study investigated the association between body mass index and cancer risk in patients with Lynch syndrome (LS). PATIENTS AND METHODS Participants with LS were recruited to the CAPP2 study, in which they were randomly assigned to receive aspirin 600 mg per day or aspirin placebo, plus resistant starch 30 g per day or starch placebo (2 × 2 factorial design). Mean intervention period was 25.0 months, and mean follow-up was 55.7 months. RESULTS During follow-up, 55 of 937 participants developed CRC. For obese participants, CRC risk was 2.41× (95% CI, 1.22 to 4.85) greater than for underweight and normal-weight participants (reference group), and CRC risk increased by 7% for each 1-kg/m(2) increase in body mass index. The risk of all LS-related cancers in obese people was 1.77× (95% CI, 1.06 to 2.96; P = .03) greater than for the reference group. In subgroup analysis, obesity was associated with 3.72× (95% CI, 1.41 to 9.81) greater CRC risk in patients with LS with MLH1 mutation, but no excess risk was observed in those with MSH2 or MSH6 mutation (P = .5). The obesity-related excess CRC risk was confined to those randomly assigned to the aspirin placebo group (adjusted hazard ratio, 2.75; 95% CI, 1.12 to 6.79; P = .03). CONCLUSION Obesity is associated with substantially increased CRC risk in patients with LS, but this risk is abrogated in those taking aspirin. Such patients are likely to benefit from obesity prevention and/or regular aspirin.
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Affiliation(s)
- Mohammad Movahedi
- Mohammad Movahedi, Beheshti University of Medical Sciences, Tehran, Iran; Mohammad Movahedi and D. Timothy Bishop, University of Leeds, Leeds; Diana Eccles, University of Southampton, Southampton; D. Gareth Evans, St Mary's Hospital, Manchester; Eamonn R. Maher, University of Birmingham, Birmingham; Malcolm G. Dunlop, Western General Hospital, Edinburgh; Shirley V. Hodgson, St George's Hospital; Lucy Side, University College London; Huw J.W. Thomas, St Mark's Hospital, Imperial College, London; Patrick J. Morrison, Queens University Belfast, Belfast City Hospital Health and Social Care Trust, Belfast; Victoria Murday, Yorkhill Hospital, Glasgow; John Burn and John C. Mathers, Newcastle University, Newcastle upon Tyne, United Kingdom; Finlay Macrae, Royal Melbourne Hospital, Melbourne, Victoria; Rodney J. Scott, John Hunter Hospital, New Lambton, New South Wales, Australia; Jukka-Pekka Mecklin, Jyväskylä Central Hospital, Jyväskylä, Finland; Gabriela Moeslein, HELIOS St Josefs Hospital, Bochum-Linden, Germany; Sylviane Olschwang, Institut Paoli Calmettes, Marseille, France; Lucio Bertario, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; Marie-Luise Bisgaard, University of Copenhagen, Hvidovre, Denmark; Judy W.C. Ho, Queen Mary Hospital, Hong Kong, Special Administrative Region, People's Republic of China; Annika Lindblom, Karolinska Institutet, Stockholm, Sweden; Jan Lubinski, International Hereditary Cancer Centre, Szczecin, Poland; Raj S. Ramesar, University of Cape Town, South Africa; and Hans F. Vasen, Netherlands Foundation of the Detection of Hereditary Tumours and Leiden University, Leiden, the Netherlands
| | - D Timothy Bishop
- Mohammad Movahedi, Beheshti University of Medical Sciences, Tehran, Iran; Mohammad Movahedi and D. Timothy Bishop, University of Leeds, Leeds; Diana Eccles, University of Southampton, Southampton; D. Gareth Evans, St Mary's Hospital, Manchester; Eamonn R. Maher, University of Birmingham, Birmingham; Malcolm G. Dunlop, Western General Hospital, Edinburgh; Shirley V. Hodgson, St George's Hospital; Lucy Side, University College London; Huw J.W. Thomas, St Mark's Hospital, Imperial College, London; Patrick J. Morrison, Queens University Belfast, Belfast City Hospital Health and Social Care Trust, Belfast; Victoria Murday, Yorkhill Hospital, Glasgow; John Burn and John C. Mathers, Newcastle University, Newcastle upon Tyne, United Kingdom; Finlay Macrae, Royal Melbourne Hospital, Melbourne, Victoria; Rodney J. Scott, John Hunter Hospital, New Lambton, New South Wales, Australia; Jukka-Pekka Mecklin, Jyväskylä Central Hospital, Jyväskylä, Finland; Gabriela Moeslein, HELIOS St Josefs Hospital, Bochum-Linden, Germany; Sylviane Olschwang, Institut Paoli Calmettes, Marseille, France; Lucio Bertario, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; Marie-Luise Bisgaard, University of Copenhagen, Hvidovre, Denmark; Judy W.C. Ho, Queen Mary Hospital, Hong Kong, Special Administrative Region, People's Republic of China; Annika Lindblom, Karolinska Institutet, Stockholm, Sweden; Jan Lubinski, International Hereditary Cancer Centre, Szczecin, Poland; Raj S. Ramesar, University of Cape Town, South Africa; and Hans F. Vasen, Netherlands Foundation of the Detection of Hereditary Tumours and Leiden University, Leiden, the Netherlands
| | - Finlay Macrae
- Mohammad Movahedi, Beheshti University of Medical Sciences, Tehran, Iran; Mohammad Movahedi and D. Timothy Bishop, University of Leeds, Leeds; Diana Eccles, University of Southampton, Southampton; D. Gareth Evans, St Mary's Hospital, Manchester; Eamonn R. Maher, University of Birmingham, Birmingham; Malcolm G. Dunlop, Western General Hospital, Edinburgh; Shirley V. Hodgson, St George's Hospital; Lucy Side, University College London; Huw J.W. Thomas, St Mark's Hospital, Imperial College, London; Patrick J. Morrison, Queens University Belfast, Belfast City Hospital Health and Social Care Trust, Belfast; Victoria Murday, Yorkhill Hospital, Glasgow; John Burn and John C. Mathers, Newcastle University, Newcastle upon Tyne, United Kingdom; Finlay Macrae, Royal Melbourne Hospital, Melbourne, Victoria; Rodney J. Scott, John Hunter Hospital, New Lambton, New South Wales, Australia; Jukka-Pekka Mecklin, Jyväskylä Central Hospital, Jyväskylä, Finland; Gabriela Moeslein, HELIOS St Josefs Hospital, Bochum-Linden, Germany; Sylviane Olschwang, Institut Paoli Calmettes, Marseille, France; Lucio Bertario, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; Marie-Luise Bisgaard, University of Copenhagen, Hvidovre, Denmark; Judy W.C. Ho, Queen Mary Hospital, Hong Kong, Special Administrative Region, People's Republic of China; Annika Lindblom, Karolinska Institutet, Stockholm, Sweden; Jan Lubinski, International Hereditary Cancer Centre, Szczecin, Poland; Raj S. Ramesar, University of Cape Town, South Africa; and Hans F. Vasen, Netherlands Foundation of the Detection of Hereditary Tumours and Leiden University, Leiden, the Netherlands
