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Kagawa Y. Clinical implications of a machine learning model predicting colorectal polyp recurrence after endoscopic mucosal resection. World J Gastroenterol 2025; 31:107197. [DOI: 10.3748/wjg.v31.i22.107197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2025] [Revised: 04/11/2025] [Accepted: 04/23/2025] [Indexed: 06/12/2025] Open
Abstract
The machine learning model developed by Shi et al for predicting colorectal polyp recurrence after endoscopic mucosal resection represents a significant advancement in the field of clinical gastroenterology. By integrating patient-specific factors, such as age, smoking history, and Helicobacter pylori infection, the eXtreme Gradient Boosting algorithm enables precise personalised colonoscopy follow-up planning and risk assessment. This predictive tool offers substantial benefits by optimising surveillance intervals and directing healthcare resources more efficiently toward high-risk individuals. However, real-world implementation requires consideration of the generalisability of our findings across diverse patient populations and clinician training backgrounds.
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Affiliation(s)
- Yoshinori Kagawa
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka 541-8567, Japan
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Genua F, Butt J, Ganesan H, Waterboer T, Hughes DJ. Association of Antibody Responses to Helicobacter pylori Proteins with Colorectal Adenoma and Colorectal Cancer. Pathogens 2024; 13:897. [PMID: 39452767 PMCID: PMC11510280 DOI: 10.3390/pathogens13100897] [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: 08/22/2024] [Revised: 09/30/2024] [Accepted: 10/08/2024] [Indexed: 10/26/2024] Open
Abstract
Helicobacter pylori (H. pylori) has been implicated in colorectal carcinogenesis. Here, the association of immune responses to bacterial exposure with advancing stages of colorectal neoplasia was assessed by multiplex serology. Immunoglobulin (Ig) A and G antibody responses to thirteen proteins of H. pylori were measured by a Luminex-based multiplex assay in plasma from patients with colorectal cancer (CRC, n = 25), advanced adenoma (n = 82), or small polyps (n = 85) and controls (n = 100). Multivariable logistic regression was used to assess the association of bacterial seropositivity with colorectal neoplasia. The threshold for overall seropositivity required subjects to be positive for at least 4 out of the 13 tested antigens. In a cohort subset with matched data (n = 34), H. pylori seropositivity was correlated with bacterial abundance in both neoplastic and matched normal tissue. While no association was found between H. pylori seropositivity and the presence of CRC, IgA seropositivity to CagA was associated with a decreased risk of advanced adenoma (odds ratio, OR = 0.48, 95% confidence intervals, CIs: 0.24-0.96). Regarding IgG, higher antibody responses to HpaA was associated with advanced adenoma occurrence (OR = 2.46, 95% CI: 1.00-6.01), while responses to HP0395, CagA and Catalase were associated with polyp development (OR = 2.65, 95%, CI: 1.31-5.36, OR = 1.83, 95% CI: 1.01-3.32, and OR = 2.16, CI: 1.09-4.29, respectively). Positive correlations were found between H. pylori abundance in the normal mucosa and levels of both the IgA and IgG antibody response to Catalase and VacA antigens (r = 0.48, p < 0.01; r = 0.37, p = 0.04; r = 0.51, p < 0.01; and r = 0.71, p = 0.04, respectively). Conversely, H. pylori abundance was negatively correlated with levels of IgA antibody response to HpaA and with IgG antibody response to HP0231 in the diseased tissue (r = -0.34, p = 0.04 and r = -0.41, p = 0.01, respectively). The association between levels of H. pylori antigens and colorectal neoplasia risk gradually decreased with the adenoma progression, implicating the early activation of the immune response at the polyp stage. Thus, the evaluation of antibody response to certain bacterial antigens may indicate the presence of early-stage colorectal neoplasia. Further studies are needed to clarify the role H. pylori or the immune response to its antigens may have in colorectal carcinogenesis stages.
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Affiliation(s)
- Flavia Genua
- Molecular Epidemiology of Cancer Group, School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, D04 V1W8 Dublin, Ireland; (F.G.); (H.G.)
- School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, D02 VN51 Dublin, Ireland
| | - Julia Butt
- Infections and Cancer Epidemiology, German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), 69120 Heidelberg, Germany; (J.B.); (T.W.)
| | - Harsha Ganesan
- Molecular Epidemiology of Cancer Group, School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, D04 V1W8 Dublin, Ireland; (F.G.); (H.G.)
| | - Tim Waterboer
- Infections and Cancer Epidemiology, German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), 69120 Heidelberg, Germany; (J.B.); (T.W.)
| | - David J. Hughes
- Molecular Epidemiology of Cancer Group, School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, D04 V1W8 Dublin, Ireland; (F.G.); (H.G.)
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Wang X, Sun T, Fan J, Zuo X, Mao J. Gastrin-related circRNA_0017065 promotes the proliferation and metastasis of colorectal cancer through the miR-3174/RBFOX2 axis. Biol Direct 2024; 19:75. [PMID: 39198845 PMCID: PMC11360539 DOI: 10.1186/s13062-024-00509-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 07/29/2024] [Indexed: 09/01/2024] Open
Abstract
Gastrin is a gastrointestinal peptide hormone that plays an important role in the progression of colorectal cancer (CRC). However, the molecular mechanism remains unclear. In this study, we identified gastrin-related circRNAs via high-throughput sequencing and selected circRNA_0017065 as the research focus. We further studied its specific role and molecular mechanism in the progression of CRC. Knockdown and overexpression of circRNA_0017065 were performed, and the biological function of circRNA_0017065 in CRC progression was studied via in vitro and in vivo functional experiments. The potential downstream target genes were subsequently identified via screening of databases and gene chip data. The expression of circRNA_0017065 in tumour tissues was significantly upregulated compared with that in adjacent normal tissues. In vitro and in vivo functional experiments revealed that the proliferation and migration of CRC cells were significantly suppressed after circRNA_0017065 knockdown, while apoptosis was promoted. After overexpression of circRNA_0017065, the proliferation and migration of CRC cells were significantly promoted, while apoptosis was inhibited. Mechanistic studies revealed that circRNA_0017065 can act as a sponge for miR-3174 and promote CRC progression via the miR-3174/RBFOX2 axis. In general, gastrin-related circRNA_0017065 plays a key role in the occurrence and development of CRC and is expected to be a potential molecular target for the treatment of CRC metastasis.
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Affiliation(s)
- Xu Wang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical College, Wuhu, 241001, China
- Department of Gastrointestinal Surgery, Huzhou Center Hospital, Affiliated Center Hospital HuZhou University, Huzhou, 313000, China
| | - Tianjiao Sun
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical College, Wuhu, 241001, China
| | - Jiapeng Fan
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical College, Wuhu, 241001, China
| | - Xueliang Zuo
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical College, Wuhu, 241001, China.
- Anhui Province Key Laboratory of Non-coding RNA Basic and Clinical Transformation, Wannan Medical College, Wuhu, 241001, China.
| | - Jiading Mao
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical College, Wuhu, 241001, China.
- Anhui Province Key Laboratory of Non-coding RNA Basic and Clinical Transformation, Wannan Medical College, Wuhu, 241001, China.
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Shah SC, Camargo MC, Lamm M, Bustamante R, Roumie CL, Wilson O, Halvorson AE, Greevy R, Liu L, Gupta S, Demb J. Impact of Helicobacter pylori Infection and Treatment on Colorectal Cancer in a Large, Nationwide Cohort. J Clin Oncol 2024; 42:1881-1889. [PMID: 38427927 PMCID: PMC11588569 DOI: 10.1200/jco.23.00703] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 11/04/2023] [Accepted: 12/18/2023] [Indexed: 03/03/2024] Open
Abstract
PURPOSE Helicobacter pylori is the most common cause of infection-associated cancer worldwide. We aimed to evaluate the impact of H. pylori infection and treatment on colorectal cancer (CRC) incidence and mortality. PATIENTS US Veterans who completed H. pylori testing between 1999 and 2018. METHODS We conducted a retrospective cohort analysis among adults within the Veterans Health Administration who completed testing for H. pylori. The primary exposures were (1) H. pylori test result (positive/negative) and (2) H. pylori treatment (untreated/treated) among H. pylori-positive individuals. The primary outcomes were CRC incidence and mortality. Follow-up started at the first H. pylori testing and continued until the earliest of incident or fatal CRC, non-CRC death, or December 31, 2019. RESULTS Among 812,736 individuals tested for H. pylori, 205,178 (25.2%) tested positive. Being H. pylori-positive versus H. pylori-negative was associated with higher CRC incidence and mortality. H. pylori treatment versus no treatment was associated with lower CRC incidence and mortality (absolute risk reduction 0.23%-0.35%) through 15-year follow-up. Being H. pylori-positive versus H. pylori-negative was associated with an 18% (adjusted hazard ratio [adjusted HR], 1.18 [95% CI, 1.12 to 1.24]) and 12% (adjusted HR, 1.12 [95% CI, 1.03 to 1.21]) higher incident and fatal CRC risk, respectively. Individuals with untreated versus treated H. pylori infection had 23% (adjusted HR, 1.23 [95% CI, 1.13 to 1.34]) and 40% (adjusted HR, 1.40 [95% CI, 1.24 to 1.58]) higher incident and fatal CRC risk, respectively. The results were more pronounced in the analysis restricted to individuals with nonserologic testing. CONCLUSION H. pylori positivity may be associated with small but statistically significant higher CRC incidence and mortality; untreated individuals, especially those with confirmed active infection, appear to be most at risk.
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Affiliation(s)
- Shailja C. Shah
- Division of Gastroenterology, VA San Diego Healthcare System, San Diego, CA, USA
- Division of Gastroenterology, University of California, San Diego, San Diego, CA, USA
| | - M. Constanza Camargo
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA
| | - Mark Lamm
- Division of Gastroenterology, VA San Diego Healthcare System, San Diego, CA, USA
| | - Ranier Bustamante
- Division of Gastroenterology, VA San Diego Healthcare System, San Diego, CA, USA
- Division of Gastroenterology, University of California, San Diego, San Diego, CA, USA
| | - Christianne L. Roumie
- Department of Medicine, VA Tennessee Valley Healthcare System, Clinical Services Research and Development, Nashville, TN, USA
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- Department of Medicine, VA Geriatrics Research Education and Clinical Center (GRECC), VA Tennessee Valley Health System, Nashville, TN, USA
| | - Otis Wilson
- Department of Medicine, VA Tennessee Valley Healthcare System, Clinical Services Research and Development, Nashville, TN, USA
| | - Alese E. Halvorson
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Robert Greevy
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Lin Liu
- Division of Biostatistics and Bioinformatics, Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, San Diego, CA, USA
| | - Samir Gupta
- Division of Gastroenterology, VA San Diego Healthcare System, San Diego, CA, USA
- Division of Gastroenterology, University of California, San Diego, San Diego, CA, USA
| | - Joshua Demb
- Division of Gastroenterology, University of California, San Diego, San Diego, CA, USA
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Liu Y, Yang DQ, Jiang JN, Jiao Y. Relationship between Helicobacter pylori infection and colorectal polyp/colorectal cancer. World J Gastrointest Surg 2024; 16:1008-1016. [PMID: 38690050 PMCID: PMC11056658 DOI: 10.4240/wjgs.v16.i4.1008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Revised: 02/01/2024] [Accepted: 03/13/2024] [Indexed: 04/22/2024] Open
Abstract
Helicobacter pylori (H. pylori) plays an important role in the development of gastric cancer, although its association to colorectal polyp (CP) or colorectal cancer (CRC) is unknown. In this issue of World Journal of Gastrointestinal Surgery, Zhang et al investigated the risk factors for H. pylori infection after colon polyp resection. Importantly, the researchers used R software to create a prediction model for H. pylori infection based on their findings. This editorial gives an overview of the association between H. pylori and CP/CRC, including the clinical significance of H. pylori as an independent risk factor for CP/CRC, the underlying processes of H. pylori-associated carcinogenesis, and the possible risk factors and identification of H. pylori.
