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Chen R, Tang Y, Fang S, Gong K, Liu D, Xie Y, Liu G, Tian Y, Zhang L, Li Y, Zhou S. Total, dietary, and supplemental calcium intake and risk of all-cause, cardiovascular, and cancer mortality among U.S. adults: a prospective cohort study from the National Health and Nutrition Examination Survey. Arch Osteoporos 2024; 19:114. [PMID: 39528775 DOI: 10.1007/s11657-024-01457-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2024] [Accepted: 10/01/2024] [Indexed: 11/16/2024]
Abstract
Calcium intake is widely recommended, but its association with mortality remains unclear. This study indicated higher levels of calcium intake were associated with lower mortality in American adults. However, a nonlinear association between calcium intake and mortality suggested that excessive calcium intake beyond a certain threshold may increase mortality risk. PURPOSE The study aimed to investigate the association of total, dietary, or supplemental calcium intake with all-cause, cardiovascular, and cancer mortality in American adults. METHODS This prospective cohort study used the National Health and Nutrition Examination Survey from 2005 to 2018. Participants were categorized into tertiles based on calcium intake. Risks of all-cause, cancer, or cardiovascular mortality and the dose-response relationship were estimated using weighted Cox proportional hazard regression and restricted cubic splines, with adjustments for demographic characteristics, comorbidities, laboratory parameters, and dietary data. RESULTS In total, 6172 participants were included (median age: 61 years), and 869 had died (CVD:217, cancer:224) during a median follow-up of 81 months. After adjusting for confounders, higher total calcium(≥ 1660mg/d) [HR, 95%CI: 0.867 (0.865-0.869)], dietary calcium(≥ 1075mg/d) [HR, 95%CI: 0.711 (0.709-0.713)], and supplemental calcium (≥ 600mg/d) [HR, 95%CI: 0.786 (0.784-0.787)] intake groups were associated with lower all-cause mortality risk compared to the lowest intake group. Similar beneficial associations were found for cardiovascular, cancer mortality, and across subgroups of various ages, genders, races and body mass indexes. In the dose-response analysis, a 'J-shaped' nonlinear relationship was observed between calcium intake and the risk of all-cause, cardiovascular, and cancer mortality. CONCLUSIONS Higher levels of total, dietary, or supplemental calcium were associated with lower all-cause, cardiovascular, or cancer mortality. However, a nonlinear association between calcium intake and mortality suggested that excessive calcium intake beyond a certain threshold may increase mortality risk.
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Affiliation(s)
- Ran Chen
- War Trauma Medical Center, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical Center, Daping Hospital, Army Medical University, Chongqing, 400042, P.R. China
| | - Ying Tang
- War Trauma Medical Center, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical Center, Daping Hospital, Army Medical University, Chongqing, 400042, P.R. China
| | - Shunzheng Fang
- State Key Laboratory of Trauma, Burns and Combined Injury, Department of Rehabilitation Medicine, Daping Hospital, Army Medical University, Chongqing, 400042, P.R. China
| | - Kai Gong
- Department of Orthopaedics, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan Province, 610500, P.R. China
| | - Dong Liu
- War Trauma Medical Center, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical Center, Daping Hospital, Army Medical University, Chongqing, 400042, P.R. China
| | - Yu Xie
- War Trauma Medical Center, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical Center, Daping Hospital, Army Medical University, Chongqing, 400042, P.R. China
| | - Guo Liu
- War Trauma Medical Center, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical Center, Daping Hospital, Army Medical University, Chongqing, 400042, P.R. China
| | - Yu Tian
- Department Of Wound Repair and Rehabilitation Medicine, Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, 400042, P.R. China
- Ministry of Education College of Bioengineering, Chongqing University, Chongqing, 400044, P.R. China
| | - Lianyang Zhang
- War Trauma Medical Center, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical Center, Daping Hospital, Army Medical University, Chongqing, 400042, P.R. China
| | - Yang Li
- War Trauma Medical Center, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical Center, Daping Hospital, Army Medical University, Chongqing, 400042, P.R. China.
| | - Siru Zhou
- War Trauma Medical Center, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical Center, Daping Hospital, Army Medical University, Chongqing, 400042, P.R. China.