| | - Jukka-Pekka Mecklin
- Mohammad Movahedi, Beheshti University of Medical Sciences, Tehran, Iran; Mohammad Movahedi and D. Timothy Bishop, University of Leeds, Leeds; Diana Eccles, University of Southampton, Southampton; D. Gareth Evans, St Mary's Hospital, Manchester; Eamonn R. Maher, University of Birmingham, Birmingham; Malcolm G. Dunlop, Western General Hospital, Edinburgh; Shirley V. Hodgson, St George's Hospital; Lucy Side, University College London; Huw J.W. Thomas, St Mark's Hospital, Imperial College, London; Patrick J. Morrison, Queens University Belfast, Belfast City Hospital Health and Social Care Trust, Belfast; Victoria Murday, Yorkhill Hospital, Glasgow; John Burn and John C. Mathers, Newcastle University, Newcastle upon Tyne, United Kingdom; Finlay Macrae, Royal Melbourne Hospital, Melbourne, Victoria; Rodney J. Scott, John Hunter Hospital, New Lambton, New South Wales, Australia; Jukka-Pekka Mecklin, Jyväskylä Central Hospital, Jyväskylä, Finland; Gabriela Moeslein, HELIOS St Josefs Hospital, Bochum-Linden, Germany; Sylviane Olschwang, Institut Paoli Calmettes, Marseille, France; Lucio Bertario, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; Marie-Luise Bisgaard, University of Copenhagen, Hvidovre, Denmark; Judy W.C. Ho, Queen Mary Hospital, Hong Kong, Special Administrative Region, People's Republic of China; Annika Lindblom, Karolinska Institutet, Stockholm, Sweden; Jan Lubinski, International Hereditary Cancer Centre, Szczecin, Poland; Raj S. Ramesar, University of Cape Town, South Africa; and Hans F. Vasen, Netherlands Foundation of the Detection of Hereditary Tumours and Leiden University, Leiden, the Netherlands
| | - Gabriela Moeslein
- Mohammad Movahedi, Beheshti University of Medical Sciences, Tehran, Iran; Mohammad Movahedi and D. Timothy Bishop, University of Leeds, Leeds; Diana Eccles, University of Southampton, Southampton; D. Gareth Evans, St Mary's Hospital, Manchester; Eamonn R. Maher, University of Birmingham, Birmingham; Malcolm G. Dunlop, Western General Hospital, Edinburgh; Shirley V. Hodgson, St George's Hospital; Lucy Side, University College London; Huw J.W. Thomas, St Mark's Hospital, Imperial College, London; Patrick J. Morrison, Queens University Belfast, Belfast City Hospital Health and Social Care Trust, Belfast; Victoria Murday, Yorkhill Hospital, Glasgow; John Burn and John C. Mathers, Newcastle University, Newcastle upon Tyne, United Kingdom; Finlay Macrae, Royal Melbourne Hospital, Melbourne, Victoria; Rodney J. Scott, John Hunter Hospital, New Lambton, New South Wales, Australia; Jukka-Pekka Mecklin, Jyväskylä Central Hospital, Jyväskylä, Finland; Gabriela Moeslein, HELIOS St Josefs Hospital, Bochum-Linden, Germany; Sylviane Olschwang, Institut Paoli Calmettes, Marseille, France; Lucio Bertario, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; Marie-Luise Bisgaard, University of Copenhagen, Hvidovre, Denmark; Judy W.C. Ho, Queen Mary Hospital, Hong Kong, Special Administrative Region, People's Republic of China; Annika Lindblom, Karolinska Institutet, Stockholm, Sweden; Jan Lubinski, International Hereditary Cancer Centre, Szczecin, Poland; Raj S. Ramesar, University of Cape Town, South Africa; and Hans F. Vasen, Netherlands Foundation of the Detection of Hereditary Tumours and Leiden University, Leiden, the Netherlands
| | - Sylviane Olschwang
- Mohammad Movahedi, Beheshti University of Medical Sciences, Tehran, Iran; Mohammad Movahedi and D. Timothy Bishop, University of Leeds, Leeds; Diana Eccles, University of Southampton, Southampton; D. Gareth Evans, St Mary's Hospital, Manchester; Eamonn R. Maher, University of Birmingham, Birmingham; Malcolm G. Dunlop, Western General Hospital, Edinburgh; Shirley V. Hodgson, St George's Hospital; Lucy Side, University College London; Huw J.W. Thomas, St Mark's Hospital, Imperial College, London; Patrick J. Morrison, Queens University Belfast, Belfast City Hospital Health and Social Care Trust, Belfast; Victoria Murday, Yorkhill Hospital, Glasgow; John Burn and John C. Mathers, Newcastle University, Newcastle upon Tyne, United Kingdom; Finlay Macrae, Royal Melbourne Hospital, Melbourne, Victoria; Rodney J. Scott, John Hunter Hospital, New Lambton, New South Wales, Australia; Jukka-Pekka Mecklin, Jyväskylä Central Hospital, Jyväskylä, Finland; Gabriela Moeslein, HELIOS St Josefs Hospital, Bochum-Linden, Germany; Sylviane Olschwang, Institut Paoli Calmettes, Marseille, France; Lucio Bertario, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; Marie-Luise Bisgaard, University of Copenhagen, Hvidovre, Denmark; Judy W.C. Ho, Queen Mary Hospital, Hong Kong, Special Administrative Region, People's Republic of China; Annika Lindblom, Karolinska Institutet, Stockholm, Sweden; Jan Lubinski, International Hereditary Cancer Centre, Szczecin, Poland; Raj S. Ramesar, University of Cape Town, South Africa; and Hans F. Vasen, Netherlands Foundation of the Detection of Hereditary Tumours and Leiden University, Leiden, the Netherlands
| | - Diana Eccles
- Mohammad Movahedi, Beheshti University of Medical Sciences, Tehran, Iran; Mohammad Movahedi and D. Timothy Bishop, University of Leeds, Leeds; Diana Eccles, University of Southampton, Southampton; D. Gareth Evans, St Mary's Hospital, Manchester; Eamonn R. Maher, University of Birmingham, Birmingham; Malcolm G. Dunlop, Western General Hospital, Edinburgh; Shirley V. Hodgson, St George's Hospital; Lucy Side, University College London; Huw J.W. Thomas, St Mark's Hospital, Imperial College, London; Patrick J. Morrison, Queens University Belfast, Belfast City Hospital Health and Social Care Trust, Belfast; Victoria Murday, Yorkhill Hospital, Glasgow; John Burn and John C. Mathers, Newcastle University, Newcastle upon Tyne, United Kingdom; Finlay Macrae, Royal Melbourne Hospital, Melbourne, Victoria; Rodney J. Scott, John Hunter Hospital, New Lambton, New South Wales, Australia; Jukka-Pekka Mecklin, Jyväskylä Central Hospital, Jyväskylä, Finland; Gabriela Moeslein, HELIOS St Josefs Hospital, Bochum-Linden, Germany; Sylviane Olschwang, Institut Paoli Calmettes, Marseille, France; Lucio Bertario, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; Marie-Luise Bisgaard, University of Copenhagen, Hvidovre, Denmark; Judy W.C. Ho, Queen Mary Hospital, Hong Kong, Special Administrative Region, People's Republic of China; Annika Lindblom, Karolinska Institutet, Stockholm, Sweden; Jan Lubinski, International Hereditary Cancer Centre, Szczecin, Poland; Raj S. Ramesar, University of Cape Town, South Africa; and Hans F. Vasen, Netherlands Foundation of the Detection of Hereditary Tumours and Leiden University, Leiden, the Netherlands