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Affiliation(s)
- Ying Liu
- Department of General Surgery, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun 130021, Jilin Province, China
| | - Ding-Quan Yang
- Department of Gastrointestinal and Colorectal Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China
| | - Jun-Nan Jiang
- Department of Gastrointestinal and Colorectal Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China
| | - Yan Jiao
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
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Basmaci N, Karataş A, Ergin M, Dumlu GŞ. Association between Helicobacter pylori infection and colorectal polyps. Medicine (Baltimore) 2023; 102:e35591. [PMID: 37861565 PMCID: PMC10589529 DOI: 10.1097/md.0000000000035591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Accepted: 09/20/2023] [Indexed: 10/21/2023] Open
Abstract
It was aimed to investigate whether the Helicobacter pylori infection is related to the frequency, localization, size and number of colorectal polyps. The data of 4561 patients who underwent esophagogastroduodenoscopy and colonoscopy were analyzed retrospectively. Patients with and without polyps at colonoscopy were grouped and the frequency of H pylori infection was compared in these patients. The relationship between the groups was evaluated with statistical methods. It was determined that the rate of H pylori infection was higher in patients with colorectal polyps than in patients without polyps (P < .005). Patients with multiple polyps, polyps larger than 1 cm, and tubulovillous and villous adenoma from polyp types had a higher rate of H pylori infection (P = .095; P .004; P .001). When the polyps were evaluated according to their localization, H pylori infection rates were not different between the groups (P = .341). It has been observed that the rate of H pylori infection is higher in large polyps, multiple polyps, tubulovillous and villous adenomas, which are known to have a higher risk of malignancy.
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Affiliation(s)
- Nergis Basmaci
- Afyonkarahisar Dinar State Hospital, Department of Internal Medicine, Afyonkarahisar, Turkey
| | - Ali Karataş
- Gazi University Faculty of Medicine, Department of Gastroenterology, Ankara, Turkey
| | - Mustafa Ergin
- Aksaray Training and Research Hospital, Department of Gastroenterology, Aksaray, Turkey
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Mendes I, Vale N. How Can the Microbiome Induce Carcinogenesis and Modulate Drug Resistance in Cancer Therapy? Int J Mol Sci 2023; 24:11855. [PMID: 37511612 PMCID: PMC10380870 DOI: 10.3390/ijms241411855] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Revised: 07/18/2023] [Accepted: 07/21/2023] [Indexed: 07/30/2023] Open
Abstract
Over the years, cancer has been affecting the lives of many people globally and it has become one of the most studied diseases. Despite the efforts to understand the cell mechanisms behind this complex disease, not every patient seems to respond to targeted therapies or immunotherapies. Drug resistance in cancer is one of the limiting factors contributing to unsuccessful therapies; therefore, understanding how cancer cells acquire this resistance is essential to help cure individuals affected by cancer. Recently, the altered microbiome was observed to be an important hallmark of cancer and therefore it represents a promising topic of cancer research. Our review aims to provide a global perspective of some cancer hallmarks, for instance how genetic and epigenetic modifications may be caused by an altered human microbiome. We also provide information on how an altered human microbiome can lead to cancer development as well as how the microbiome can influence drug resistance and ultimately targeted therapies. This may be useful to develop alternatives for cancer treatment, i.e., future personalized medicine that can help in cases where traditional cancer treatment is unsuccessful.
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Affiliation(s)
- Inês Mendes
- OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal;
- CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal
- School of Life and Environmental Sciences, University of Trás-os-Montes and Alto Douro (UTAD), Edifício de Geociências, 5000-801 Vila Real, Portugal
| | - Nuno Vale
- OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal;
- CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal
- Department of Community Medicine, Information and Health Decision Sciences (MEDCIDS), Faculty of Medicine, University of Porto, Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal
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Guo CG, Zhang F, Jiang F, Wang L, Chen Y, Zhang W, Zhou A, Zhang S, Leung WK. Long-term effect of Helicobacter pylori eradication on colorectal cancer incidences. Therap Adv Gastroenterol 2023; 16:17562848231170943. [PMID: 37168403 PMCID: PMC10164860 DOI: 10.1177/17562848231170943] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 04/04/2023] [Indexed: 05/13/2023] Open
Abstract
Background There is evidence supporting the association between Helicobacter pylori infection and colorectal cancer (CRC), but whether H. pylori eradication reduces the risk of CRC is still unknown. Objectives To compare the incidence of CRC in subjects who had received H. pylori eradication therapy with general population. Design A population-based retrospective cohort study. Methods This study included all H. pylori-infected subjects who had received their first course of clarithromycin-containing triple therapy in 2003-2015 in Hong Kong. We compared the observed incidences of CRC in this H. pylori eradicated cohort with the expected incidences in the age- and sex-matched general population. The standardized incidence ratio (SIR) with 95% confidence interval (CI) was computed. Results Among 96,572 H. pylori-eradicated subjects with a median follow-up of 9.7 years, 1417 (1.5%) developed CRC. Primary analysis showed no significant difference in the observed and expected incidences of CRC (SIR: 1.03, 95% CI: 0.97-1.09). However, when stratified according to the follow-up period, higher incidence of CRC was only observed in the first 5 years after eradication (SIR: 1.47, 95% CI: 1.39-1.55), but it was lower (SIR: 0.85, 95% CI: 0.74-0.99) than general population after 11 years. When stratified by tumor location, the observed incidence was higher for colon (SIR: 1.20, 95% CI: 1.12-1.29) but lower for rectal cancer (SIR: 0.90, 95% CI: 0.81-0.999) among H. pylori-eradicated subjects. Conclusions H. pylori-infected subjects appeared to have a higher incidence of CRC initially, which declined progressively to a level lower than general population 10 years after H. pylori eradication, particularly for rectal cancer.
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Affiliation(s)
- Chuan-Guo Guo
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
| | - Feifei Zhang
- National Institute of Health Data Science at Peking University, Beijing, China
| | - Fang Jiang
- Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
| | - Lingling Wang
- Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Yijun Chen
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Wenxue Zhang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Anni Zhou
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Shutian Zhang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Wai K. Leung
- Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong 999077, China
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Masood M, Nasser MI. Gut microbial metabolites and colorectal cancer. MICROBIAL BIOMOLECULES 2023:353-373. [DOI: 10.1016/b978-0-323-99476-7.00011-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Wernly S, Semmler G, Flamm M, Rezar R, Aigner E, Datz C, Wernly B. The Association between Helicobacter pylori and Colorectal Neoplasia. Med Princ Pract 2022; 32:77-85. [PMID: 36580903 PMCID: PMC10267487 DOI: 10.1159/000528794] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 12/11/2022] [Indexed: 12/30/2022] Open
Abstract
OBJECTIVES Helicobacter pylori (H. pylori) and colorectal neoplasia (CRN) are frequent entities. Epidemiological data suggest an association between H. pylori positivity (H. pylori +) and CRN, whereas pathophysiologic considerations substantiate a possible causal relationship. However, the relationship between CRN and H. pylori + may also be mediated by shared risk factors. Therefore, the aim of this cross-sectional study was to evaluate a possible independent relationship between H. pylori and CRN in a Central European cohort. METHODS We included 5,707 asymptomatic patients. All patients underwent screening colonoscopy and upper gastrointestinal endoscopy. We assessed the association between any CRN and advanced CRN with H. pylori + using multilevel logistic regression. We adjusted for age, sex, a positive family history of colorectal cancer, and cardiovascular risk. RESULTS 1,082 patients (19%) were H. pylori + and 4,625 (81%) H. pylori -. Patients with both CRN and H. pylori had more cardiometabolic risk factors. In univariate (aOR 1.20; 1.10-1.31) and multivariable analysis (aOR 1.20; 1.08-1.32), H. pylori + was associated with the diagnosis of any CRN. However, H. pylori + was associated with the presence of advanced CRN (aOR 1.26; 0.96-1.64) only in trend. CONCLUSIONS We found a clustered co-occurrence of CRN and H. pylori. This association persisted after correction for shared cardiometabolic risk factors. We suggest that our analysis emphasizes the clinical value of H. pylori eradication. Whether "test and treat" H. pylori is warranted to prevent CRN remains unclear but is at least a possibility given the simplicity of "test and treat."
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Affiliation(s)
- Sarah Wernly
- Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University of Salzburg, Salzburg, Austria
| | - Georg Semmler
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Maria Flamm
- Institute of General Practice, Family Medicine and Preventive Medicine, Paracelsus Medical University of Salzburg, Salzburg, Austria
| | - Richard Rezar
- Department of Cardiology and Intensive Care Medicine, Clinic of Internal Medicine II, University Hospital Salzburg, Paracelsus Medical University of Salzburg, Salzburg, Austria
| | - Elmar Aigner
- Department of Gastroenterology, Hepatology, Nephrology and Diabetology, Clinic of Internal Medicine I, University Hospital Salzburg, Paracelsus Medical University of Salzburg, Salzburg, Austria
| | - Christian Datz
- Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University of Salzburg, Salzburg, Austria
| | - Bernhard Wernly
- Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University of Salzburg, Salzburg, Austria
- Institute of General Practice, Family Medicine and Preventive Medicine, Paracelsus Medical University of Salzburg, Salzburg, Austria
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Haque S, Raina R, Afroze N, Hussain A, Alsulimani A, Singh V, Mishra BN, Kaul S, Kharwar RN. Microbial dysbiosis and epigenetics modulation in cancer development - A chemopreventive approach. Semin Cancer Biol 2022; 86:666-681. [PMID: 34216789 DOI: 10.1016/j.semcancer.2021.06.024] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 06/22/2021] [Accepted: 06/25/2021] [Indexed: 01/27/2023]
Abstract
An overwhelming number of research articles have reported a strong relationship of the microbiome with cancer. Microbes have been observed more commonly in the body fluids like urine, stool, mucus of people with cancer compared to the healthy controls. The microbiota is responsible for both progression and suppression activities of various diseases. Thus, to maintain healthy human physiology, host and microbiota relationship should be in a balanced state. Any disturbance in this equilibrium, referred as microbiome dysbiosis becomes a prime cause for the human body to become more prone to immunodeficiency and cancer. It is well established that some of these microbes are the causative agents, whereas others may encourage the formation of tumours, but very little is known about how these microbial communications causing change at gene and epigenome level and trigger as well as encourage the tumour growth. Various studies have reported that microbes in the gut influence DNA methylation, DNA repair and DNA damage. The genes and pathways that are altered by gut microbes are also associated with cancer advancement, predominantly those implicated in cell growth and cell signalling pathways. This study exhaustively reviews the current research advancements in understanding of dysbiosis linked with colon, lung, ovarian, breast cancers and insights into the potential molecular targets of the microbiome promoting carcinogenesis, the epigenetic alterations of various potential targets by altered microbiota, as well as the role of various chemopreventive agents for timely prevention and customized treatment against various types of cancers.
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Affiliation(s)
- Shafiul Haque
- Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan, 45142, Saudi Arabia; Bursa Uludağ University Faculty of Medicine, Görükle Campus, 16059, Nilüfer, Bursa, Turkey
| | - Ritu Raina
- School of Life Sciences, Manipal Academy of Higher Education, Dubai, United Arab Emirates
| | - Nazia Afroze
- School of Life Sciences, Manipal Academy of Higher Education, Dubai, United Arab Emirates
| | - Arif Hussain
- School of Life Sciences, Manipal Academy of Higher Education, Dubai, United Arab Emirates.
| | - Ahmad Alsulimani
- Medical Laboratory Technology Department, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
| | - Vineeta Singh
- Department of Biotechnology, Institute of Engineering and Technology, Dr. A.P.J. Abdul Kalam Technical University, Lucknow, 226021, Uttar Pradesh, India
| | - Bhartendu Nath Mishra
- Department of Biotechnology, Institute of Engineering and Technology, Dr. A.P.J. Abdul Kalam Technical University, Lucknow, 226021, Uttar Pradesh, India
| | - Sanjana Kaul
- School of Biotechnology, University of Jammu, Jammu, 180006, J&K, India
| | - Ravindra Nath Kharwar
- Centre of Advanced Study in Botany, Banaras Hindu University, Varanasi, 221005, India
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The role of infections in the causation of cancer in Kenya. Cancer Causes Control 2022; 33:1391-1400. [PMID: 36087193 DOI: 10.1007/s10552-022-01625-3] [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: 03/01/2022] [Accepted: 08/31/2022] [Indexed: 12/09/2022]
Abstract
Cancer constitutes a major health care burden in the world today with the situation worsening in resource poor settings as seen in most Sub-Saharan African (SSA) countries. Infections constitute by far the most common risk factors for cancer in SSA and being a typical country in this region, Kenya has experienced an upsurge in the incidence of various types of cancers in the last few decades. Although there is limited population-based data in Kenya of infections-associated cancers, this review provides an up-to-date literature-based discussion on infections-associated cancers, their pathogenesis, and preventive approaches in the country. The primary infectious agents identified are largely viral (human immunodeficiency virus, human papillomavirus (HPV), Kaposi's sarcoma-associated herpes virus, Epstein-Barr virus, hepatitis B virus (HBV), hepatitis C virus), and also bacterial: Helicobacter pylori and parasitic: Schistosomiasis haematobium. Cancers associated with infections in Kenya are varied but the predominant ones are Non-Hodgkin lymphoma, Kaposi's sarcoma, Hodgkin lymphoma, Burkitt's lymphoma, cervical, liver, and gastric cancers. The mechanisms of infections-induced carcinogenesis are varied but they mainly seem to stem from disruption of signaling, chronic inflammation, and immunosuppression. Based on our findings, actionable cancer-preventive measures that are economically feasible and aligned with existing infrastructure in Kenya include screening and treatment of infections, implementation of cancer awareness and screening, and vaccination against infections primarily HBV and HPV. The development of vaccines against other infectious agents associated with causation of cancer remains also as an important goal in cancer prevention.