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Khan S, Mosvi SN, Vohra S, Poddar NK. Implication of calcium supplementations in health and diseases with special focus on colorectal cancer. Crit Rev Clin Lab Sci 2024; 61:496-509. [PMID: 38456354 DOI: 10.1080/10408363.2024.2322565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 01/31/2024] [Accepted: 02/20/2024] [Indexed: 03/09/2024]
Abstract
Calcium is a fundamental and integrative element and helps to ensure optimal health by regulating various physiological and pathological processes. While there is substantiated evidence confirming the beneficial effects of calcium in the treatment, management, and prevention of various health conditions, including cancer, conflicting studies are imperative to acknowledge the potential negative role of calcium supplementation. The studies on calcium supplementation showed that a specific dose can help in the maintenance of good human health, and in the control of different types of diseases, including cancer. Calcium alone and when combined with vitamin D, emerges as a promising therapeutic option for efficiently managing cancer growth, when used with chemotherapy. Combination therapy is considered a more effective approach for treating advanced types of colorectal cancer. Nevertheless, several challenges drastically influence the treatment of cancer, such as individual discrepancy, drug resistance, and stage of cancer, among others. Henceforth, novel preventive, reliable therapeutic modalities are essential to control and reduce the incidence and mortality of colorectal cancer (CRC). The calcium-sensing receptor (CaSR) plays a pivotal role in calcium homeostasis, metabolism, and regulation of oncogenesis. Numerous studies have underscored the potential of CaSR, a G protein-coupled receptor, as a potential biomarker and target for colorectal cancer prevention and treatment. The multifaceted involvement of CaSR in anti-inflammatory and anti-carcinogenic processes paves the way for its utilization in the diagnosis and management of colorectal cancer. The current review highlights the important role of supplemental calcium in overall health and disease, along with the exploration of intricate mechanisms of CaSR pathways in the management and prevention of colorectal cancer.
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Affiliation(s)
- Shahanavaj Khan
- Department of Medical Lab Technology, Indian Institute of Health and Technology (IIHT), Deoband, Saharanpur, India
- Department of Health Sciences, Novel Global Community Educational Foundation, Sydney, Australia
| | - S Needa Mosvi
- Department of Biosciences, Shri Ram Group of College (SRGC), Muzaffarnagar, India
| | - Saeed Vohra
- Department of Anatomy and Physiology, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia
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Tan S, Ou Y, Yang Y, Huang S, Chen S, Gao Q. Preventive effects of chemical drugs on recurrence of colorectal adenomas: systematic review and Bayesian network meta-analysis. Eur J Gastroenterol Hepatol 2024; 36:62-75. [PMID: 37942763 DOI: 10.1097/meg.0000000000002676] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/10/2023]
Abstract
BACKGROUND The onset of colorectal adenomas (CRAs) is significantly associated with colorectal cancer. The preventive effects of chemical drugs on the recurrence of CRAs have been evaluated in a large number of randomized controlled trials (RCTs). However, there are still uncertainties about the relative effectiveness of such chemical drugs. METHODS We searched relevant RCTs published in six databases up to February 2023. The quality of the included studies was assessed by using the Cochrane risk of bias assessment tool and Review Manager 5.4. Pairwise comparison and network meta-analysis (NMA) were conducted using RStudio to compare the effects of chemical drugs on the recurrence of CRAs. RESULTS Forty-five high-quality RCTs were included. A total of 35 590 (test group: 20 822; control group: 14 768) subjects with a history of CRAs have been enrolled and randomized to receive placebo treatment or one of 24 interventions. Based on surface under the cumulative ranking values and NMA results, difluoromethylornithine (DFMO) + Sulindac significantly reduced the recurrence of CRAs, followed by berberine and nonsteroidal antiinflammatory drugs. CONCLUSION DFMO + Sulindac is more effective in reducing the recurrence of CRAs but has a high risk of adverse events. Considering drug safety, tolerance, and compliance, berberine has a brighter prospect of clinical development. However, further studies are needed to verify our findings.