| | - D Gareth Evans
- Mohammad Movahedi, Beheshti University of Medical Sciences, Tehran, Iran; Mohammad Movahedi and D. Timothy Bishop, University of Leeds, Leeds; Diana Eccles, University of Southampton, Southampton; D. Gareth Evans, St Mary's Hospital, Manchester; Eamonn R. Maher, University of Birmingham, Birmingham; Malcolm G. Dunlop, Western General Hospital, Edinburgh; Shirley V. Hodgson, St George's Hospital; Lucy Side, University College London; Huw J.W. Thomas, St Mark's Hospital, Imperial College, London; Patrick J. Morrison, Queens University Belfast, Belfast City Hospital Health and Social Care Trust, Belfast; Victoria Murday, Yorkhill Hospital, Glasgow; John Burn and John C. Mathers, Newcastle University, Newcastle upon Tyne, United Kingdom; Finlay Macrae, Royal Melbourne Hospital, Melbourne, Victoria; Rodney J. Scott, John Hunter Hospital, New Lambton, New South Wales, Australia; Jukka-Pekka Mecklin, Jyväskylä Central Hospital, Jyväskylä, Finland; Gabriela Moeslein, HELIOS St Josefs Hospital, Bochum-Linden, Germany; Sylviane Olschwang, Institut Paoli Calmettes, Marseille, France; Lucio Bertario, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; Marie-Luise Bisgaard, University of Copenhagen, Hvidovre, Denmark; Judy W.C. Ho, Queen Mary Hospital, Hong Kong, Special Administrative Region, People's Republic of China; Annika Lindblom, Karolinska Institutet, Stockholm, Sweden; Jan Lubinski, International Hereditary Cancer Centre, Szczecin, Poland; Raj S. Ramesar, University of Cape Town, South Africa; and Hans F. Vasen, Netherlands Foundation of the Detection of Hereditary Tumours and Leiden University, Leiden, the Netherlands
| | - Eamonn R Maher
- Mohammad Movahedi, Beheshti University of Medical Sciences, Tehran, Iran; Mohammad Movahedi and D. Timothy Bishop, University of Leeds, Leeds; Diana Eccles, University of Southampton, Southampton; D. Gareth Evans, St Mary's Hospital, Manchester; Eamonn R. Maher, University of Birmingham, Birmingham; Malcolm G. Dunlop, Western General Hospital, Edinburgh; Shirley V. Hodgson, St George's Hospital; Lucy Side, University College London; Huw J.W. Thomas, St Mark's Hospital, Imperial College, London; Patrick J. Morrison, Queens University Belfast, Belfast City Hospital Health and Social Care Trust, Belfast; Victoria Murday, Yorkhill Hospital, Glasgow; John Burn and John C. Mathers, Newcastle University, Newcastle upon Tyne, United Kingdom; Finlay Macrae, Royal Melbourne Hospital, Melbourne, Victoria; Rodney J. Scott, John Hunter Hospital, New Lambton, New South Wales, Australia; Jukka-Pekka Mecklin, Jyväskylä Central Hospital, Jyväskylä, Finland; Gabriela Moeslein, HELIOS St Josefs Hospital, Bochum-Linden, Germany; Sylviane Olschwang, Institut Paoli Calmettes, Marseille, France; Lucio Bertario, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; Marie-Luise Bisgaard, University of Copenhagen, Hvidovre, Denmark; Judy W.C. Ho, Queen Mary Hospital, Hong Kong, Special Administrative Region, People's Republic of China; Annika Lindblom, Karolinska Institutet, Stockholm, Sweden; Jan Lubinski, International Hereditary Cancer Centre, Szczecin, Poland; Raj S. Ramesar, University of Cape Town, South Africa; and Hans F. Vasen, Netherlands Foundation of the Detection of Hereditary Tumours and Leiden University, Leiden, the Netherlands
| | - Lucio Bertario
- Mohammad Movahedi, Beheshti University of Medical Sciences, Tehran, Iran; Mohammad Movahedi and D. Timothy Bishop, University of Leeds, Leeds; Diana Eccles, University of Southampton, Southampton; D. Gareth Evans, St Mary's Hospital, Manchester; Eamonn R. Maher, University of Birmingham, Birmingham; Malcolm G. Dunlop, Western General Hospital, Edinburgh; Shirley V. Hodgson, St George's Hospital; Lucy Side, University College London; Huw J.W. Thomas, St Mark's Hospital, Imperial College, London; Patrick J. Morrison, Queens University Belfast, Belfast City Hospital Health and Social Care Trust, Belfast; Victoria Murday, Yorkhill Hospital, Glasgow; John Burn and John C. Mathers, Newcastle University, Newcastle upon Tyne, United Kingdom; Finlay Macrae, Royal Melbourne Hospital, Melbourne, Victoria; Rodney J. Scott, John Hunter Hospital, New Lambton, New South Wales, Australia; Jukka-Pekka Mecklin, Jyväskylä Central Hospital, Jyväskylä, Finland; Gabriela Moeslein, HELIOS St Josefs Hospital, Bochum-Linden, Germany; Sylviane Olschwang, Institut Paoli Calmettes, Marseille, France; Lucio Bertario, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; Marie-Luise Bisgaard, University of Copenhagen, Hvidovre, Denmark; Judy W.C. Ho, Queen Mary Hospital, Hong Kong, Special Administrative Region, People's Republic of China; Annika Lindblom, Karolinska Institutet, Stockholm, Sweden; Jan Lubinski, International Hereditary Cancer Centre, Szczecin, Poland; Raj S. Ramesar, University of Cape Town, South Africa; and Hans F. Vasen, Netherlands Foundation of the Detection of Hereditary Tumours and Leiden University, Leiden, the Netherlands
| | - Marie-Luise Bisgaard
- Mohammad Movahedi, Beheshti University of Medical Sciences, Tehran, Iran; Mohammad Movahedi and D. Timothy Bishop, University of Leeds, Leeds; Diana Eccles, University of Southampton, Southampton; D. Gareth Evans, St Mary's Hospital, Manchester; Eamonn R. Maher, University of Birmingham, Birmingham; Malcolm G. Dunlop, Western General Hospital, Edinburgh; Shirley V. Hodgson, St George's Hospital; Lucy Side, University College London; Huw J.W. Thomas, St Mark's Hospital, Imperial College, London; Patrick J. Morrison, Queens University Belfast, Belfast City Hospital Health and Social Care Trust, Belfast; Victoria Murday, Yorkhill Hospital, Glasgow; John Burn and John C. Mathers, Newcastle University, Newcastle upon Tyne, United Kingdom; Finlay Macrae, Royal Melbourne Hospital, Melbourne, Victoria; Rodney J. Scott, John Hunter Hospital, New Lambton, New South Wales, Australia; Jukka-Pekka Mecklin, Jyväskylä Central Hospital, Jyväskylä, Finland; Gabriela Moeslein, HELIOS St Josefs Hospital, Bochum-Linden, Germany; Sylviane Olschwang, Institut Paoli Calmettes, Marseille, France; Lucio Bertario, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; Marie-Luise Bisgaard, University of Copenhagen, Hvidovre, Denmark; Judy W.C. Ho, Queen Mary Hospital, Hong Kong, Special Administrative Region, People's Republic of China; Annika Lindblom, Karolinska Institutet, Stockholm, Sweden; Jan Lubinski, International Hereditary Cancer Centre, Szczecin, Poland; Raj S. Ramesar, University of Cape Town, South Africa; and Hans F. Vasen, Netherlands Foundation of the Detection of Hereditary Tumours and Leiden University, Leiden, the Netherlands