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YALINBAŞ KAYA B, TUĞRUL F. The relationship between colorectal cancer and gastric histopathology: case-control study. JOURNAL OF HEALTH SCIENCES AND MEDICINE 2022. [DOI: 10.32322/jhsm.1118677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Aim: The aim of this study was to investigate the gastric histopathological findings (Helicobacter pylori (H. pylori), intestinal metaplasia (IM), atrophic gastritis (AG), and dysplasia) in the patients with and without colorectal cancer (CRC).
Material and Method: Two hundred ninety five patients (160 CRC patients and 135 control individuals) were included in the study. Gastric histopathological findings of the patients who underwent upper gastrointestinal (GI) endoscopy were analyzed retrospectively.
Results: H. pylori positivity and IM rates in the CRC patient group were significantly higher than the control group (58.8%&27.8% and 33.1%&19.5%, p<0.001 and p<0.012, respectively). In addition, AG, lymphoplasmocytic infiltration, and dysplasia rates were also higher in the CRC patients compared to the control group. But, they were not statistically significant (p=0.462, p=0.103, and p=0.195, respectively).
Conclusion: In our study, the frequency of H. pylori and IM in patients with CRC was higher than in the control group. Since the prevalence of H. pylori infection is high in Turkey and H. pylori-related gastric diseases may be potential risk factors for colorectal neoplasia, it is recommended that individuals in the high-risk group to be screened for colonoscopy. Also, upper GI endoscopic examination should be performed to screen for gastric premaling lesions in patients with CRC.
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Affiliation(s)
- Berrin YALINBAŞ KAYA
- SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, ESKİŞEHİR ŞEHİR SAĞLIK UYGULAMA VE ARAŞTIRMA MERKEZİ, DAHİLİ TIP BİLİMLERİ BÖLÜMÜ
| | - Fuzuli TUĞRUL
- SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, ESKİŞEHİR ŞEHİR SAĞLIK UYGULAMA VE ARAŞTIRMA MERKEZİ, DAHİLİ TIP BİLİMLERİ BÖLÜMÜ, RADYASYON ONKOLOJİSİ ANABİLİM DALI
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14
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Zhuang Z, Yu B, Xie M, Zhang Y, Lv B. Association of Helicobacter pylori enrichment in colorectal adenoma tissue on clinical and pathological features of adenoma. Clin Res Hepatol Gastroenterol 2022; 46:101961. [PMID: 35636682 DOI: 10.1016/j.clinre.2022.101961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 05/04/2022] [Accepted: 05/16/2022] [Indexed: 02/04/2023]
Abstract
OBJECTIVE To investigate the enrichment of Helicobacter pylori (Hp) in adenoma tissue of patients with colorectal adenoma, and analyze the correlation between the enrichment and the clinical and pathological characteristics of colorectal adenoma. METHODS The data of 1,622 patients undergoing gastrointestinal endoscopy in the Endoscopy Center of Wenzhou Integrated Traditional Chinese and Western Medicine Hospital affiliated to Zhejiang University of Traditional Chinese Medicine from January 2019 to June 2021 were retrospectively collected. The general data, gastric Hp infection, clinical and pathological features of colorectal adenoma, methylene blue staining of adenoma Hp, immunohistochemistry of adenoma Hp and immunofluorescence staining of adenoma TLR5 protein. were compared between the colorectal adenoma group (743 cases) and the control group (879 cases). RESULTS There were 361 gastric Hp positive cases in the colorectal adenoma group, with a positive rate of 48.59%, and 331 gastric Hp positive cases in the control group, with a positive rate of 37.66%, and the difference was statistically significant (P < 0.001). Gastric Hp infection significantly correlates with the Hp enrichment in colorectal adenomas (OR: 28.449; 95%CI: 18.188-44.500; P < 0.001). Moreover, we found that Hp enrichment in colorectal adenomas was correlated with the diameter, pathological type, and malignancy of adenoma (OR: 3.536; 3.652; 2.833; all P < 0.001). Expression TLR5 protein was also increased in Hp-enriched adenoma tissue. CONCLUSION There is a correlation between gastric Hp infection and intestinal Hp enrichment. The intestinal Hp enrichment significantly correlates with the clinical and pathological characteristics of colorectal adenomas, and its tumor-promoting effect may be related to the up-regulation of mucosal TLR5 expression.
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Affiliation(s)
- Zhaomeng Zhuang
- Zhejiang Chinese Medical University Affiliated Wenzhou Hospital of Integrated, Traditional Chinese and Western Medicine China; Zhejiang Chinese Medical University China.
| | - Bingqu Yu
- Zhejiang Chinese Medical University Affiliated Wenzhou Hospital of Integrated, Traditional Chinese and Western Medicine China
| | - Min Xie
- Zhejiang Chinese Medical University Affiliated Wenzhou Hospital of Integrated, Traditional Chinese and Western Medicine China
| | - Yiguang Zhang
- Zhejiang Chinese Medical University Affiliated Wenzhou Hospital of Integrated, Traditional Chinese and Western Medicine China
| | - Bin Lv
- Zhejiang Chinese Medical University China
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15
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Are Inflammatory Bowel Disease and Colorectal Carcinoma Associated with Helicobacter pylori? A Prospective Study and Meta-analysis. JOURNAL OF PURE AND APPLIED MICROBIOLOGY 2022. [DOI: 10.22207/jpam.16.1.75] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Observational studies regarding the correlation between colorectal carcinoma, inflammatory bowel disease and Helicobacter pylori infection are inconsistent. The present study aims to investigate the association between colorectal adenocarcinoma (CRA) and inflammatory bowel disease (IBD) with H. pylori status in 100 patients who have inflammatory bowel disease and colorectal carcinoma was confirmed disease by histological approach. Besides, a meta-analysis was performed of published studies, to evaluate the link between H. pylori infection and an increased risk of CRC and IBD. Among 67 cases with CRA and 33 cases with IBD, 59.7% and 51.5% were H. pylori positive; respectively. In the meta-analysis, thirty-nine articles were included, involving 13 231 cases with CRC and 2477 with IBD. The pooled odds ratio for CRC and IBD was 1.16 (95%CI = 0.73-1.82) and 0.42 (95%CI = 0.32-0.56); respectively. Our meta-analysis indicates that H. pylori is not associated with CRC.
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16
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Lu D, Wang M, Ke X, Wang Q, Wang J, Li D, Wang M, Wang Q. Association Between H. pylori Infection and Colorectal Polyps: A Meta-Analysis of Observational Studies. Front Med (Lausanne) 2022; 8:706036. [PMID: 35118081 PMCID: PMC8803908 DOI: 10.3389/fmed.2021.706036] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 12/20/2021] [Indexed: 11/18/2022] Open
Abstract
Background It has been suggested that Helicobacter pylori (H. pylori) infection is associated with hypergastrinemia and proliferation of colorectal mucosa via direct stimulation, dysbiosis of the gut microbiome, and changes in the gut microbiome, all of which may lead to the formation of colorectal polyps. However, the consensus remains lacking regarding whether H. pylori infection is independently associated with colorectal polyps and whether the association differs according to histological type of colorectal polyps. To summarize the current evidence regarding the relationship between H. pylori infection and colorectal polyps, we conducted a meta-analysis of related observational studies according to the histological types of colorectal polyps. Methods Observational studies investigating the association between H. pylori infection and colorectal polyps using multivariate analyses were included by search of PubMed, Embase, and Web of Science. A random-effects model was adopted to combine the results. Results Seventeen studies that include 322,395 participants were analyzed. It was shown that H. pylori infection was independently associated with overall colorectal polyps (odds ratio [OR]: 1.67, 95% CI: 1.24–2.24, p < 0.001; I2 = 73%). According to the histological type of colorectal polyps, H. pylori infection was independently associated with adenomatous polyps (APs; OR: 1.71, 95% CI: 1.47–1.99, p < 0.001; I2 = 86%), advanced APs (OR: 2.06, 95% CI: 1.56–2.73, p < 0.001; I2 = 0%), and hyperplastic polyps (HPs; OR: 1.54, 95% CI: 1.02–2.30, p = 0.04; I2 = 78%). Evidence based on only one study showed that H. pylori infection was not associated with sessile serrated polyps (SSPs; OR: 1.00, 95% CI: 0.93–1.07, p = 0.99). Conclusions Current evidence from case-control and cross-sectional studies suggested that H. pylori infection was independently associated with colorectal APs, advanced APs, and HPs, but not with SSPs. These findings suggested H. pylori infection may be a possible risk factor of colorectal polyp, which is important for the prevention of colorectal polyp in the adult population.
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Affiliation(s)
- Depeng Lu
- Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Mingyu Wang
- Department of Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Xiquan Ke
- Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Qiangwu Wang
- Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Jianchao Wang
- Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Dapeng Li
- Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Meng Wang
- Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Qizhi Wang
- Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
- *Correspondence: Qizhi Wang
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17
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Manzoor S, Wani SM, Mir SA, Rizwan D. Role of probiotics and prebiotics in mitigation of different diseases. Nutrition 2022; 96:111602. [PMID: 35182833 DOI: 10.1016/j.nut.2022.111602] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Revised: 11/30/2021] [Accepted: 01/13/2022] [Indexed: 11/15/2022]
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18
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Permuth JB, Rahman S, Chen DT, Waterboer T, Giuliano AR. A Case Control Study of the Seroprevalence of Helicobacter pylori Proteins and Their Association with Pancreatic Cancer Risk. J Pancreat Cancer 2021; 7:57-64. [PMID: 34901696 PMCID: PMC8655807 DOI: 10.1089/pancan.2021.0010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/23/2021] [Indexed: 12/12/2022] Open
Abstract
Background: The association between Helicobacter pylori (H. pylori) infection and pancreatic cancer (PC) risk remains inconclusive. We examined the association between H. pylori antibodies and PC risk in a case-control study at a comprehensive cancer center. Methods: Multiplex serology using a glutathione S-transferase capture immunosorbent assay in conjunction with fluorescent bead technology was used to measure antibodies to 15 H. pylori proteins in serum or plasma from 131 incident cases with PC or a PC precursor and 131 healthy controls. Reactivity to ≥4 H. pylori proteins was defined as the overall seroprevalence. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), with adjustment for age at diagnosis/interview, gender, and race. Results: The majority of the sample was 50 years or older, and from the white race group. Half of the sample were women. Seroprevalence ≥4 of H. pylori proteins was 11.1%. Overall, H. pylori seroprevalence was not associated with PC risk (OR: 0.59; 95% CI: 0.25–1.40). The prevalence of several H. pylori-specific proteins HP537 (OR: 1.78; 95% CI: 0.30–10.51), HP305 (OR: 1.38; 95% CI: 0.61–3.16), and HP410 (OR: 1.31; 95% CI: 0.44–3.96) increased the odds of PC. Similarly, H. pylori-specific proteins HP522 (OR: 0.25; 95% CI: 0.04–1.66), HyuA (OR: 0.49; 95% CI: 0.21–1.14), and HP1564 (OR: 0.63; 95% CI: 0.27–1.51) decreased the odds of PC. However, these findings were not statistically significant at α = 0.05. Conclusions: Our findings do not support an association between H. pylori and PC risk. Further evaluation of this lack of association is recommended.