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Affiliation(s)
- Shufa Tan
- Shaanxi University of Traditional Chinese Medicine, Xianyang
| | - Yan Ou
- Shaanxi University of Traditional Chinese Medicine, Xianyang
| | - Yunyi Yang
- Shanghai University of Traditional Chinese Medicine, Shanghai
| | - Shuilan Huang
- Shaanxi University of Traditional Chinese Medicine, Xianyang
| | - Shikai Chen
- Shaanxi University of Traditional Chinese Medicine, Xianyang
| | - Qiangqiang Gao
- Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine, Xianyang, China
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Sim MG, Teo YN, Teo YH, Syn NL, Li TYW, Yeo LLL, Kong WKF, Tan BYQ, Yip JW, Wong RCC, Poh KK, Yeo TC, Sharma VK, Chai P, Chan MY, Sia CH. Association Between Calcium Supplementation and the Risk of Cardiovascular Disease and Stroke: A Systematic Review and Meta-Analysis. Heart Lung Circ 2023; 32:1230-1239. [PMID: 37743221 DOI: 10.1016/j.hlc.2023.07.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2023] [Revised: 07/12/2023] [Accepted: 07/20/2023] [Indexed: 09/26/2023]
Abstract
BACKGROUND Some observational studies and randomised controlled trials (RCTs) have reported an association between calcium supplementation and increased risk of cardiovascular disease. Previous meta-analyses on the topic, based on data from RCTs and observational studies, have contradictory findings. This meta-analysis was conducted to determine the difference in associated risks of calcium supplementation with cardiovascular disease and stroke in RCTs. METHODS Relevant studies published from database inception to 6 August 2021 were sourced from PubMed, Embase, Scopus, and the Cochrane Central Register of Controlled Trials. Any RCTs focusing on the relationship between calcium supplementation and incidence of cardiovascular disease or stroke were included. Articles were screened independently by two authors, according to the PICO criteria, with disagreements resolved by a third author. RESULTS Twelve RCTs were included in the meta-analysis. Calcium supplementation was not associated with myocardial infarction, total stroke, heart failure admission, and all-cause/cardiovascular mortality. Subgroup analysis focusing on calcium monotherapy/calcium co-therapy with vitamin D, female sex, follow-up duration, and geographical region did not affect the findings. CONCLUSION Calcium supplementation was not associated with myocardial infarction, total stroke, heart failure admission, and cardiovascular/all-cause mortality. Further studies are required to examine and understand these associations.
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Affiliation(s)
- Ming Gin Sim
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Yao Neng Teo
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. http://www.twitter.com/yaoneng_teo
| | - Yao Hao Teo
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Nicholas L Syn
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Tony Y W Li
- Department of Cardiology, National University Heart Centre Singapore, Singapore
| | - Leonard L L Yeo
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Neurology, Department of Medicine, National University Hospital, Singapore
| | - William K F Kong
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Cardiology, National University Heart Centre Singapore, Singapore
| | - Benjamin Y Q Tan
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Neurology, Department of Medicine, National University Hospital, Singapore
| | - James W Yip
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Cardiology, National University Heart Centre Singapore, Singapore
| | - Raymond C C Wong
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Cardiology, National University Heart Centre Singapore, Singapore
| | - Kian Keong Poh
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Cardiology, National University Heart Centre Singapore, Singapore
| | - Tiong-Cheng Yeo
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Cardiology, National University Heart Centre Singapore, Singapore
| | - Vijay Kumar Sharma
- Department of Cardiology, National University Heart Centre Singapore, Singapore; Division of Neurology, Department of Medicine, National University Hospital, Singapore
| | - Ping Chai
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Cardiology, National University Heart Centre Singapore, Singapore
| | - Mark Y Chan
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Cardiology, National University Heart Centre Singapore, Singapore
| | - Ching-Hui Sia
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Cardiology, National University Heart Centre Singapore, Singapore.
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Wi YJ, Na SY. [Calcium, Vitamin D, and Colorectal Cancer]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2023; 82:47-55. [PMID: 37621239 DOI: 10.4166/kjg.2023.091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 08/13/2023] [Accepted: 08/14/2023] [Indexed: 08/26/2023]
Abstract
Colorectal cancer has a high incidence and mortality worldwide, with Westernized lifestyles and diet being significant contributing factors. Vitamin D and calcium have been known to reduce the incidence of colorectal cancer by affecting cell differentiation, proliferation, and apoptosis. Despite observational studies which have suggested that a higher serum vitamin D level can lower the risk of colorectal cancer and improve survival rates, no large-scale randomized controlled trials to establish these benefits have been conducted to date. Calcium intake has also been found to have a beneficial role in reducing the incidence and improving survival rates of colorectal cancer in several observational studies. Moreover, intervention studies have proved its effect in preventing colorectal adenomas. However, there are few intervention studies that have identified the relationship of vitamin D and calcium with colon cancer. To elucidate the impact of vitamin D and calcium supplementation on colorectal cancer, well-designed and large-scale randomized controlled trials are necessary in the future.