| | - Malcolm G Dunlop
- Mohammad Movahedi, Beheshti University of Medical Sciences, Tehran, Iran; Mohammad Movahedi and D. Timothy Bishop, University of Leeds, Leeds; Diana Eccles, University of Southampton, Southampton; D. Gareth Evans, St Mary's Hospital, Manchester; Eamonn R. Maher, University of Birmingham, Birmingham; Malcolm G. Dunlop, Western General Hospital, Edinburgh; Shirley V. Hodgson, St George's Hospital; Lucy Side, University College London; Huw J.W. Thomas, St Mark's Hospital, Imperial College, London; Patrick J. Morrison, Queens University Belfast, Belfast City Hospital Health and Social Care Trust, Belfast; Victoria Murday, Yorkhill Hospital, Glasgow; John Burn and John C. Mathers, Newcastle University, Newcastle upon Tyne, United Kingdom; Finlay Macrae, Royal Melbourne Hospital, Melbourne, Victoria; Rodney J. Scott, John Hunter Hospital, New Lambton, New South Wales, Australia; Jukka-Pekka Mecklin, Jyväskylä Central Hospital, Jyväskylä, Finland; Gabriela Moeslein, HELIOS St Josefs Hospital, Bochum-Linden, Germany; Sylviane Olschwang, Institut Paoli Calmettes, Marseille, France; Lucio Bertario, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; Marie-Luise Bisgaard, University of Copenhagen, Hvidovre, Denmark; Judy W.C. Ho, Queen Mary Hospital, Hong Kong, Special Administrative Region, People's Republic of China; Annika Lindblom, Karolinska Institutet, Stockholm, Sweden; Jan Lubinski, International Hereditary Cancer Centre, Szczecin, Poland; Raj S. Ramesar, University of Cape Town, South Africa; and Hans F. Vasen, Netherlands Foundation of the Detection of Hereditary Tumours and Leiden University, Leiden, the Netherlands
| | - Judy W C Ho
- Mohammad Movahedi, Beheshti University of Medical Sciences, Tehran, Iran; Mohammad Movahedi and D. Timothy Bishop, University of Leeds, Leeds; Diana Eccles, University of Southampton, Southampton; D. Gareth Evans, St Mary's Hospital, Manchester; Eamonn R. Maher, University of Birmingham, Birmingham; Malcolm G. Dunlop, Western General Hospital, Edinburgh; Shirley V. Hodgson, St George's Hospital; Lucy Side, University College London; Huw J.W. Thomas, St Mark's Hospital, Imperial College, London; Patrick J. Morrison, Queens University Belfast, Belfast City Hospital Health and Social Care Trust, Belfast; Victoria Murday, Yorkhill Hospital, Glasgow; John Burn and John C. Mathers, Newcastle University, Newcastle upon Tyne, United Kingdom; Finlay Macrae, Royal Melbourne Hospital, Melbourne, Victoria; Rodney J. Scott, John Hunter Hospital, New Lambton, New South Wales, Australia; Jukka-Pekka Mecklin, Jyväskylä Central Hospital, Jyväskylä, Finland; Gabriela Moeslein, HELIOS St Josefs Hospital, Bochum-Linden, Germany; Sylviane Olschwang, Institut Paoli Calmettes, Marseille, France; Lucio Bertario, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; Marie-Luise Bisgaard, University of Copenhagen, Hvidovre, Denmark; Judy W.C. Ho, Queen Mary Hospital, Hong Kong, Special Administrative Region, People's Republic of China; Annika Lindblom, Karolinska Institutet, Stockholm, Sweden; Jan Lubinski, International Hereditary Cancer Centre, Szczecin, Poland; Raj S. Ramesar, University of Cape Town, South Africa; and Hans F. Vasen, Netherlands Foundation of the Detection of Hereditary Tumours and Leiden University, Leiden, the Netherlands
| | - Shirley V Hodgson
- Mohammad Movahedi, Beheshti University of Medical Sciences, Tehran, Iran; Mohammad Movahedi and D. Timothy Bishop, University of Leeds, Leeds; Diana Eccles, University of Southampton, Southampton; D. Gareth Evans, St Mary's Hospital, Manchester; Eamonn R. Maher, University of Birmingham, Birmingham; Malcolm G. Dunlop, Western General Hospital, Edinburgh; Shirley V. Hodgson, St George's Hospital; Lucy Side, University College London; Huw J.W. Thomas, St Mark's Hospital, Imperial College, London; Patrick J. Morrison, Queens University Belfast, Belfast City Hospital Health and Social Care Trust, Belfast; Victoria Murday, Yorkhill Hospital, Glasgow; John Burn and John C. Mathers, Newcastle University, Newcastle upon Tyne, United Kingdom; Finlay Macrae, Royal Melbourne Hospital, Melbourne, Victoria; Rodney J. Scott, John Hunter Hospital, New Lambton, New South Wales, Australia; Jukka-Pekka Mecklin, Jyväskylä Central Hospital, Jyväskylä, Finland; Gabriela Moeslein, HELIOS St Josefs Hospital, Bochum-Linden, Germany; Sylviane Olschwang, Institut Paoli Calmettes, Marseille, France; Lucio Bertario, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; Marie-Luise Bisgaard, University of Copenhagen, Hvidovre, Denmark; Judy W.C. Ho, Queen Mary Hospital, Hong Kong, Special Administrative Region, People's Republic of China; Annika Lindblom, Karolinska Institutet, Stockholm, Sweden; Jan Lubinski, International Hereditary Cancer Centre, Szczecin, Poland; Raj S. Ramesar, University of Cape Town, South Africa; and Hans F. Vasen, Netherlands Foundation of the Detection of Hereditary Tumours and Leiden University, Leiden, the Netherlands
| | - Annika Lindblom