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Affiliation(s)
- Jennifer B Permuth
- Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Shams Rahman
- Department of Public Health and Health Equity, College of Nursing and Health Sciences, Bethune-Cookman University, Daytona, Florida, USA
| | - Dung-Tsa Chen
- Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Tim Waterboer
- Division of Infections and Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany
| | - Anna R Giuliano
- Center of Infection Research in Cancer, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
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19
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Ren JF, Feng P, Zhang QS, Jing DD. Correlation between Helicobacter pylori infection and recurrence of colorectal adenoma. Shijie Huaren Xiaohua Zazhi 2021; 29:952-959. [DOI: 10.11569/wcjd.v29.i16.952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Affiliation(s)
- Jian-Feng Ren
- Department of Gastroenterology, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, China
| | - Ping Feng
- Department of Gastroenterology, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, China
| | - Qi-Sheng Zhang
- Department of Gastroenterology, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, China
| | - Da-Dao Jing
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, China
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20
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Yu Q, Wang X, Yang Y, Chi P, Huang J, Qiu S, Zheng X, Chen X. Upregulated NLGN1 predicts poor survival in colorectal cancer. BMC Cancer 2021; 21:884. [PMID: 34340665 PMCID: PMC8327451 DOI: 10.1186/s12885-021-08621-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Accepted: 07/16/2021] [Indexed: 12/14/2022] Open
Abstract
Background Neuroligin1 (NLGN1) is a main component of excitatory glutamatergic synapses complex and is important for synapse assembly and function. The clinical value of NLGN1 in colorectal cancer (CRC) is not clear. Methods We obtained the expression data of 1143 CRC patients from 3 independent Gene Expression Omnibus (GEO) datasets (GSE32323, GSE24551, GSE39582) and The Cancer Genome Atlas (TCGA) to make the comparison of the NLGN1 expression level between CRC tissues and matched noncancerous tissues, and to evaluate its value in predicting survival of CRC patients. At the protein level, these results were further confirmed by immunohistochemical staining of 52 CRC samples in our own centre. Finally, the function of NLGN1 was explored by gene set enrichment analysis (GSEA). Results Increased mRNA and protein levels of NLGN1 expression were associated with worse overall survival or recurrence-free survival in CRC patients from 2 GEO datasets, the TCGA database, and our cohort. In addition, multivariate regression analysis showed that NLGN1 was an independent poor prognostic factor of survival in patients with CRC in TCGA database (OR = 2.524, P = 0.010). Functional analysis revealed that NLGN1 was correlated with function involving the Hedgehog signaling pathway, mismatch repair process, and some material metabolism processes. Conclusions This study is the first to implicate and verify NLGN1 as a new poor prognostic marker for CRC.
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Affiliation(s)
- Qian Yu
- Department of Pathology, Union Hospital, Fujian Medical University, 29 Xin-Quan Road, Fuzhou, Fujian, 350001, People's Republic of China
| | - Xiaojie Wang
- Department of Colorectal Surgery, Union Hospital, Fujian Medical University, 29 Xin-Quan Road, Fuzhou, Fujian, 350001, People's Republic of China.
| | - Yinghong Yang
- Department of Pathology, Union Hospital, Fujian Medical University, 29 Xin-Quan Road, Fuzhou, Fujian, 350001, People's Republic of China.
| | - Pan Chi
- Department of Colorectal Surgery, Union Hospital, Fujian Medical University, 29 Xin-Quan Road, Fuzhou, Fujian, 350001, People's Republic of China
| | - Jianping Huang
- Department of Pathology, Union Hospital, Fujian Medical University, 29 Xin-Quan Road, Fuzhou, Fujian, 350001, People's Republic of China
| | - Shengliang Qiu
- Department of Pathology, Union Hospital, Fujian Medical University, 29 Xin-Quan Road, Fuzhou, Fujian, 350001, People's Republic of China
| | - Xin Zheng
- Department of Pathology, Union Hospital, Fujian Medical University, 29 Xin-Quan Road, Fuzhou, Fujian, 350001, People's Republic of China
| | - Xiaowen Chen
- Department of Pathology, Union Hospital, Fujian Medical University, 29 Xin-Quan Road, Fuzhou, Fujian, 350001, People's Republic of China
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Chattopadhyay I, Dhar R, Pethusamy K, Seethy A, Srivastava T, Sah R, Sharma J, Karmakar S. Exploring the Role of Gut Microbiome in Colon Cancer. Appl Biochem Biotechnol 2021; 193:1780-1799. [PMID: 33492552 DOI: 10.1007/s12010-021-03498-9] [Citation(s) in RCA: 74] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Accepted: 01/07/2021] [Indexed: 02/06/2023]
Abstract
Dysbiosis of the gut microbiome has been associated with the development of colorectal cancer (CRC). Gut microbiota is involved in the metabolic transformations of dietary components into oncometabolites and tumor-suppressive metabolites that in turn affect CRC development. In a healthy colon, the major of microbial metabolism is saccharolytic fermentation pathways. The alpha-bug hypothesis suggested that oncogenic bacteria such as enterotoxigenic Bacteroides fragilis (ETBF) induce the development of CRC through direct interactions with colonic epithelial cells and alterations of microbiota composition at the colorectal site. Escherichia coli, E. faecalis, F. nucleatum, and Streptococcus gallolyticus showed higher abundance whereas Bifidobacterium, Clostridium, Faecalibacterium, and Roseburia showed reduced abundance in CRC patients. The alterations of gut microbiota may be used as potential therapeutic approaches to prevent or treat CRC. Probiotics such as Lactobacillus and Bifidobacterium inhibit the growth of CRC through inhibiting inflammation and angiogenesis and enhancing the function of the intestinal barrier through the secretion of short-chain fatty acids (SCFAs). Crosstalk between lifestyle, host genetics, and gut microbiota is well documented in the prevention and treatment of CRC. Future studies are required to understand the interaction between gut microbiota and host to the influence and prevention of CRC. However, a better understanding of bacterial dysbiosis in the heterogeneity of CRC tumors should also be considered. Metatranscriptomic and metaproteomic studies are considered a powerful omic tool to understand the anti-cancer properties of certain bacterial strains. The clinical benefits of probiotics in the CRC context remain to be determined. Metagenomic approaches along with metabolomics and immunology will open a new avenue for the treatment of CRC shortly. Dietary interventions may be suitable to modulate the growth of beneficial microbiota in the gut.
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Affiliation(s)
- Indranil Chattopadhyay
- Department of Life Sciences, Central University of Tamil Nadu, Thiruvarur, Tamil Nadu, 610005, India
| | - Ruby Dhar
- Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Ansari Nagar, New Delhi, India
| | - Karthikeyan Pethusamy
- Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Ansari Nagar, New Delhi, India
| | - Ashikh Seethy
- Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Ansari Nagar, New Delhi, India
| | - Tryambak Srivastava
- Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Ansari Nagar, New Delhi, India
| | - Ramkishor Sah
- Rajendra Prasad Center for Opthalmic Sciences, AIIMS, Ansari Nagar, New Delhi, USA
| | - Jyoti Sharma
- Department of Surgical Oncology, NCI AIIMS, Jhajjar, Haryana, India
| | - Subhradip Karmakar
- Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Ansari Nagar, New Delhi, India.
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22
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Kaźmierczak-Siedlecka K, Daca A, Fic M, van de Wetering T, Folwarski M, Makarewicz W. Therapeutic methods of gut microbiota modification in colorectal cancer management - fecal microbiota transplantation, prebiotics, probiotics, and synbiotics. Gut Microbes 2020; 11:1518-1530. [PMID: 32453670 PMCID: PMC7524363 DOI: 10.1080/19490976.2020.1764309] [Citation(s) in RCA: 109] [Impact Index Per Article: 21.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
The link between gut microbiota and the development of colorectal cancer has been investigated. An imbalance in the gut microbiota promotes the progress of colorectal carcinogenesis via multiple mechanisms, including inflammation, activation of carcinogens, and tumorigenic pathways as well as damaging host DNA. Several therapeutic methods are available with which to alter the composition and the activity of gut microbiota, such as administration of prebiotics, probiotics, and synbiotics; these can confer various benefits for colorectal cancer patients. Nowadays, fecal microbiota transplantation is the most modern way of modulating the gut microbiota. Even though data regarding fecal microbiota transplantation in colorectal cancer patients are still rather limited, it has been approved as a clinical method of treatment-recurrent Clostridium difficile infection, which may also occur in these patients. The major benefits of fecal microbiota transplantation include modulation of immunotherapy efficacy, amelioration of bile acid metabolism, and restoration of intestinal microbial diversity. Nonetheless, more studies are needed to assess the long-term effects of fecal microbiota transplantation. In this review, the impact of gut microbiota on the efficiency of anti-cancer therapy and colorectal cancer patients' overall survival is also discussed.
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Affiliation(s)
- Karolina Kaźmierczak-Siedlecka
- Department of Surgical Oncology, Medical University of Gdansk, Gdańsk, Poland,CONTACT Karolina Kaźmierczak-Siedlecka ul. Smoluchowskiego 17, 80-214 Gdańsk, Poland
| | - Agnieszka Daca
- Department of Pathology and Experimental Rheumatology, Medical University of Gdansk, Gdańsk, Poland
| | - Mateusz Fic
- Department of Clinical and Molecular Biochemistry, Pomeranian Medical University Szczecin, Szczecin, Poland
| | - Thierry van de Wetering
- Department of Medical Laboratory Diagnostics - Biobank, Medical University of Gdansk, Gdańsk, Poland
| | - Marcin Folwarski
- Department of Clinical Nutrition and Dietetics, Medical University of Gdansk, Gdańsk, Poland
| | - Wojciech Makarewicz
- Department of Surgical Oncology, Medical University of Gdansk, Gdańsk, Poland
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Association of Combined Sero-Positivity to Helicobacter pylori and Streptococcus gallolyticus with Risk of Colorectal Cancer. Microorganisms 2020; 8:microorganisms8111698. [PMID: 33143263 PMCID: PMC7693002 DOI: 10.3390/microorganisms8111698] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Revised: 10/19/2020] [Accepted: 10/29/2020] [Indexed: 01/19/2023] Open
Abstract
Previously, we found that risk of colorectal cancer (CRC) is increased in individuals with serum antibody response to both Helicobacter pylori (HP) Vacuolating Cytotoxin (VacA) toxin or Streptococcus gallolyticus (SGG) pilus protein Gallo2178. In the present analysis, we tested the hypothesis that combined seropositivity to both antigens is a better indicator of CRC risk than seropositivity to single antigens. We used multiplex serologic assays to analyze pre-diagnostic serum for antibody responses from 4063 incident CRC cases and 4063 matched controls from 10 US cohorts. To examine whether combined SGG Gallo2178 and HP VacA sero-status was associated with CRC risk, we used conditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Compared to dual sero-negative individuals, there was no increased risk for individuals sero-positive to SGG Gallo2178 only (OR: 0.93; 95% CI: 0.66–1.31) or to HP VacA only (OR: 1.08; 95% CI: 0.98–1.19). However, dual sero-positive individuals had a >50% increased odds of developing CRC (OR: 1.54; 95% CI: 1.16–2.04), suggesting an interaction between antibody responses to these two pathogens and CRC risk (pinteraction = 0.06). In conclusion, this study suggests that dual sero-positivity to HP VacA and SGG Gallo2178 is an indicator of increased risk of CRC.
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Zuo Y, Jing Z, Bie M, Xu C, Hao X, Wang B. Association between Helicobacter pylori infection and the risk of colorectal cancer: A systematic review and meta-analysis. Medicine (Baltimore) 2020; 99:e21832. [PMID: 32925719 PMCID: PMC7489651 DOI: 10.1097/md.0000000000021832] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND The existing evidence on the relationship between Helicobacter pylori infection and the risk of colorectal cancer is inconsistent. We conducted a systematic review with a meta-analysis to explore this relationship and to determine whether the relationship varies according to the study characteristics. METHODS We searched the PubMed, OVID, EMBASE database, and the reference lists of pertinent articles published up to October 2019 by 2 researchers independently. Summary odds ratios (OR) with their 95% confidence intervals (CIs) were estimated using a random-effects model. RESULTS Forty seven studies including 17,416 cases of colorectal cancer (CRC) and 55,811 cases of control were included. Overall, H. pylori infection was associated with an increased risk of CRC (OR = 1.70 95% CI 1.64-1.76, I = 97%), although there was significant heterogeneity among the studies. Subgroup analysis revealed that the positive correlation might vary by the design of study conducted. CONCLUSION This meta-analysis demonstrates a positive association between H. pylori infection and the risk of colorectal cancer.