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Affiliation(s)
- Young-Jo Wi
- Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Soo-Young Na
- Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Kim SH, Park DH, Lim YJ. Impact of Diet on Colorectal Cancer Progression and Prevention: From Nutrients to Neoplasms. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2023; 82:73-83. [PMID: 37621242 DOI: 10.4166/kjg.2023.079] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 07/20/2023] [Accepted: 07/21/2023] [Indexed: 08/26/2023]
Abstract
Colorectal cancer (CRC), one of the most common cancers worldwide, continues to increase in incidence and mortality rates. This trend is closely linked to changes in dietary habits, which are major risk factors for colorectal cancer. The increase in the incidence of CRC in countries previously considered low-risk and with low socioeconomic status is most likely due to lifestyle and dietary changes. Understanding the influence of dietary factors on the onset of colorectal cancer is essential for prevention and treatment. This review explores the complex interplay between dietary factors and colorectal cancer, focusing on the key nutrients and dietary habits that influence disease onset and progression. The impact of diet on colorectal microbiota and the influence of diet on early-onset colorectal cancer are also reviewed, reviewing recent research on how dietary interventions affect the treatment and recurrence of colorectal cancer. Finally, the future research directions for developing and applying effective dietary intervention strategies are discussed.
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Affiliation(s)
- Sang Hoon Kim
- Department of Internal Medicine, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Korea
| | - Dong Hwan Park
- Department of Internal Medicine, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Korea
| | - Yun Jeong Lim
- Department of Internal Medicine, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Korea
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Lepore Signorile M, Grossi V, Fasano C, Simone C. Colorectal Cancer Chemoprevention: A Dream Coming True? Int J Mol Sci 2023; 24:7597. [PMID: 37108756 PMCID: PMC10140862 DOI: 10.3390/ijms24087597] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 04/17/2023] [Accepted: 04/18/2023] [Indexed: 04/29/2023] Open
Abstract
Colorectal cancer (CRC) is one of the deadliest forms of cancer worldwide. CRC development occurs mainly through the adenoma-carcinoma sequence, which can last decades, giving the opportunity for primary prevention and early detection. CRC prevention involves different approaches, ranging from fecal occult blood testing and colonoscopy screening to chemoprevention. In this review, we discuss the main findings gathered in the field of CRC chemoprevention, focusing on different target populations and on various precancerous lesions that can be used as efficacy evaluation endpoints for chemoprevention. The ideal chemopreventive agent should be well tolerated and easy to administer, with low side effects. Moreover, it should be readily available at a low cost. These properties are crucial because these compounds are meant to be used for a long time in populations with different CRC risk profiles. Several agents have been investigated so far, some of which are currently used in clinical practice. However, further investigation is needed to devise a comprehensive and effective chemoprevention strategy for CRC.
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Affiliation(s)
- Martina Lepore Signorile
- Medical Genetics, National Institute of Gastroenterology—IRCCS “Saverio de Bellis” Research Hospital, Castellana Grotte, 70013 Bari, Italy; (M.L.S.); (C.F.)
| | - Valentina Grossi
- Medical Genetics, National Institute of Gastroenterology—IRCCS “Saverio de Bellis” Research Hospital, Castellana Grotte, 70013 Bari, Italy; (M.L.S.); (C.F.)
| | - Candida Fasano
- Medical Genetics, National Institute of Gastroenterology—IRCCS “Saverio de Bellis” Research Hospital, Castellana Grotte, 70013 Bari, Italy; (M.L.S.); (C.F.)
| | - Cristiano Simone
- Medical Genetics, National Institute of Gastroenterology—IRCCS “Saverio de Bellis” Research Hospital, Castellana Grotte, 70013 Bari, Italy; (M.L.S.); (C.F.)