- Mohammad Movahedi, Beheshti University of Medical Sciences, Tehran, Iran; Mohammad Movahedi and D. Timothy Bishop, University of Leeds, Leeds; Diana Eccles, University of Southampton, Southampton; D. Gareth Evans, St Mary's Hospital, Manchester; Eamonn R. Maher, University of Birmingham, Birmingham; Malcolm G. Dunlop, Western General Hospital, Edinburgh; Shirley V. Hodgson, St George's Hospital; Lucy Side, University College London; Huw J.W. Thomas, St Mark's Hospital, Imperial College, London; Patrick J. Morrison, Queens University Belfast, Belfast City Hospital Health and Social Care Trust, Belfast; Victoria Murday, Yorkhill Hospital, Glasgow; John Burn and John C. Mathers, Newcastle University, Newcastle upon Tyne, United Kingdom; Finlay Macrae, Royal Melbourne Hospital, Melbourne, Victoria; Rodney J. Scott, John Hunter Hospital, New Lambton, New South Wales, Australia; Jukka-Pekka Mecklin, Jyväskylä Central Hospital, Jyväskylä, Finland; Gabriela Moeslein, HELIOS St Josefs Hospital, Bochum-Linden, Germany; Sylviane Olschwang, Institut Paoli Calmettes, Marseille, France; Lucio Bertario, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; Marie-Luise Bisgaard, University of Copenhagen, Hvidovre, Denmark; Judy W.C. Ho, Queen Mary Hospital, Hong Kong, Special Administrative Region, People's Republic of China; Annika Lindblom, Karolinska Institutet, Stockholm, Sweden; Jan Lubinski, International Hereditary Cancer Centre, Szczecin, Poland; Raj S. Ramesar, University of Cape Town, South Africa; and Hans F. Vasen, Netherlands Foundation of the Detection of Hereditary Tumours and Leiden University, Leiden, the Netherlands
| | - Jan Lubinski
- Mohammad Movahedi, Beheshti University of Medical Sciences, Tehran, Iran; Mohammad Movahedi and D. Timothy Bishop, University of Leeds, Leeds; Diana Eccles, University of Southampton, Southampton; D. Gareth Evans, St Mary's Hospital, Manchester; Eamonn R. Maher, University of Birmingham, Birmingham; Malcolm G. Dunlop, Western General Hospital, Edinburgh; Shirley V. Hodgson, St George's Hospital; Lucy Side, University College London; Huw J.W. Thomas, St Mark's Hospital, Imperial College, London; Patrick J. Morrison, Queens University Belfast, Belfast City Hospital Health and Social Care Trust, Belfast; Victoria Murday, Yorkhill Hospital, Glasgow; John Burn and John C. Mathers, Newcastle University, Newcastle upon Tyne, United Kingdom; Finlay Macrae, Royal Melbourne Hospital, Melbourne, Victoria; Rodney J. Scott, John Hunter Hospital, New Lambton, New South Wales, Australia; Jukka-Pekka Mecklin, Jyväskylä Central Hospital, Jyväskylä, Finland; Gabriela Moeslein, HELIOS St Josefs Hospital, Bochum-Linden, Germany; Sylviane Olschwang, Institut Paoli Calmettes, Marseille, France; Lucio Bertario, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; Marie-Luise Bisgaard, University of Copenhagen, Hvidovre, Denmark; Judy W.C. Ho, Queen Mary Hospital, Hong Kong, Special Administrative Region, People's Republic of China; Annika Lindblom, Karolinska Institutet, Stockholm, Sweden; Jan Lubinski, International Hereditary Cancer Centre, Szczecin, Poland; Raj S. Ramesar, University of Cape Town, South Africa; and Hans F. Vasen, Netherlands Foundation of the Detection of Hereditary Tumours and Leiden University, Leiden, the Netherlands
| | - Patrick J Morrison
- Mohammad Movahedi, Beheshti University of Medical Sciences, Tehran, Iran; Mohammad Movahedi and D. Timothy Bishop, University of Leeds, Leeds; Diana Eccles, University of Southampton, Southampton; D. Gareth Evans, St Mary's Hospital, Manchester; Eamonn R. Maher, University of Birmingham, Birmingham; Malcolm G. Dunlop, Western General Hospital, Edinburgh; Shirley V. Hodgson, St George's Hospital; Lucy Side, University College London; Huw J.W. Thomas, St Mark's Hospital, Imperial College, London; Patrick J. Morrison, Queens University Belfast, Belfast City Hospital Health and Social Care Trust, Belfast; Victoria Murday, Yorkhill Hospital, Glasgow; John Burn and John C. Mathers, Newcastle University, Newcastle upon Tyne, United Kingdom; Finlay Macrae, Royal Melbourne Hospital, Melbourne, Victoria; Rodney J. Scott, John Hunter Hospital, New Lambton, New South Wales, Australia; Jukka-Pekka Mecklin, Jyväskylä Central Hospital, Jyväskylä, Finland; Gabriela Moeslein, HELIOS St Josefs Hospital, Bochum-Linden, Germany; Sylviane Olschwang, Institut Paoli Calmettes, Marseille, France; Lucio Bertario, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; Marie-Luise Bisgaard, University of Copenhagen, Hvidovre, Denmark; Judy W.C. Ho, Queen Mary Hospital, Hong Kong, Special Administrative Region, People's Republic of China; Annika Lindblom, Karolinska Institutet, Stockholm, Sweden; Jan Lubinski, International Hereditary Cancer Centre, Szczecin, Poland; Raj S. Ramesar, University of Cape Town, South Africa; and Hans F. Vasen, Netherlands Foundation of the Detection of Hereditary Tumours and Leiden University, Leiden, the Netherlands
| | - Victoria Murday
- Mohammad Movahedi, Beheshti University of Medical Sciences, Tehran, Iran; Mohammad Movahedi and D. Timothy Bishop, University of Leeds, Leeds; Diana Eccles, University of Southampton, Southampton; D. Gareth Evans, St Mary's Hospital, Manchester; Eamonn R. Maher, University of Birmingham, Birmingham; Malcolm G. Dunlop, Western General Hospital, Edinburgh; Shirley V. Hodgson, St George's Hospital; Lucy Side, University College London; Huw J.W. Thomas, St Mark's Hospital, Imperial College, London; Patrick J. Morrison, Queens University Belfast, Belfast City Hospital Health and Social Care Trust, Belfast; Victoria Murday, Yorkhill Hospital, Glasgow; John Burn and John C. Mathers, Newcastle University, Newcastle upon Tyne, United Kingdom; Finlay Macrae, Royal Melbourne Hospital, Melbourne, Victoria; Rodney J. Scott, John Hunter Hospital, New Lambton, New South Wales, Australia; Jukka-Pekka Mecklin, Jyväskylä Central Hospital, Jyväskylä, Finland; Gabriela Moeslein, HELIOS St Josefs Hospital, Bochum-Linden, Germany; Sylviane Olschwang, Institut Paoli Calmettes, Marseille, France; Lucio Bertario, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; Marie-Luise Bisgaard, University of Copenhagen, Hvidovre, Denmark; Judy W.C. Ho, Queen Mary Hospital, Hong Kong, Special Administrative Region, People's Republic of China; Annika Lindblom, Karolinska Institutet, Stockholm, Sweden; Jan Lubinski, International Hereditary Cancer Centre, Szczecin, Poland; Raj S. Ramesar, University of Cape Town, South Africa; and Hans F. Vasen, Netherlands Foundation of the Detection of Hereditary Tumours and Leiden University, Leiden, the Netherlands
| | - Raj S Ramesar