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Affiliation(s)
- Yuling Zuo
- Hospital of Chengdu University of Traditional Chinese Medicine
| | - Zhao Jing
- Hospital of Chengdu University of Traditional Chinese Medicine
| | - Mingjiang Bie
- West China fourth hospital of Public Health, Sichuan University
| | - Chunyan Xu
- J. N. Medical Laboratory, Big Data Research Center, University of Electronic Science and Technology of China
| | - Xinyu Hao
- College of Acupuncture-Moxibustion and Tuina, Chengdu University of Traditional Chinese Medicine, Sichuan
| | - Baoning Wang
- West China School of Basic medical sciences and Forensic Medicine, Sichuan University, Chengdu, China
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25
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Hang DV, Minh DT, Hoc TH, Phuoc LH, Son TQ, Le NT. H. pylori Infection and Colorectal Cancers by Anatomical Locations. Asian Pac J Cancer Prev 2020; 21:2431-2437. [PMID: 32856875 PMCID: PMC7771948 DOI: 10.31557/apjcp.2020.21.8.2431] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Indexed: 12/25/2022] Open
Abstract
Background: H. pylori infection may play a role in the development of colorectal cancers (CRC). We aimed to examine the association between H. pylori infection and the risk of CRC by anatomical locations. Methods: We conducted a case-control study on 91 incidence cases of CRC and 224 hospital controls. CRC was determined by histopathological examinations. H. pylori IgG antibody in serum was tested. We collected data on the diet, nutrition, and lifestyle by the validated semi-quantitative food frequency and demographic lifestyle questionnaire. The odds ratio and 95% confidence interval (OR (95%CI) were estimated for CRC and its subgroups. Results: Overall 54.95% of CRC cases and 42.41% of the controls were H. pylori-seropositive, OR (95%CI): 1.56 (0.88, 2.74), p for trend=0.115. Positive dose-response association in quartiles, highest vs lowest, was observed for total CRC, OR (95%CI): 2.14 (1.00, 4.58), p for trend=0.049, for proximal colon, OR (95%CI): 1.52 (0.37, 6.25), p for trend=0.571), and for distal colon and rectum cancers combined, OR (95%CI): 2.38 (1.03, 5.50), p for trend=0.039. Conclusions: There is a positive association between H. pylori and colorectal cancers, especially distal colon and rectum cancers combined, but additional research is needed to determine the underlying mechanism of chronic H. pylori infection-induced CRC in humans.
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Affiliation(s)
- Dao Viet Hang
- Department of Internal Medicine, Hanoi Medical University, Hanoi, Vietnam.,Institute of Gastroenterology and Hepatology, Hanoi, Vietnam
| | - Dinh Thi Minh
- Institute of Gastroenterology and Hepatology, Hanoi, Vietnam
| | - Tran Hieu Hoc
- Department of Surgery, Hanoi Medical University, Hanoi, Vietnam
| | - Le Hong Phuoc
- Faculty of Public Health, University of Medicine and Pharmacy at Ho Chi Minh City, Vietnam
| | - Tran Que Son
- Department of Surgery, Hanoi Medical University, Hanoi, Vietnam
| | - Ngoan Tran Le
- Institute of Research and Development, Duy Tan University, Da Nang 550000, Vietnam.,Department of Public Health, School of Medicine, International University of Health and Welfare, Japan
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26
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Luan C, Liu Z, Li Y, Dong T. Association among helicobacter pylori infection, gastrin level and colorectal cancer in patients aged 50 years and over. Pak J Med Sci 2020; 36:899-903. [PMID: 32704260 PMCID: PMC7372695 DOI: 10.12669/pjms.36.5.1993] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Objectives: To study the correlations among helicobacter pylori infection, gastrin and colorectal cancer in patients aged over 50 years old. Methods: In this study, the patients diagnosed with colorectal cancer treated in the department of digestion of our hospital together with the healthy subjects undergoing colonoscopy for health examination without pathologic findings from August 2016 to July 2019 were enrolled in colorectal cancer or control group. The blood sample was taken in fasting state, and anti-H. pylori IgG and anti-CagA antibodies as well as the level of serum gastrin were measured for all the participants. In addition, the information of each participant including age, gender, obesity, smoking history, alcohol consumption, diabetes mellitus was recorded and analyzed. Results: Four hundred and twenty-eight patients were enrolled in the colorectal group and 207 healthy subjects were enrolled in the control group. There were not significant differences in the positive rate of Ig G and Cag A and family history between the two groups (p>0.05), but there were significant differences in gastrin level, obesity, smoking history, alcohol consumption and diabetes mellitus between the two groups (p<0.05). In addition, the multivariable analysis showed that obesity, smoking history, alcoholism and diabetes mellitus have the strongest influence on the formation of colorectal cancer, while the level of gastrin didn’t show the influence. Conclusions: No significant correlations among H. pylori infection, the level of gastrin, and the occurrence of CRC in patients with a minimum age of 50 years, suggesting elder colorectal cancer patients may have a different carcinogenic mechanism from those younger patients.
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Affiliation(s)
- Chunyan Luan
- Dr. Chunyan Luan, Department of Digestion, Affiliated Yidu Central Hospital of Weifang Medical College, Qingzhou, 262500, China
| | - Zhigang Liu
- Dr. Zhigang Liu, Department of Cardiology, Affiliated Yidu Central Hospital of Weifang Medical College, Qingzhou, 262500, China
| | - Yongzhu Li
- Dr. Yongzhu Li, Department of Digestion, Affiliated Yidu Central Hospital of Weifang Medical College, Qingzhou, 262500, China
| | - Tao Dong
- Dr. Tao Dong, Department of Digestion, Affiliated Yidu Central Hospital of Weifang Medical College, Qingzhou, 262500, China
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27
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Wang M, Kong WJ, Zhang JZ, Lu JJ, Hui WJ, Liu WD, Kang XJ, Gao F. Association of Helicobacter pylori infection with colorectal polyps and malignancy in China. World J Gastrointest Oncol 2020; 12:582-591. [PMID: 32461789 PMCID: PMC7235179 DOI: 10.4251/wjgo.v12.i5.582] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2019] [Revised: 03/13/2020] [Accepted: 03/24/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Gastric Helicobacter pylori (H. pylori) infection is related to chronic gastritis, gastroduodenal ulcer, and gastric malignancies; whether this infection is related to colorectal polyps and colorectal cancer (CRC), remains debatable. AIM To investigate the relationship between gastric H. pylori infection and the risk of colorectal polyps and CRC. METHODS We retrospectively analyzed 3872 patients with colorectal polyps who underwent colonoscopy and pathological diagnosis. We also analyzed 304 patients with primary CRC. The characteristics of these patients were compared with those of the control group, which included 2362 patients with the normal intestinal mucosa. All subjects completed a 14C-urea breath test, bidirectional gastrointestinal endoscopy, and a biopsy on the same day. Data on the number, size, location, and pathology of the polyps, the location, and pathology of the CRC, the detection of H. pylori, and the incidence of H. pylori-associated atrophic gastritis or intestinal metaplasia were obtained. A logistic regression model was used to analyze the relationship between gastric infection due to H. pylori, and the incidence of colorectal polyps and CRC. RESULTS The prevalence of H. pylori infection was higher in the multiple polyps group than in the solitary polyp group and the control group [95% confidence interval (CI) = 1.02-1.31, P = 0.03; 95%CI: 2.12-2.74, P < 0.001]. The patients with adenomatous polyps had a higher incidence of H. pylori infection than patients with non-adenomatous polyps [59.95% vs 51.75%, adjusted odds ratio (OR) = 1.41, 95%CI: 1.24-1.60, P < 0.01]. Patients with H. pylori-associated atrophic gastritis or intestinal metaplasia were at high risk of CRC (adjusted OR = 3.46, 95%CI: 2.63-4.55, P < 0.01; adjusted OR = 4.86, 95%CI: 3.22-7.34, P < 0.01, respectively). The size and location of the polyps, the histopathological characteristics and the location of CRC were not related to H. pylori infection. CONCLUSION Our study demonstrates that the incidence of gastric H. pylori infection and H. pylori-associated atrophic gastritis or intestinal metaplasia elevates the risk of colorectal polyps and CRC.
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Affiliation(s)
- Man Wang
- Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Wen-Jie Kong
- Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Jing-Zhan Zhang
- Department of Dermatology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Jia-Jie Lu
- Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Wen-Jia Hui
- Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Wei-Dong Liu
- Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Xiao-Jing Kang
- Department of Dermatology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Feng Gao
- Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
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28
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Elsalem L, Jum'ah AA, Alfaqih MA, Aloudat O. The Bacterial Microbiota of Gastrointestinal Cancers: Role in Cancer Pathogenesis and Therapeutic Perspectives. Clin Exp Gastroenterol 2020; 13:151-185. [PMID: 32440192 PMCID: PMC7211962 DOI: 10.2147/ceg.s243337] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2019] [Accepted: 04/13/2020] [Indexed: 12/24/2022] Open
Abstract
The microbiota has an essential role in the pathogenesis of many gastrointestinal diseases including cancer. This effect is mediated through different mechanisms such as damaging DNA, activation of oncogenic pathways, production of carcinogenic metabolites, stimulation of chronic inflammation, and inhibition of antitumor immunity. Recently, the concept of "pharmacomicrobiomics" has emerged as a new field concerned with exploring the interplay between drugs and microbes. Mounting evidence indicates that the microbiota and their metabolites have a major impact on the pharmacodynamics and therapeutic responses toward anticancer drugs including conventional chemotherapy and molecular-targeted therapeutics. In addition, microbiota appears as an attractive target for cancer prevention and treatment. In this review, we discuss the role of bacterial microbiota in the pathogenesis of different cancer types affecting the gastrointestinal tract system. We also scrutinize the evidence regarding the role of microbiota in anticancer drug responses. Further, we discuss the use of probiotics, fecal microbiota transplantation, and antibiotics, either alone or in combination with anticancer drugs for prevention and treatment of gastrointestinal tract cancers.
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Affiliation(s)
- Lina Elsalem
- Department of Pharmacology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
| | - Ahmad A Jum'ah
- Department of Conservative Dentistry, Faculty of Dentistry, Jordan University of Science and Technology, Irbid, Jordan
| | - Mahmoud A Alfaqih
- Department of Physiology and Biochemistry, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
| | - Osama Aloudat
- Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
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29
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Dong L, Xie J, Wang Y, Zuo D. Gut Microbiota and Immune Responses. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1238:165-193. [PMID: 32323185 DOI: 10.1007/978-981-15-2385-4_10] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The gut microbiota consists of a dynamic multispecies community living within a particular niche in a mutual synergy with the host organism. Recent findings have revealed roles for the gut microbiota in the modulation of host immunity and the development and progression of immune-mediated diseases. Besides, growing evidence supports the concept that some metabolites mainly originated from gut microbiota are linked to the immune regulation implicated in systemic inflammatory and autoimmune disorders. In this chapter, we describe the recent advances in our understanding of how host-microbiota interactions shape the immune system, how they affect the pathogenesis of immune-associated diseases and the impact of these mechanisms in the efficacy of disease therapy.
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Affiliation(s)
- Lijun Dong
- The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, 510900, China
- Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China
| | - Jingwen Xie
- Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China
| | - Youyi Wang
- Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China
- School of Laboratory Medicine and Biotechnology, Institute of Molecular Immunology, Southern Medical University, Guangzhou, 510515, China
| | - Daming Zuo
- School of Laboratory Medicine and Biotechnology, Institute of Molecular Immunology, Southern Medical University, Guangzhou, 510515, China.
- Microbiome Medicine Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China.
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30
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Sabit H, Cevik E, Tombuloglu H. Colorectal cancer: The epigenetic role of microbiome. World J Clin Cases 2019; 7:3683-3697. [PMID: 31799293 PMCID: PMC6887622 DOI: 10.12998/wjcc.v7.i22.3683] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Revised: 10/23/2019] [Accepted: 10/30/2019] [Indexed: 02/05/2023] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer in men (746000 cases per year) and the second most common cancer in women globally (614000 cases per year). The incidence rate of CRC in developed countries (737000 cases per year) is higher than that in less developed countries (624000 cases per year). CRC can arise from genetic causes such as chromosomal instability and microsatellite instability. Several etiologic factors underlie CRC including age, diet, and lifestyle. Gut microbiota represent a proven cause of the disease, where they play pivotal roles in modulating and reshaping the host epigenome. Several active microbial metabolites have been found to drive carcinogenesis, invasion, and metastasis via modifying both the methylation landscape along with histone structure in intestinal cells. Gut microbiota, in response to diet, can exert both beneficial and harmful functions in humans, according to the intestinal balance of number and types of these bacteria. Although the intestinal microbial community is diverse among individuals, these microbes cumulatively produce 100-fold more proteins than the human genome itself, which calls for further studies to elaborate on the complicated interaction between these microorganisms and intestinal cells. Therefore, understanding the exact role that gut microbiota play in inducing CRC will help attain reliable strategies to precisely diagnose and treat this fatal disease.