- Medical Genetics, Department of Precision and Regenerative Medicine and Jonic Area (DiMePRe-J), University of Bari Aldo Moro, 70124 Bari, Italy
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Paul D, Nedelcu AM. The underexplored links between cancer and the internal body climate: Implications for cancer prevention and treatment. Front Oncol 2022; 12:1040034. [PMID: 36620608 PMCID: PMC9815514 DOI: 10.3389/fonc.2022.1040034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Accepted: 11/25/2022] [Indexed: 12/24/2022] Open
Abstract
In order to effectively manage and cure cancer we should move beyond the general view of cancer as a random process of genetic alterations leading to uncontrolled cell proliferation or simply a predictable evolutionary process involving selection for traits that increase cell fitness. In our view, cancer is a systemic disease that involves multiple interactions not only among cells within tumors or between tumors and surrounding tissues but also with the entire organism and its internal "milieu". We define the internal body climate as an emergent property resulting from spatial and temporal interactions among internal components themselves and with the external environment. The body climate itself can either prevent, promote or support cancer initiation and progression (top-down effect; i.e., body climate-induced effects on cancer), as well as be perturbed by cancer (bottom-up effect; i.e., cancer-induced body climate changes) to further favor cancer progression and spread. This positive feedback loop can move the system towards a "cancerized" organism and ultimately results in its demise. In our view, cancer not only affects the entire system; it is a reflection of an imbalance of the entire system. This model provides an integrated framework to study all aspects of cancer as a systemic disease, and also highlights unexplored links that can be altered to both prevent body climate changes that favor cancer initiation, progression and dissemination as well as manipulate or restore the body internal climate to hinder the success of cancer inception, progression and metastasis or improve therapy outcomes. To do so, we need to (i) identify cancer-relevant factors that affect specific climate components, (ii) develop 'body climate biomarkers', (iii) define 'body climate scores', and (iv) develop strategies to prevent climate changes, stop or slow the changes, or even revert the changes (climate restoration).
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Affiliation(s)
- Doru Paul
- Weill Cornell Medicine, New York, NY, United States
| | - Aurora M. Nedelcu
- Biology Department, University of New Brunswick, Fredericton, NB, Canada
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Heer E, Ruan Y, Mah B, Nguyen T, Lyons H, Poirier A, Boyne DJ, O'Sullivan DE, Heitman SJ, Hilsden RJ, Forbes N, Brenner DR. The efficacy of chemopreventive agents on the incidence of colorectal adenomas: A systematic review and network meta-analysis. Prev Med 2022; 162:107169. [PMID: 35878711 DOI: 10.1016/j.ypmed.2022.107169] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Revised: 06/20/2022] [Accepted: 07/17/2022] [Indexed: 10/17/2022]
Abstract
Colorectal cancer (CRC) is the fourth most common cancer and third leading cause of cancer-related death worldwide. Use of chemopreventive agents (CPAs) to reduce the incidence of precursor colorectal adenomas could lower the future burden of CRC. Many classes of potential CPAs have been investigated. To identify the most effective CPAs, we conducted a systematic review and a network meta-analysis (NMA). An electronic search was performed through August 2020 to identify all randomized controlled trials (RCTs) assessing the efficacy of CPAs in reducing the incidence of colorectal adenomas at the time of surveillance colonoscopy among patients who had previously undergone polypectomy during an index colonoscopy. In total, 33 RCTs were included in the NMA, which was conducted under a Bayesian inference framework. Random effects models were used with adjustment for follow-up length and control group event rates to yield relative risks (RRs) and 95% credible intervals (CrIs). Our full network consisted of 13 interventions in addition to a placebo arm. Of 20,925 included patients, 7766 had an adenoma. Compared to placebo, the combination of difluoromethylornithine (DFMO) + Sulindac (RR 0.24, CrI 0.10-0.55) demonstrated a protective effect, while aspirin had a RR of 0.77 (CrI 0.60-1.00), celecoxib 800 mg had a RR of 0.56 (CrI 0.31-1.01) and metformin had a RR of 0.56 (CrI 0.22-1.39). Our results suggest that select CPAs may be efficacious in preventing the development of adenomas. Further studies are needed to identify those patients most likely to benefit and the minimum effective dosages of CPAs.