- Mohammad Movahedi, Beheshti University of Medical Sciences, Tehran, Iran; Mohammad Movahedi and D. Timothy Bishop, University of Leeds, Leeds; Diana Eccles, University of Southampton, Southampton; D. Gareth Evans, St Mary's Hospital, Manchester; Eamonn R. Maher, University of Birmingham, Birmingham; Malcolm G. Dunlop, Western General Hospital, Edinburgh; Shirley V. Hodgson, St George's Hospital; Lucy Side, University College London; Huw J.W. Thomas, St Mark's Hospital, Imperial College, London; Patrick J. Morrison, Queens University Belfast, Belfast City Hospital Health and Social Care Trust, Belfast; Victoria Murday, Yorkhill Hospital, Glasgow; John Burn and John C. Mathers, Newcastle University, Newcastle upon Tyne, United Kingdom; Finlay Macrae, Royal Melbourne Hospital, Melbourne, Victoria; Rodney J. Scott, John Hunter Hospital, New Lambton, New South Wales, Australia; Jukka-Pekka Mecklin, Jyväskylä Central Hospital, Jyväskylä, Finland; Gabriela Moeslein, HELIOS St Josefs Hospital, Bochum-Linden, Germany; Sylviane Olschwang, Institut Paoli Calmettes, Marseille, France; Lucio Bertario, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; Marie-Luise Bisgaard, University of Copenhagen, Hvidovre, Denmark; Judy W.C. Ho, Queen Mary Hospital, Hong Kong, Special Administrative Region, People's Republic of China; Annika Lindblom, Karolinska Institutet, Stockholm, Sweden; Jan Lubinski, International Hereditary Cancer Centre, Szczecin, Poland; Raj S. Ramesar, University of Cape Town, South Africa; and Hans F. Vasen, Netherlands Foundation of the Detection of Hereditary Tumours and Leiden University, Leiden, the Netherlands
| | - Lucy Side
- Mohammad Movahedi, Beheshti University of Medical Sciences, Tehran, Iran; Mohammad Movahedi and D. Timothy Bishop, University of Leeds, Leeds; Diana Eccles, University of Southampton, Southampton; D. Gareth Evans, St Mary's Hospital, Manchester; Eamonn R. Maher, University of Birmingham, Birmingham; Malcolm G. Dunlop, Western General Hospital, Edinburgh; Shirley V. Hodgson, St George's Hospital; Lucy Side, University College London; Huw J.W. Thomas, St Mark's Hospital, Imperial College, London; Patrick J. Morrison, Queens University Belfast, Belfast City Hospital Health and Social Care Trust, Belfast; Victoria Murday, Yorkhill Hospital, Glasgow; John Burn and John C. Mathers, Newcastle University, Newcastle upon Tyne, United Kingdom; Finlay Macrae, Royal Melbourne Hospital, Melbourne, Victoria; Rodney J. Scott, John Hunter Hospital, New Lambton, New South Wales, Australia; Jukka-Pekka Mecklin, Jyväskylä Central Hospital, Jyväskylä, Finland; Gabriela Moeslein, HELIOS St Josefs Hospital, Bochum-Linden, Germany; Sylviane Olschwang, Institut Paoli Calmettes, Marseille, France; Lucio Bertario, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; Marie-Luise Bisgaard, University of Copenhagen, Hvidovre, Denmark; Judy W.C. Ho, Queen Mary Hospital, Hong Kong, Special Administrative Region, People's Republic of China; Annika Lindblom, Karolinska Institutet, Stockholm, Sweden; Jan Lubinski, International Hereditary Cancer Centre, Szczecin, Poland; Raj S. Ramesar, University of Cape Town, South Africa; and Hans F. Vasen, Netherlands Foundation of the Detection of Hereditary Tumours and Leiden University, Leiden, the Netherlands
| | - Rodney J Scott
- Mohammad Movahedi, Beheshti University of Medical Sciences, Tehran, Iran; Mohammad Movahedi and D. Timothy Bishop, University of Leeds, Leeds; Diana Eccles, University of Southampton, Southampton; D. Gareth Evans, St Mary's Hospital, Manchester; Eamonn R. Maher, University of Birmingham, Birmingham; Malcolm G. Dunlop, Western General Hospital, Edinburgh; Shirley V. Hodgson, St George's Hospital; Lucy Side, University College London; Huw J.W. Thomas, St Mark's Hospital, Imperial College, London; Patrick J. Morrison, Queens University Belfast, Belfast City Hospital Health and Social Care Trust, Belfast; Victoria Murday, Yorkhill Hospital, Glasgow; John Burn and John C. Mathers, Newcastle University, Newcastle upon Tyne, United Kingdom; Finlay Macrae, Royal Melbourne Hospital, Melbourne, Victoria; Rodney J. Scott, John Hunter Hospital, New Lambton, New South Wales, Australia; Jukka-Pekka Mecklin, Jyväskylä Central Hospital, Jyväskylä, Finland; Gabriela Moeslein, HELIOS St Josefs Hospital, Bochum-Linden, Germany; Sylviane Olschwang, Institut Paoli Calmettes, Marseille, France; Lucio Bertario, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; Marie-Luise Bisgaard, University of Copenhagen, Hvidovre, Denmark; Judy W.C. Ho, Queen Mary Hospital, Hong Kong, Special Administrative Region, People's Republic of China; Annika Lindblom, Karolinska Institutet, Stockholm, Sweden; Jan Lubinski, International Hereditary Cancer Centre, Szczecin, Poland; Raj S. Ramesar, University of Cape Town, South Africa; and Hans F. Vasen, Netherlands Foundation of the Detection of Hereditary Tumours and Leiden University, Leiden, the Netherlands
| | - Huw J W Thomas
- Mohammad Movahedi, Beheshti University of Medical Sciences, Tehran, Iran; Mohammad Movahedi and D. Timothy Bishop, University of Leeds, Leeds; Diana Eccles, University of Southampton, Southampton; D. Gareth Evans, St Mary's Hospital, Manchester; Eamonn R. Maher, University of Birmingham, Birmingham; Malcolm G. Dunlop, Western General Hospital, Edinburgh; Shirley V. Hodgson, St George's Hospital; Lucy Side, University College London; Huw J.W. Thomas, St Mark's Hospital, Imperial College, London; Patrick J. Morrison, Queens University Belfast, Belfast City Hospital Health and Social Care Trust, Belfast; Victoria Murday, Yorkhill Hospital, Glasgow; John Burn and John C. Mathers, Newcastle University, Newcastle upon Tyne, United Kingdom; Finlay Macrae, Royal Melbourne Hospital, Melbourne, Victoria; Rodney J. Scott, John Hunter Hospital, New Lambton, New South Wales, Australia; Jukka-Pekka Mecklin, Jyväskylä Central Hospital, Jyväskylä, Finland; Gabriela Moeslein, HELIOS St Josefs Hospital, Bochum-Linden, Germany; Sylviane Olschwang, Institut Paoli Calmettes, Marseille, France; Lucio Bertario, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; Marie-Luise Bisgaard, University of Copenhagen, Hvidovre, Denmark; Judy W.C. Ho, Queen Mary Hospital, Hong Kong, Special Administrative Region, People's Republic of China; Annika Lindblom, Karolinska Institutet, Stockholm, Sweden; Jan Lubinski, International Hereditary Cancer Centre, Szczecin, Poland; Raj S. Ramesar, University of Cape Town, South Africa; and Hans F. Vasen, Netherlands Foundation of the Detection of Hereditary Tumours and Leiden University, Leiden, the Netherlands
| | - Hans F Vasen