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Affiliation(s)
- Hussein Sabit
- Department of Genetics, Institute for Medical Research and Consultations, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia
| | - Emre Cevik
- Department of Genetics, Institute for Medical Research and Consultations, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia
| | - Huseyin Tombuloglu
- Department of Genetics, Institute for Medical Research and Consultations, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia
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31
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Tarashi S, Siadat SD, Ahmadi Badi S, Zali M, Biassoni R, Ponzoni M, Moshiri A. Gut Bacteria and their Metabolites: Which One Is the Defendant for Colorectal Cancer? Microorganisms 2019; 7:E561. [PMID: 31766208 PMCID: PMC6920974 DOI: 10.3390/microorganisms7110561] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2019] [Revised: 08/22/2019] [Accepted: 09/04/2019] [Indexed: 12/12/2022] Open
Abstract
Colorectal cancer (CRC) is a worldwide health concern which requires efficient therapeutic strategies. The mechanisms underlying CRC remain an essential subject of investigations in the cancer biology field. The evaluation of human microbiota can be critical in this regard, since the disruption of the normal community of gut bacteria is an important issue in the development of CRC. However, several studies have already evaluated the different aspects of the association between microbiota and CRC. The current study aimed at reviewing and summarizing most of the studies on the modifications of gut bacteria detected in stool and tissue samples of CRC cases. In addition, the importance of metabolites derived from gut bacteria, their relationship with the microbiota, and epigenetic modifications have been evaluated.
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Affiliation(s)
- Samira Tarashi
- Microbiology Research Center, Pasteur Institute of Iran, 1316943551 Tehran, Iran; (S.T.); (S.D.S.); (S.A.B.)
- Mycobacteriology and Pulmonary Research Department, Pasteur Institute of Iran, 1316943551 Tehran, Iran
| | - Seyed Davar Siadat
- Microbiology Research Center, Pasteur Institute of Iran, 1316943551 Tehran, Iran; (S.T.); (S.D.S.); (S.A.B.)
- Mycobacteriology and Pulmonary Research Department, Pasteur Institute of Iran, 1316943551 Tehran, Iran
| | - Sara Ahmadi Badi
- Microbiology Research Center, Pasteur Institute of Iran, 1316943551 Tehran, Iran; (S.T.); (S.D.S.); (S.A.B.)
- Mycobacteriology and Pulmonary Research Department, Pasteur Institute of Iran, 1316943551 Tehran, Iran
| | - Mohammadreza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, 19857-17411 Tehran, Iran;
| | - Roberto Biassoni
- Laboratory of Molecular Medicine, IRCCS Instituto Giannina Gaslini, 16147 Genova, Italy;
| | - Mirco Ponzoni
- Laboratory of Experimental Therapies in Oncology, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy
| | - Arfa Moshiri
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, 19857-17411 Tehran, Iran;
- Laboratory of Experimental Therapies in Oncology, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy
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32
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Yang L, Zhang J, Xu J, Wei X, Yang J, Liu Y, Li H, Zhao C, Wang Y, Zhang L, Gai Z. Helicobacter pylori Infection Aggravates Dysbiosis of Gut Microbiome in Children With Gastritis. Front Cell Infect Microbiol 2019; 9:375. [PMID: 31781514 PMCID: PMC6859803 DOI: 10.3389/fcimb.2019.00375] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Accepted: 10/16/2019] [Indexed: 02/06/2023] Open
Abstract
Introduction:Helicobacter pylori infection consistently leads to chronic and low degree of inflammatory response in gastric mucosa and is closely related with gastrointestinal and extra-gastric diseases. Effects of local microbiome in the stomach have been studied in adults and children with H. pylori infection. It is, however, not known whether the intestinal microbial community differs in children with varying H. pylori infection. The aim of this study is to characterize the altered composition of microbiome induced by H. pylori infection and in gastritis. Materials and Methods: This study involved 154 individuals, including 50 children affected by H. pylori-induced gastritis, 42 children with H. pylori-negative gastritis, and 62 healthy controls. Gut microbiome composition was analyzed using 16S rRNA gene-based pyrosequencing. Fecal bacterial diversity and composition were then compared. Results: On the basis of an analysis of similarities and differences, we found that children with H. pylori-induced gastritis exhibited gut bacteria dysbiosis. The ratio of Firmicutes/Bacteroidetes (F:B) at the phylum level had dramatically decreased in H. pylori-positive gastritis group (HPG) and H. pylori-negative gastritis group (HNG), compared with the healthy control group (HCG). At the family and genus levels, relative abundance of Bacteroidaceae and Enterobacteriaceae was prevalent in HPG and HNG, whereas relative abundance of Lachnospiraceae, Bifidobacteriaceae, and Lactobacillaceae was seen in HCG. Prevalence of different taxa of gut microbiome at the class, order, family, and genus levels was also observed among the three groups. Conclusions: Gastritis can cause changes in composition of fecal microbiome, which is exacerbated by H. pylori infection. These changes in gut microbiome may be related to drug resistance and development of chronic gastrointestinal diseases.
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Affiliation(s)
- Lu Yang
- Department of Digestive Disease, Qilu Children's Hospital of Shandong University, Jinan, China
| | - Jiaming Zhang
- Shandong Children's Microbiome Center, Qilu Children's Hospital of Shandong University, Jinan, China
| | - Junjie Xu
- Department of Digestive Disease, Qilu Children's Hospital of Shandong University, Jinan, China
| | - Xuxia Wei
- Department of Digestive Disease, Qilu Children's Hospital of Shandong University, Jinan, China
| | - Junjie Yang
- College of Life Science, Qilu Normal University, Jinan, China
| | - Yi Liu
- Shandong Children's Microbiome Center, Qilu Children's Hospital of Shandong University, Jinan, China.,Research Institute of Pediatrics, Qilu Children's Hospital of Shandong University, Jinan, China
| | - Hua Li
- Department of Digestive Disease, Qilu Children's Hospital of Shandong University, Jinan, China
| | - Changying Zhao
- Shandong Children's Microbiome Center, Qilu Children's Hospital of Shandong University, Jinan, China
| | - Ying Wang
- Shandong Children's Microbiome Center, Qilu Children's Hospital of Shandong University, Jinan, China.,Research Institute of Pediatrics, Qilu Children's Hospital of Shandong University, Jinan, China
| | - Lei Zhang
- Shandong Children's Microbiome Center, Qilu Children's Hospital of Shandong University, Jinan, China.,Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Beijing, China
| | - Zhongtao Gai
- Shandong Children's Microbiome Center, Qilu Children's Hospital of Shandong University, Jinan, China.,Research Institute of Pediatrics, Qilu Children's Hospital of Shandong University, Jinan, China
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Dai Z, Zhang J, Wu Q, Chen J, Liu J, Wang L, Chen C, Xu J, Zhang H, Shi C, Li Z, Fang H, Lin C, Tang D, Wang D. The role of microbiota in the development of colorectal cancer. Int J Cancer 2019; 145:2032-2041. [PMID: 30474116 PMCID: PMC6899977 DOI: 10.1002/ijc.32017] [Citation(s) in RCA: 84] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2018] [Revised: 10/25/2018] [Accepted: 11/13/2018] [Indexed: 02/05/2023]
Abstract
Colorectal cancer is the third largest cancer in worldwide and has been proven to be closely related to the intestinal microbiota. Many reports and clinical studies have shown that intestinal microbial behavior may lead to pathological changes in the host intestines. The changes can be divided into epigenetic changes and carcinogenic changes at the gene level, which ultimately promote the production and development of colorectal cancer. This article reviews the pathways of microbial signaling in the intestinal epithelial barrier, the role of microbiota in inflammatory colorectal tumors, and typical microbial carcinogenesis. Finally, by gaining a deeper understanding of the intestinal microbiota, we hope to achieve the goal of treating colorectal cancer using current microbiota technologies, such as fecal microbiological transplantation.
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Affiliation(s)
- Zhujiang Dai
- Clinical Medical CollegeYangzhou UniversityYangzhouJiangsu ProvinceChina
| | - Jingqiu Zhang
- Department of General SurgeryInstitute of General Surgery, Clinical Medical College, Yangzhou University, Northern Jiangsu People's HospitalYangzhouChina
| | - Qi Wu
- Clinical Medical CollegeYangzhou UniversityYangzhouJiangsu ProvinceChina
| | - Juan Chen
- Department of GastroenterologyClinical Medical College, Yangzhou University, Northern Jiangsu People's HospitalYangzhouChina
| | - Jun Liu
- Department of GastroenterologyClinical Medical College, Yangzhou University, Northern Jiangsu People's HospitalYangzhouChina
| | - Lu Wang
- Department of GastroenterologyClinical Medical College, Yangzhou University, Northern Jiangsu People's HospitalYangzhouChina
| | - Chaowu Chen
- Department of GastroenterologyClinical Medical College, Yangzhou University, Northern Jiangsu People's HospitalYangzhouChina
| | - Jiaming Xu
- Department of General SurgeryInstitute of General Surgery, Clinical Medical College, Yangzhou University, Northern Jiangsu People's HospitalYangzhouChina
| | - Hongpeng Zhang
- Department of General SurgeryInstitute of General Surgery, Clinical Medical College, Yangzhou University, Northern Jiangsu People's HospitalYangzhouChina
| | - Chunfeng Shi
- Clinical Medical CollegeYangzhou UniversityYangzhouJiangsu ProvinceChina
| | - Zhen Li
- Clinical Medical CollegeYangzhou UniversityYangzhouJiangsu ProvinceChina
| | - Huiwen Fang
- Clinical Medical CollegeYangzhou UniversityYangzhouJiangsu ProvinceChina
| | - Chaobiao Lin
- Clinical Medical CollegeYangzhou UniversityYangzhouJiangsu ProvinceChina
| | - Dong Tang
- Department of General SurgeryInstitute of General Surgery, Clinical Medical College, Yangzhou University, Northern Jiangsu People's HospitalYangzhouChina
| | - Daorong Wang
- Department of General SurgeryInstitute of General Surgery, Clinical Medical College, Yangzhou University, Northern Jiangsu People's HospitalYangzhouChina
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Panebianco C, Potenza A, Andriulli A, Pazienza V. Exploring the microbiota to better understand gastrointestinal cancers physiology. Clin Chem Lab Med 2019; 56:1400-1412. [PMID: 29630505 DOI: 10.1515/cclm-2017-1163] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2017] [Accepted: 02/26/2018] [Indexed: 02/07/2023]
Abstract
Gastrointestinal cancers account for around 40% of cancer-related deaths worldwide, representing a global health burden. There is a growing body of evidence highlighting the link between microbiota and gastrointestinal tumorigenesis and/or resistance to therapy. In the present manuscript, we reviewed the published studies on the relationship between the microbiota and the different gastrointestinal tumors, namely, gastric, colorectal and esophageal, including also the cancer of accessory organs such as liver and pancreas. There is an emergent interest in the manipulation of gastrointestinal microflora in order to understand the gastrointestinal tumorigenesis' processes and the establishment of chemoresistance mechanisms.
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Affiliation(s)
- Concetta Panebianco
- Gastroenterology Unit, IRCCS "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo (FG), Italy
| | - Adele Potenza
- Dietetic and Clinical Nutrition Unit IRCCS "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo (FG), Italy
| | - Angelo Andriulli
- Gastroenterology Unit, IRCCS "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo (FG), Italy
| | - Valerio Pazienza
- Gastroenterology Unit, IRCCS "Casa Sollievo della Sofferenza" Hospital, Viale dei Cappuccini, 1, 71013 San Giovanni Rotondo (FG), Italy, Phone: +39-0882.416281, Fax: +39-0882.410271
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35
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Kountouras J, Polyzos SA, Doulberis M, Zeglinas C, Artemaki F, Vardaka E, Deretzi G, Giartza-Taxidou E, Tzivras D, Vlachaki E, Kazakos E, Katsinelos P, Mantzoros CS. Potential impact of Helicobacter pylori-related metabolic syndrome on upper and lower gastrointestinal tract oncogenesis. Metabolism 2018; 87:18-24. [PMID: 29936174 DOI: 10.1016/j.metabol.2018.06.008] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Revised: 06/18/2018] [Accepted: 06/19/2018] [Indexed: 12/12/2022]
Abstract
Both Helicobacter pylori infection and metabolic syndrome present significant global public health burdens. Metabolic syndrome is closely related to insulin resistance, the major underlying mechanism responsible for metabolic abnormalities, and Helicobacter pylori infection has been proposed to be a contributing factor. There is growing evidence for a potential association between Helicobacter pylori infection and insulin resistance, metabolic syndrome and related morbidity, including abdominal obesity, type 2 diabetes mellitus, dyslipidemia, hypertension, all of which increase mortality related to cardio-cerebrovascular disease, neurodegenerative disorders, nonalcoholic fatty liver disease and malignancies. More specifically, insulin resistance, metabolic syndrome and hyperinsulinemia have been associated with upper and lower gastrointestinal tract oncogenesis. Apart from cardio-cerebrovascular, degenerative diseases and nonalcoholic fatty liver disease, a number of studies claim that Helicobacter pylori infection is implicated in metabolic syndrome-related Barrett's esophagus and esophageal adenocarcinoma development, gastric and duodenal ulcers and gastric oncogenesis as well as lower gastrointestinal tract oncogenesis. This review summarizes evidence on the potential impact of Helicobacter pylori-related metabolic syndrome on gastroesophageal reflux disease-Barrett's esophagus-esophageal adenocarcinoma, gastric atrophy-intestinal metaplasia-dysplasia-gastric cancer and colorectal adenoma-dysplasia-colorectal cancer sequences. Helicobacter pylori eradication might inhibit these oncogenic processes, and thus further studies are warranted.