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Affiliation(s)
- Emily Heer
- Forzani & MacPhail Colon Cancer Screening Centre, University of Calgary, Calgary, AB, Canada
| | - Yibing Ruan
- Forzani & MacPhail Colon Cancer Screening Centre, University of Calgary, Calgary, AB, Canada; Department of Cancer Epidemiology and Prevention Research, Cancer Control Alberta, Alberta Health Services, Calgary, AB, Canada
| | - Brittany Mah
- Forzani & MacPhail Colon Cancer Screening Centre, University of Calgary, Calgary, AB, Canada
| | - Teresa Nguyen
- Forzani & MacPhail Colon Cancer Screening Centre, University of Calgary, Calgary, AB, Canada
| | - Hannah Lyons
- Forzani & MacPhail Colon Cancer Screening Centre, University of Calgary, Calgary, AB, Canada
| | - Abbey Poirier
- Forzani & MacPhail Colon Cancer Screening Centre, University of Calgary, Calgary, AB, Canada; Department of Cancer Epidemiology and Prevention Research, Cancer Control Alberta, Alberta Health Services, Calgary, AB, Canada
| | - Devon J Boyne
- Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Dylan E O'Sullivan
- Forzani & MacPhail Colon Cancer Screening Centre, University of Calgary, Calgary, AB, Canada; Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Steven J Heitman
- Forzani & MacPhail Colon Cancer Screening Centre, University of Calgary, Calgary, AB, Canada; Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Robert J Hilsden
- Forzani & MacPhail Colon Cancer Screening Centre, University of Calgary, Calgary, AB, Canada; Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Nauzer Forbes
- Forzani & MacPhail Colon Cancer Screening Centre, University of Calgary, Calgary, AB, Canada; Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Darren R Brenner
- Forzani & MacPhail Colon Cancer Screening Centre, University of Calgary, Calgary, AB, Canada; Department of Cancer Epidemiology and Prevention Research, Cancer Control Alberta, Alberta Health Services, Calgary, AB, Canada; Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
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Laser Ablation ICP-MS Analysis of Chemically Different Regions of Rat Prostate Gland with Implanted Cancer Cells. APPLIED SCIENCES-BASEL 2022. [DOI: 10.3390/app12031474] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
The comparison of tissues analyzed by LA-ICP-MS is challenging in many aspects, both medical and mathematical. The concept of distinguishing regions of interest (ROIs) was proposed in the literature, allowing for data reduction and targeted comparative analysis. ROIs can be drawn before any analysis, by indicating the anatomical parts of tissue, or after the first step of analysis, by using elemental distribution maps and characteristic regions of enrichment in selected elements. A simple method for identifying different regions, without the manual extraction of image fragments, is highly needed in biological experiments, where large groups of individuals (with samples taken from each of them) is very common. In the present study, two ROIs were distinguished: (1) tissue-rich in fat (and tissue-poor in water); and (2) tissue-rich in water (and tissue-poor in fat). ROIs were extracted mathematically, using an algorithm based on the relationship between 13C and 23Na signal intensities. A cut-off point was indicated in the point of the simultaneous decrease in 13C and increase in 23Na signal intensity. Separate analyses of chemically different ROIs allow for targeted comparison, which is a great advantage of laser ablation over liquid introductions to ICP-MS. In the present experiment, tissues were provided from animals with implanted prostate cancer cells as well as supplemented with mineral compounds particularly important both for prostate gland functions (Zn and Se) and neoplastic processes (Ca, Fe, and Cu). One of the goals was to try to determine whether dietary supplementation qualitatively and quantitatively affects the mineral composition of the prostate gland.