- Mohammad Movahedi, Beheshti University of Medical Sciences, Tehran, Iran; Mohammad Movahedi and D. Timothy Bishop, University of Leeds, Leeds; Diana Eccles, University of Southampton, Southampton; D. Gareth Evans, St Mary's Hospital, Manchester; Eamonn R. Maher, University of Birmingham, Birmingham; Malcolm G. Dunlop, Western General Hospital, Edinburgh; Shirley V. Hodgson, St George's Hospital; Lucy Side, University College London; Huw J.W. Thomas, St Mark's Hospital, Imperial College, London; Patrick J. Morrison, Queens University Belfast, Belfast City Hospital Health and Social Care Trust, Belfast; Victoria Murday, Yorkhill Hospital, Glasgow; John Burn and John C. Mathers, Newcastle University, Newcastle upon Tyne, United Kingdom; Finlay Macrae, Royal Melbourne Hospital, Melbourne, Victoria; Rodney J. Scott, John Hunter Hospital, New Lambton, New South Wales, Australia; Jukka-Pekka Mecklin, Jyväskylä Central Hospital, Jyväskylä, Finland; Gabriela Moeslein, HELIOS St Josefs Hospital, Bochum-Linden, Germany; Sylviane Olschwang, Institut Paoli Calmettes, Marseille, France; Lucio Bertario, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; Marie-Luise Bisgaard, University of Copenhagen, Hvidovre, Denmark; Judy W.C. Ho, Queen Mary Hospital, Hong Kong, Special Administrative Region, People's Republic of China; Annika Lindblom, Karolinska Institutet, Stockholm, Sweden; Jan Lubinski, International Hereditary Cancer Centre, Szczecin, Poland; Raj S. Ramesar, University of Cape Town, South Africa; and Hans F. Vasen, Netherlands Foundation of the Detection of Hereditary Tumours and Leiden University, Leiden, the Netherlands
| | - John Burn
- Mohammad Movahedi, Beheshti University of Medical Sciences, Tehran, Iran; Mohammad Movahedi and D. Timothy Bishop, University of Leeds, Leeds; Diana Eccles, University of Southampton, Southampton; D. Gareth Evans, St Mary's Hospital, Manchester; Eamonn R. Maher, University of Birmingham, Birmingham; Malcolm G. Dunlop, Western General Hospital, Edinburgh; Shirley V. Hodgson, St George's Hospital; Lucy Side, University College London; Huw J.W. Thomas, St Mark's Hospital, Imperial College, London; Patrick J. Morrison, Queens University Belfast, Belfast City Hospital Health and Social Care Trust, Belfast; Victoria Murday, Yorkhill Hospital, Glasgow; John Burn and John C. Mathers, Newcastle University, Newcastle upon Tyne, United Kingdom; Finlay Macrae, Royal Melbourne Hospital, Melbourne, Victoria; Rodney J. Scott, John Hunter Hospital, New Lambton, New South Wales, Australia; Jukka-Pekka Mecklin, Jyväskylä Central Hospital, Jyväskylä, Finland; Gabriela Moeslein, HELIOS St Josefs Hospital, Bochum-Linden, Germany; Sylviane Olschwang, Institut Paoli Calmettes, Marseille, France; Lucio Bertario, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; Marie-Luise Bisgaard, University of Copenhagen, Hvidovre, Denmark; Judy W.C. Ho, Queen Mary Hospital, Hong Kong, Special Administrative Region, People's Republic of China; Annika Lindblom, Karolinska Institutet, Stockholm, Sweden; Jan Lubinski, International Hereditary Cancer Centre, Szczecin, Poland; Raj S. Ramesar, University of Cape Town, South Africa; and Hans F. Vasen, Netherlands Foundation of the Detection of Hereditary Tumours and Leiden University, Leiden, the Netherlands
| | - John C Mathers
- Mohammad Movahedi, Beheshti University of Medical Sciences, Tehran, Iran; Mohammad Movahedi and D. Timothy Bishop, University of Leeds, Leeds; Diana Eccles, University of Southampton, Southampton; D. Gareth Evans, St Mary's Hospital, Manchester; Eamonn R. Maher, University of Birmingham, Birmingham; Malcolm G. Dunlop, Western General Hospital, Edinburgh; Shirley V. Hodgson, St George's Hospital; Lucy Side, University College London; Huw J.W. Thomas, St Mark's Hospital, Imperial College, London; Patrick J. Morrison, Queens University Belfast, Belfast City Hospital Health and Social Care Trust, Belfast; Victoria Murday, Yorkhill Hospital, Glasgow; John Burn and John C. Mathers, Newcastle University, Newcastle upon Tyne, United Kingdom; Finlay Macrae, Royal Melbourne Hospital, Melbourne, Victoria; Rodney J. Scott, John Hunter Hospital, New Lambton, New South Wales, Australia; Jukka-Pekka Mecklin, Jyväskylä Central Hospital, Jyväskylä, Finland; Gabriela Moeslein, HELIOS St Josefs Hospital, Bochum-Linden, Germany; Sylviane Olschwang, Institut Paoli Calmettes, Marseille, France; Lucio Bertario, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; Marie-Luise Bisgaard, University of Copenhagen, Hvidovre, Denmark; Judy W.C. Ho, Queen Mary Hospital, Hong Kong, Special Administrative Region, People's Republic of China; Annika Lindblom, Karolinska Institutet, Stockholm, Sweden; Jan Lubinski, International Hereditary Cancer Centre, Szczecin, Poland; Raj S. Ramesar, University of Cape Town, South Africa; and Hans F. Vasen, Netherlands Foundation of the Detection of Hereditary Tumours and Leiden University, Leiden, the Netherlands.
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Shou Q, Chen F, Cai Y, Zhang S, Tu J, Zhang L, Wang D, Wang J, Chen M, Fu H. Inhibition of Diethylnitrosamine-Induced Hepatocarcinogenesis in Mice by a High Dietary Protein Intake. Nutr Cancer 2015; 67:1151-8. [PMID: 26359675 DOI: 10.1080/01635581.2015.1073761] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Epidemiological and experimental evidence supports the key role of diet in the development of many types of cancer. Recent studies have suggested that dietary modifications may be beneficial for individuals at high risk for hepatocellular carcinoma (HCC). In this study, we investigated the effect of a high-protein (HP; 20% casein) dietondiethylnitrosamine (DEN)-induced hepatocarcinogenesis. Mice were given free access to water with 30 μg/ml DEN and fed a normal or HP diet for 22 wk. The results showed mice consuming HP diets had reduced mortality rates and body weights and lower hepatic enzyme activity compared to DEN-treated mice on a normal diet. HP consumption also promoted collagen accumulation in the liver, and reduced numbers of proliferating hepatocytes and infiltrating inflammatory cells, as well as decreased expression of inflammatory factor interleukin-1β, and nuclear factor κB activation. These data indicate that HP diets can inhibit DEN-induced hepatocarcinogenesis via suppression of the inflammatory response and provide a new evidence for the dietary management of clinical patients with hepatocellular carcinoma.