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Affiliation(s)
- Jannis Kountouras
- Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece.
| | - Stergios A Polyzos
- First Department of Pharmacology, Department of Medicine, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece
| | - Michael Doulberis
- Division of General Internal Medicine, University Hospital Inselspital of Bern, 3010 Bern, Switzerland
| | - Christos Zeglinas
- Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece
| | - Fotini Artemaki
- Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece
| | - Elizabeth Vardaka
- Department of Nutrition and Dietetics, Alexander Technological Educational Institute, Thessaloniki, Sindos, Macedonia, Greece
| | - Georgia Deretzi
- Department of Neurology, Papageorgiou General Hospital, Thessaloniki, Macedonia, Greece
| | | | | | - Efthymia Vlachaki
- Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece
| | - Evangelos Kazakos
- Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece
| | - Panagiotis Katsinelos
- Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece
| | - Christos S Mantzoros
- Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
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Mendonça LABM, Dos Santos Ferreira R, de Cássia Avellaneda Guimarães R, de Castro AP, Franco OL, Matias R, Carvalho CME. The Complex Puzzle of Interactions Among Functional Food, Gut Microbiota, and Colorectal Cancer. Front Oncol 2018; 8:325. [PMID: 30234008 PMCID: PMC6133950 DOI: 10.3389/fonc.2018.00325] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2018] [Accepted: 07/30/2018] [Indexed: 12/18/2022] Open
Abstract
Colorectal cancer exerts a strong influence on the epidemiological panorama worldwide, and it is directly correlated to etiologic factors that are substantiated by genetic and environmental elements. This complex mixture of factors also has a relationship involving the structural dependence and composition of the gut microbiome, leading to a dysbacteriosis process that may evolve to serious modifications in the intestinal lining, eventually causing the development of a neoplasm. The gastrointestinal tract presents defense strategies and immunological properties that interfere in intestinal permeability, inhibiting the bacterial translocation, thus maintaining the integrity of intestinal homeostasis. The modulation of the intestinal microbiome and the extinction of risk factors associated with intestinal balance losses, especially of environmental factors, make cell and defense alterations impossible. This modulation may be conducted by means of functional foods in the diet, especially soluble fibers, polyunsaturated fatty acids, antioxidants and prebiotics that signal immunomodulatory effects in the intestinal microbiota, with preventive and therapeutic action for colorectal cancer. In summary, this review focuses on the importance of dietary modulation of the intestinal microbiota as an instrument for dysbacteriosis and, consequently, for the prevention of colorectal cancer, suggesting anticarcinogenic, and antiangiogenic properties. Among the intestinal modulating agents considered here are functional foods, especially flaxseed, oat and soy, composing a Bioactive Food Compound.
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Affiliation(s)
- Lígia A B M Mendonça
- S-Inova Biotech Post Graduate Program in Biotechnology, Catholic University Dom Bosco, Campo Grande, Brazil
| | - Rosângela Dos Santos Ferreira
- Post Graduate Program in Health and Development in the Central-West Region of Brazil, Federal University of Mato Grosso do Sul, Campo Grande, Brazil
| | - Rita de Cássia Avellaneda Guimarães
- Post Graduate Program in Health and Development in the Central-West Region of Brazil, Federal University of Mato Grosso do Sul, Campo Grande, Brazil
| | - Alinne P de Castro
- S-Inova Biotech Post Graduate Program in Biotechnology, Catholic University Dom Bosco, Campo Grande, Brazil
| | - Octávio L Franco
- S-Inova Biotech Post Graduate Program in Biotechnology, Catholic University Dom Bosco, Campo Grande, Brazil.,Center of Proteomic and Biochemical Analysis, Post Graduate Program in Genomic Sciences and Biotechnology, Catholic University of Brasilia, Brasilia, Brazil
| | - Rosemary Matias
- Post Graduate Program in Environmental Sciences and Agricultural Sustainability, Catholic University Dom Bosco, Campo Grande, Brazil.,Post Graduate Program in Environment and Regional Development, University Anhanguera Uniderp, Campo Grande, Brazil
| | - Cristiano M E Carvalho
- S-Inova Biotech Post Graduate Program in Biotechnology, Catholic University Dom Bosco, Campo Grande, Brazil.,Post Graduate Program in Environment and Regional Development, University Anhanguera Uniderp, Campo Grande, Brazil
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Park H, Park JJ, Park YM, Baik SJ, Lee HJ, Jung DH, Kim JH, Youn YH, Park H. The association between Helicobacter pylori infection and the risk of advanced colorectal neoplasia may differ according to age and cigarette smoking. Helicobacter 2018; 23:e12477. [PMID: 29600573 DOI: 10.1111/hel.12477] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND The association between Helicobacter pylori infection and advanced colorectal neoplasia (ACN) remains controversial. This study aimed to clarify the association between H. pylori infection and ACN according to age groups. METHODS We retrospectively analyzed the association between H. pylori infection and ACN in patients aged <50 and ≥50 years receiving a health checkup that included colonoscopy. Helicobacter pylori positivity was determined by the results of serum anti-H. pylori immunoglobulin G or rapid urease test, if the anti-H. pylori immunoglobulin G was in the borderline range. RESULTS Among the 19 337 patients who were included, 56.2% and 3.4% were positive for H. pylori and ACN, respectively. Helicobacter pylori infection independently increased the risk of ACN in patients aged <50 years (odds ratio [OR], 1.602; 95% confidence intervals [CI], 1.194-2.150) but not in patients aged ≥50 years (OR, 1.046; 95% CI, 0.863-1.268). The positive association between H. pylori infection and ACN was affected by smoking history. When stratified by age and smoking history, H. pylori infection conferred an increased risk of ACN in patients aged <50 years with a history of smoking (OR, 1.926; 95% CI, 1.336-2.775) but not in the other 3 groups (3-way interaction test P = .023). Among patients aged <50 years with ACN, ACN in the left colon was found more frequently in patients with H. pylori infection and a history of smoking than in those without (69.3% vs 54.4%, respectively; P = .031). CONCLUSIONS Helicobacter pylori infection confers an increased risk of ACN, but the association may differ according to age and smoking history.
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Affiliation(s)
- Hyunsung Park
- Division of Gastroenterology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Jun Park
- Division of Gastroenterology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Yoo Mi Park
- Health Promotion Center, Institute of Gastroenterology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Su Jung Baik
- Health Promotion Center, Institute of Gastroenterology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Hyun Ju Lee
- Health Promotion Center, Institute of Gastroenterology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Da Hyun Jung
- Division of Gastroenterology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jie-Hyun Kim
- Division of Gastroenterology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Young Hoon Youn
- Division of Gastroenterology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Hyojin Park
- Division of Gastroenterology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
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Liu WZ, Xie Y, Lu H, Cheng H, Zeng ZR, Zhou LY, Chen Y, Wang JB, Du YQ, Lu NH. Fifth Chinese National Consensus Report on the management of Helicobacter pylori infection. Helicobacter 2018; 23:e12475. [PMID: 29512258 DOI: 10.1111/hel.12475] [Citation(s) in RCA: 324] [Impact Index Per Article: 46.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Since the 'Fourth Chinese National Consensus Report on the management of H. pylori infection' was published in 2012, three important consensuses (Kyoto global consensus report on H. pylori gastritis, The Toronto Consensus for the Treatment of H. pylori Infection in Adults and Management of H. pylori infection-the Maastricht V/Florence Consensus Report) have been published regarding the management of H. pylori infection. MATERIALS AND METHODS A Delphi method was adopted to develop the consensus of relevant 'statements'. First, the established 'statements' were sent to experts via email. Second, after undergoing two rounds of consultation, the initial statements were discussed face to face and revised in the conference item by item on 16 December 2016. Finally, 21 core members of conferees participated in the final vote of statements. Voting for each statement was performed using an electronic system with levels of agreements shown on the screen in real time. RESULTS Consensus contents contained a total of 48 "statements" and related 6 parts, including indications for H. pylori eradication, diagnosis, treatment, H. pylori and gastric cancer, H. pylori infection in special populations, H. pylori and gastrointestinal microbiota. CONCLUSIONS Recommendations are provided on the basis of the best available evidence.
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Affiliation(s)
- Wen Zhong Liu
- Department of Gastroenterology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yong Xie
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Hong Lu
- Department of Gastroenterology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hong Cheng
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Zhi Rong Zeng
- Division of Gastroenterology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China
| | - Li Ya Zhou
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Ye Chen
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China
| | - Jiang Bin Wang
- Department of Gastroenterology, China-Japan Friendship Hospital, Jilin University, Changchun, Jilin Province, China
| | - Yi Qi Du
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Nong Hua Lu
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
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Maisonneuve C, Irrazabal T, Martin A, Girardin SE, Philpott DJ. The Impact of the Gut Microbiome on Colorectal Cancer. ANNUAL REVIEW OF CANCER BIOLOGY-SERIES 2018. [DOI: 10.1146/annurev-cancerbio-030617-050240] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Charles Maisonneuve
- Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada;,
| | - Thergiory Irrazabal
- Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada;,
| | - Alberto Martin
- Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada;,
| | - Stephen E. Girardin
- Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada;,
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada
| | - Dana J. Philpott
- Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada;,
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40
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Farhana L, Banerjee HN, Verma M, Majumdar APN. Role of Microbiome in Carcinogenesis Process and Epigenetic Regulation of Colorectal Cancer. Methods Mol Biol 2018; 1856:35-55. [PMID: 30178245 DOI: 10.1007/978-1-4939-8751-1_3] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
Epigenetic changes during the development of colorectal cancer (CRC) play a significant role. Along with factors such as diet, lifestyle, and genetics, oncogenic infection, bacteria alone or whole microbiome, has been associated with this tumor type. How gut microbiome contributes to CRC pathogenesis in the host is not fully understood. Most of the epigenetic studies in CRC have been conducted in populations infected with Helicobacter pylori. In the current review, we summarize how the gut microbiota contributes in colon carcinogenesis and the potential role of epigenetic mechanism in gene regulation. We discuss microbiota-mediated initiation and progression of colon tumorigenesis and have also touched upon the role of microbial metabolites as an initiator or an inhibitor for procarcinogenic or antioncogenic activities. The hypothesis of gut microbiota associated CRC revealed the dynamic and complexity of microbial interaction in initiating the development of CRC. In the multifaceted processes of colonic carcinogenesis, gradual alteration of microbiota along with their microenvironment and the potential oncopathogenic microbes mediated modulation of cancer therapy and other factors involved in microbiome dysbiosis leading to the CRC have also been discussed. This review provides a comprehensive summary of the mechanisms of CRC development, the role of microbiome or single bacterial infection in regulating the processes of carcinogenesis, and the intervention by novel therapeutics. Epigenetic mechanism involved in CRC is also discussed.
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Affiliation(s)
- Lulu Farhana
- Veterans Affairs Medical Center, Research Service, Detroit, MI, USA
- Department of Internal Medicine, Wayne State University, Detroit, MI, USA
| | | | - Mukesh Verma
- Epidemiology and Genomics Research Program, National Cancer Institute, Rockville, MD, USA
| | - Adhip P N Majumdar
- Veterans Affairs Medical Center, Research Service, Detroit, MI, USA.
- Department of Internal Medicine, Wayne State University, Detroit, MI, USA.
- Karmanos Cancer Institute, Wayne State University-School of Medicine, Detroit, MI, USA.
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Fernández de Larrea-Baz N, Michel A, Romero B, Pérez-Gómez B, Moreno V, Martín V, Dierssen-Sotos T, Jiménez-Moleón JJ, Castilla J, Tardón A, Ruiz I, Peiró R, Tejada A, Chirlaque MD, Butt JA, Olmedo-Requena R, Gómez-Acebo I, Linares P, Boldo E, Castells A, Pawlita M, Castaño-Vinyals G, Kogevinas M, de Sanjosé S, Pollán M, Del Campo R, Waterboer T, Aragonés N. Helicobacter pylori Antibody Reactivities and Colorectal Cancer Risk in a Case-control Study in Spain. Front Microbiol 2017; 8:888. [PMID: 28611733 PMCID: PMC5447227 DOI: 10.3389/fmicb.2017.00888] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2016] [Accepted: 05/02/2017] [Indexed: 12/19/2022] Open
Abstract
Background: Several studies have suggested that Helicobacter pylori (H. pylori) infection is a risk factor for colorectal cancer (CRC), while others have not confirmed this hypothesis. This work aimed to assess the relation of CRC with H. pylori seropositivity and with seropositivity to 16 H. pylori proteins, in the MultiCase-Control study, MCC-Spain. Methods: MCC-Spain is a multicase-control study carried out in Spain from 2008 to 2013. In total, 2,140 histologically-confirmed incident CRC cases and 4,098 population-based controls were recruited. Controls were frequency-matched by sex, age, and province. Epidemiological data were collected through a questionnaire fulfilled by face-to-face interviews and a self-administered food-frequency questionnaire. Seroreactivities against 16 H. pylori proteins were determined in 1,488 cases and 2,495 controls using H. pylori multiplex serology. H. pylori seropositivity was defined as positivity to ≥4 proteins. Multivariable logistic regression mixed models were used to estimate odds ratios (OR) and 95% confidence intervals (CI). Results:H. pylori seropositivity was not associated with increased CRC risk (OR = 0.91; 95% CI: 0.71–1.16). Among H. pylori seropositive subjects, seropositivity to Cagδ showed a lower CRC risk, and risk decreased with increasing number of proteins seropositive. Seropositivity to the most recognized virulence factors, CagA and VacA, was not associated with a higher CRC risk. No statistically significant heterogeneity was identified among tumor sites, although inverse relations were stronger for left colon cancer. An interaction with age and sex was found: H. pylori seropositivity was associated with a lower CRC risk in men younger than 65 and with a higher risk in older women. Conclusions: Our results suggest that neither H. pylori seropositivity, nor seropositivity to the virulence factor CagA are associated with a higher CRC risk. A possible effect modification by age and sex was identified.
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Affiliation(s)
- Nerea Fernández de Larrea-Baz
- Environmental and Cancer Epidemiology Area, National Center of Epidemiology, Instituto de Salud Carlos IIIMadrid, Spain.,Consortium for Biomedical Research in Epidemiology and Public Health (CIBER of Epidemiology and Public Health) - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)Madrid, Spain
| | - Angelika Michel
- Division of Molecular Diagnostics of Oncogenic Infections, Infection, Inflammation and Cancer Program, German Cancer Research Center (DKFZ)Heidelberg, Germany
| | - Beatriz Romero
- Department of Microbiology, Ramón y Cajal University Hospital (IRYCIS)Madrid, Spain
| | - Beatriz Pérez-Gómez
- Environmental and Cancer Epidemiology Area, National Center of Epidemiology, Instituto de Salud Carlos IIIMadrid, Spain.,Consortium for Biomedical Research in Epidemiology and Public Health (CIBER of Epidemiology and Public Health) - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)Madrid, Spain.,Cancer Epidemiology Research Group, Oncology and Hematology Area, IIS Puerta de Hierro (Puerta de Hierro Health Research Institute)Madrid, Spain
| | - Victor Moreno
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBER of Epidemiology and Public Health) - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)Madrid, Spain.,Cancer Prevention and Control Program, Catalan Institute of OncologyHospitalet de Llobregat, Spain.,Department of Clinical Sciences, Faculty of Medicine, University of BarcelonaBarcelona, Spain.,Colorectal Cancer Group, Bellvitge Biomedical Research Institute (IDIBELL)Hospitalet de Llobregat, Spain
| | - Vicente Martín
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBER of Epidemiology and Public Health) - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)Madrid, Spain.,The Research Group in Gene - Environment and Health Interactions, University of LeónLeón, Spain.,Area of Preventive Medicine and Public Health, Faculty of Health Sciences, Department of Biomedical Sciences, University of LeónLeón, Spain
| | - Trinidad Dierssen-Sotos
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBER of Epidemiology and Public Health) - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)Madrid, Spain.,Division of Epidemiology and Computational Biology, School of Medicine, University of Cantabria-IDIVALSantander, Spain
| | - José J Jiménez-Moleón
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBER of Epidemiology and Public Health) - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)Madrid, Spain.,Granada Health Research Institute (ibs.GRANADA) - Instituto de Investigación Biosanitaria de GranadaGranada, Spain.,Department of Preventive Medicine and Public Health, University of GranadaGranada, Spain
| | - Jesús Castilla
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBER of Epidemiology and Public Health) - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)Madrid, Spain.,Instituto de Salud Pública de Navarra, IdiSNA-Navarra Institute for Health ResearchPamplona, Spain
| | - Adonina Tardón
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBER of Epidemiology and Public Health) - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)Madrid, Spain.,Molecular Epidemiology of Cancer Unit, Oncology Institute, Department of Medicine, University of OviedoOviedo, Spain
| | - Irune Ruiz
- Department of Pathology, Donostia University HospitalDonostia, Spain
| | - Rosana Peiró
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBER of Epidemiology and Public Health) - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)Madrid, Spain.,Foundation for the Promotion of Health and Biomedical Research of Valencia Region (FISABIO) - Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana FISABIO-Salud PúblicaValencia, Spain
| | - Antonio Tejada
- Coloproctology Unit, Department of General Surgery, Huelva University Hospital ComplexHuelva, Spain
| | - María D Chirlaque
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBER of Epidemiology and Public Health) - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)Madrid, Spain.,Department of Epidemiology, Regional Health Council, IMIB-ArrixacaMurcia, Spain.,Department of Health and Social Sciences, University of MurciaMurcia, Spain
| | - Julia A Butt
- Division of Molecular Diagnostics of Oncogenic Infections, Infection, Inflammation and Cancer Program, German Cancer Research Center (DKFZ)Heidelberg, Germany
| | - Rocío Olmedo-Requena
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBER of Epidemiology and Public Health) - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)Madrid, Spain.,Granada Health Research Institute (ibs.GRANADA) - Instituto de Investigación Biosanitaria de GranadaGranada, Spain.,Department of Preventive Medicine and Public Health, University of GranadaGranada, Spain
| | - Inés Gómez-Acebo
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBER of Epidemiology and Public Health) - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)Madrid, Spain.,Division of Epidemiology and Computational Biology, School of Medicine, University of Cantabria-IDIVALSantander, Spain
| | - Pedro Linares
- Department of Gastroenterology and Hepatology, Complejo Asistencial Universitario de LeónLeón, Spain
| | - Elena Boldo
- Environmental and Cancer Epidemiology Area, National Center of Epidemiology, Instituto de Salud Carlos IIIMadrid, Spain.,Consortium for Biomedical Research in Epidemiology and Public Health (CIBER of Epidemiology and Public Health) - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)Madrid, Spain.,Cancer Epidemiology Research Group, Oncology and Hematology Area, IIS Puerta de Hierro (Puerta de Hierro Health Research Institute)Madrid, Spain
| | - Antoni Castells
- Gastroenterology Department, Hospital ClínicBarcelona, Spain.,Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)Barcelona, Spain.,CIBER Liver and Digestive Diseases - CIBER Enfermedades Hepáticas y Digestivas (CIBEREHD)Madrid, Spain.,Department of Gastroenterology, University of BarcelonaBarcelona, Spain
| | - Michael Pawlita
- Division of Molecular Diagnostics of Oncogenic Infections, Infection, Inflammation and Cancer Program, German Cancer Research Center (DKFZ)Heidelberg, Germany
| | - Gemma Castaño-Vinyals
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBER of Epidemiology and Public Health) - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)Madrid, Spain.,ISGlobal, Centre for Research in Environmental Epidemiology (CREAL)Barcelona, Spain.,Hospital del Mar Medical Research Institute (IMIM)Barcelona, Spain.,Department of Experimental and Health Sciences, Universitat Pompeu FabraBarcelona, Spain
| | - Manolis Kogevinas
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBER of Epidemiology and Public Health) - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)Madrid, Spain.,ISGlobal, Centre for Research in Environmental Epidemiology (CREAL)Barcelona, Spain.,Hospital del Mar Medical Research Institute (IMIM)Barcelona, Spain.,Department of Experimental and Health Sciences, Universitat Pompeu FabraBarcelona, Spain
| | - Silvia de Sanjosé
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBER of Epidemiology and Public Health) - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)Madrid, Spain.,Cancer Epidemiology and Research Program, Catalan Institute of Oncology-IDIBELLHospitalet de Llobregat, Spain
| | - Marina Pollán
- Environmental and Cancer Epidemiology Area, National Center of Epidemiology, Instituto de Salud Carlos IIIMadrid, Spain.,Consortium for Biomedical Research in Epidemiology and Public Health (CIBER of Epidemiology and Public Health) - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)Madrid, Spain.,Cancer Epidemiology Research Group, Oncology and Hematology Area, IIS Puerta de Hierro (Puerta de Hierro Health Research Institute)Madrid, Spain
| | - Rosa Del Campo
- Department of Microbiology, Ramón y Cajal University Hospital (IRYCIS)Madrid, Spain.,Spanish Network for Research in Infectious Diseases - Red Española de Investigación en Patología InfecciosaSevilla, Spain
| | - Tim Waterboer
- Division of Molecular Diagnostics of Oncogenic Infections, Infection, Inflammation and Cancer Program, German Cancer Research Center (DKFZ)Heidelberg, Germany
| | - Nuria Aragonés
- Environmental and Cancer Epidemiology Area, National Center of Epidemiology, Instituto de Salud Carlos IIIMadrid, Spain.,Consortium for Biomedical Research in Epidemiology and Public Health (CIBER of Epidemiology and Public Health) - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)Madrid, Spain
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Blase JL, Campbell PT, Gapstur SM, Pawlita M, Michel A, Waterboer T, Teras LR. Prediagnostic Helicobacter pylori Antibodies and Colorectal Cancer Risk in an Elderly, Caucasian Population. Helicobacter 2016; 21:488-492. [PMID: 27006167 DOI: 10.1111/hel.12305] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Study results on overall seroprevalence of Helicobacter pylori and colorectal cancer risk have been inconsistent. However, one study found positive associations with antibodies to specific H. pylori proteins. To follow up on those findings, we assessed associations of 15 H. pylori specific proteins with colorectal cancer incidence in the prospective Cancer Prevention Study-II Nutrition Cohort. MATERIALS AND METHODS Participants in this nested case-control study included 392 cases and 774 controls who were predominantly elderly (median age at blood draw: 71 years) and Caucasian (98%). Seroreactivity against 15 H. pylori proteins was assessed by fluorescent bead-based multiplex serology and associations with colorectal cancer were estimated using conditional logistic regression. RESULTS Helicobacter pylori serostatus was not associated with colorectal cancer incidence (odds ratio (OR), 1.17, 95% confidence interval (95% CI), 0.91-1.50). Among individual antigens, GroEl serostatus was associated with colorectal cancer risk (OR, 1.32, 95% CI: 1.03-1.70), whereas CagM was associated with colon cancer risk only (OR, 1.35, 95% CI: 1.01-1.80). No dose-response relationships were observed for any of the antigens, including GroEl and CagM. CONCLUSIONS The results of our study do not support an association between H. pylori infection and colorectal cancer risk in this elderly, mostly Caucasian population.
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Affiliation(s)
- Jennifer L Blase
- Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA
| | - Peter T Campbell
- Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA
| | - Susan M Gapstur
- Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA
| | - Michael Pawlita
- Infection, Inflammation and Cancer Program, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Angelika Michel
- Infection, Inflammation and Cancer Program, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Tim Waterboer
- Infection, Inflammation and Cancer Program, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Lauren R Teras
- Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA
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