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Affiliation(s)
- Qiyang Shou
- a Experimental Animal Research Center, Zhejiang Chinese Medical University , Hangzhou , China
| | - Fangming Chen
- a Experimental Animal Research Center, Zhejiang Chinese Medical University , Hangzhou , China
| | - Yueqin Cai
- a Experimental Animal Research Center, Zhejiang Chinese Medical University , Hangzhou , China
| | - Shanxin Zhang
- b Department of Orthopaedic Surgery , The First Affiliated Hospital of Zhejiang Chinese Medical University , Hangzhou , China
| | - Jue Tu
- a Experimental Animal Research Center, Zhejiang Chinese Medical University , Hangzhou , China
| | - Lizong Zhang
- a Experimental Animal Research Center, Zhejiang Chinese Medical University , Hangzhou , China
| | - Dejun Wang
- a Experimental Animal Research Center, Zhejiang Chinese Medical University , Hangzhou , China
| | - Jianchao Wang
- c Central Laboratory, The Second Clinical Medical College, Zhejiang Chinese Medical University , Hangzhou , China
| | - Minli Chen
- a Experimental Animal Research Center, Zhejiang Chinese Medical University , Hangzhou , China
| | - Huiying Fu
- c Central Laboratory, The Second Clinical Medical College, Zhejiang Chinese Medical University , Hangzhou , China
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Management of Patients with Hereditary Colorectal Cancer Syndromes. GE-PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2015; 22:204-212. [PMID: 28868409 PMCID: PMC5580105 DOI: 10.1016/j.jpge.2015.06.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/17/2015] [Accepted: 06/13/2015] [Indexed: 12/16/2022]
Abstract
Colorectal cancer (CRC) is one of the most important causes of death in the world. Hereditary CRC is found in 5–10% of CRC patients. In this review, we will focus on the major forms of hereditary CRC and their management according to the most recent literature available.
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Butyrylated starch intake can prevent red meat-induced O6-methyl-2-deoxyguanosine adducts in human rectal tissue: a randomised clinical trial. Br J Nutr 2015; 114:220-30. [PMID: 26084032 PMCID: PMC4531472 DOI: 10.1017/s0007114515001750] [Citation(s) in RCA: 109] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Epidemiological studies have identified increased colorectal cancer (CRC) risk with high red meat (HRM) intakes, whereas dietary fibre intake appears to be protective. In the present study, we examined whether a HRM diet increased rectal O(6)-methyl-2-deoxyguanosine (O(6)MeG) adduct levels in healthy human subjects, and whether butyrylated high-amylose maize starch (HAMSB) was protective. A group of twenty-three individuals consumed 300 g/d of cooked red meat without (HRM diet) or with 40 g/d of HAMSB (HRM+HAMSB diet) over 4-week periods separated by a 4-week washout in a randomised cross-over design. Stool and rectal biopsy samples were collected for biochemical, microbial and immunohistochemical analyses at baseline and at the end of each 4-week intervention period. The HRM diet increased rectal O(6)MeG adducts relative to its baseline by 21% (P < 0.01), whereas the addition of HAMSB to the HRM diet prevented this increase. Epithelial proliferation increased with both the HRM (P < 0.001) and HRM + HAMSB (P < 0.05) diets when compared with their respective baseline levels, but was lower following the HRM + HAMSB diet compared with the HRM diet (P < 0.05). Relative to its baseline, the HRM + HAMSB diet increased the excretion of SCFA by over 20% (P < 0.05) and increased the absolute abundances of the Clostridium coccoides group (P < 0.05), the Clostridium leptum group (P < 0.05), Lactobacillus spp. (P < 0.01), Parabacteroides distasonis (P < 0.001) and Ruminococcus bromii (P < 0.05), but lowered Ruminococcus torques (P < 0.05) and the proportions of Ruminococcus gnavus, Ruminococcus torques and Escherichia coli (P < 0.01). HRM consumption could increase the risk of CRC through increased formation of colorectal epithelial O(6)MeG adducts. HAMSB consumption prevented red meat-induced adduct formation, which may be associated with increased stool SCFA levels and/or changes in the microbiota composition.
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Sammour T, Hayes IP, Hill AG, Macrae FA, Winter DC. Familial colorectal cancer syndromes: an overview of clinical management. Expert Rev Gastroenterol Hepatol 2015; 9:757-64. [PMID: 25779305 DOI: 10.1586/17474124.2015.1026328] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Familial colorectal cancer syndromes pose a complex challenge to the treating clinician. Once a syndrome is recognized, genetic testing is often required to confirm the clinical suspicion. Management from that point is usually based on disease-specific guideline recommendations targeting risk reduction for the patient and their relatives through surgery, surveillance and chemoprophylaxis. The aim of this paper is to provide an up-to-date summary of the most common familial syndromes and their medical and surgical management, with specific emphasis on evidence-based interventions that improve patient outcome, and to present the information in a manner that is easily readable and clinically relevant to the treating clinician.
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Affiliation(s)
- Tarik Sammour
- Colorectal Surgery Unit, Department of Surgery, The Royal Melbourne Hospital, Melbourne, VIC, Australia
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50
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Winter JM, Hu Y, Young GP, Kohonen-Corish MRJ, Le Leu RK. Role of Red Meat and Resistant Starch in Promutagenic Adduct Formation, MGMT Repair, Thymic Lymphoma and Intestinal Tumourigenesis in Msh2 -Deficient Mice. JOURNAL OF NUTRIGENETICS AND NUTRIGENOMICS 2015; 7:299-313. [PMID: 26022687 DOI: 10.1159/000381675] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Red meat may increase promutagenic lesions in the colon. Resistant starch (RS) can reduce these lesions and chemically induced colon tumours in rodents. Msh2 is a mismatch repair (MMR) protein, recognising unrepaired promutagenic adducts for removal. We determined if red meat and/or RS modulated DNA adducts or oncogenesis in Msh2-deficient mice. A total of 100 Msh2-/- and 60 wild-type mice consumed 1 of 4 diets for 6 months: control, RS, red meat and red meat+RS. Survival time, aberrant crypt foci (ACF), colon and small intestinal tumours, lymphoma, colonic O6-methyl-2-deoxyguanosine (O6MeG) adducts, methylguanine methyltransferase (MGMT) and cell proliferation were examined. In Msh2-/- mice, red meat enhanced survival compared to control (p<0.01) and lowered total tumour burden compared to RS (p<0.167). Msh2-/- mice had more ACF than wild-type mice (p<0.014), but no colon tumours developed. Msh2-/- increased cell proliferation (p<0.001), lowered DNA O6MeG adducts (p<0.143) and enhanced MGMT protein levels (p<0.001) compared to wild-type mice, with RS supplementation also protecting against DNA adducts (p<0.01). No link between red meat-induced promutagenic adducts and risk for colorectal cancer was observed after 6 months' feeding. Colonic epithelial changes after red meat and RS consumption with MMR deficiency will differ from normal epithelial cells.
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Affiliation(s)
- Jean M Winter
- Flinders Centre for Innovation in Cancer, Flinders University, Bedford Park, S.A., Australia
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