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MEI LUO XUE, KHAN SHAHANAVAJ, MALIK ABDUL, M. ALDAKHEEL FAHAD, AHMAD CHAUDHARY ANIS, BAZARBASHI SHOUKI, TABATABAIE FATEMEH. Calcium supplementation in colorectal cancer prevention: A systematic meta-analysis of adverse events. BIOCELL 2022; 46:759-767. [DOI: 10.32604/biocell.2022.016586] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2021] [Accepted: 05/20/2021] [Indexed: 02/05/2023]
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Johnstone MS, Lynch G, Park J, McSorley S, Edwards J. Novel Methods of Risk Stratifying Patients for Metachronous, Pre-Malignant Colorectal Polyps: A Systematic Review. Crit Rev Oncol Hematol 2021; 164:103421. [PMID: 34246774 DOI: 10.1016/j.critrevonc.2021.103421] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 06/29/2021] [Accepted: 06/29/2021] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION Despite conventional measures of future polyp risk (histology, dysplasia, size, number), surveillance places a burden on patients and colonoscopy services. We aimed to review novel risk stratification techniques. METHODS A systematic literature review was performed for studies using genomics, transcriptomics, IHC or microbiome as markers of metachronous polyp risk. RESULTS 4165 papers underwent title, 303 abstract and 215 full paper review. 25 papers were included. 49 mutations/ SNPs/ haplotypes in 23 genes/ chromosomal regions (KRAS, APC, EGFR, COX1/2, IL23R, DRD2, CYP2C9/24A1/7A1, UGT1A6, ODC, ALOX12/15, PGDH, SRC, IGSF5, KCNS3, EPHB1/ KY, FAM188b, 3p24.1, 9q33.2, 13q33.2) correlated with metachronous adenoma / advanced adenoma risk. Expression levels of 6 proteins correlated with metachronous adenoma (p53, β-catenin, COX2, Adnab-9, ALDH1A1) or sessile serrated polyp (ANXA10) risk. CONCLUSION Although genomic and IHC markers correlated with metachronous polyp risk, it seems likely that a panel of novel markers will be required to refine this risk.
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Affiliation(s)
- Mark S Johnstone
- Academic Unit of Surgery, School of Medicine, University of Glasgow, United Kingdom.
| | - Gerard Lynch
- Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, United Kingdom
| | - James Park
- Academic Unit of Surgery, School of Medicine, University of Glasgow, United Kingdom
| | - Stephen McSorley
- Academic Unit of Surgery, School of Medicine, University of Glasgow, United Kingdom
| | - Joanne Edwards
- Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, United Kingdom
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Tsilidis KK, Papadimitriou N, Dimou N, Gill D, Lewis SJ, Martin RM, Murphy N, Markozannes G, Zuber V, Cross AJ, Burrows K, Lopez DS, Key TJ, Travis RC, Perez-Cornago A, Hunter DJ, van Duijnhoven FJB, Albanes D, Arndt V, Berndt SI, Bézieau S, Bishop DT, Boehm J, Brenner H, Burnett-Hartman A, Campbell PT, Casey G, Castellví-Bel S, Chan AT, Chang-Claude J, de la Chapelle A, Figueiredo JC, Gallinger SJ, Giles GG, Goodman PJ, Gsur A, Hampe J, Hampel H, Hoffmeister M, Jenkins MA, Keku TO, Kweon SS, Larsson SC, Le Marchand L, Li CI, Li L, Lindblom A, Martín V, Milne RL, Moreno V, Nan H, Nassir R, Newcomb PA, Offit K, Pharoah PDP, Platz EA, Potter JD, Qi L, Rennert G, Sakoda LC, Schafmayer C, Slattery ML, Snetselaar L, Schenk J, Thibodeau SN, Ulrich CM, Van Guelpen B, Harlid S, Visvanathan K, Vodickova L, Wang H, White E, Wolk A, Woods MO, Wu AH, Zheng W, Bueno-de-Mesquita B, Boutron-Ruault MC, Hughes DJ, Jakszyn P, Kühn T, Palli D, Riboli E, Giovannucci EL, Banbury BL, Gruber SB, Peters U, Gunter MJ. Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent: a Mendelian randomization study. Am J Clin Nutr 2021; 113:1490-1502. [PMID: 33740060 PMCID: PMC8168352 DOI: 10.1093/ajcn/nqab003] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 01/04/2021] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited. OBJECTIVES To complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR). METHODS Two-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions. RESULTS Nominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer [ORs per SD (ORSD): 1.08; 95% CI: 1.00, 1.17; P value = 0.05] and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12; 95% CI: 1.03, 1.21; P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98; 95% CI: 0.96, 1.00; P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of β-carotene, calcium, copper, folate, magnesium, phosphorus, and vitamin B-6 were not associated with disease risk. CONCLUSIONS These results suggest possible causal associations of circulating iron and vitamin B-12 (positively) and selenium (inversely) with risk of colon cancer.
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Affiliation(s)
- Konstantinos K Tsilidis
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
| | - Nikos Papadimitriou
- Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France
| | - Niki Dimou
- Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France
| | - Dipender Gill
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
| | - Sarah J Lewis
- Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
- Medical Research Council Integrative Epidemiology Unit, Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
| | - Richard M Martin
- Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
- Medical Research Council Integrative Epidemiology Unit, Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
- University Hospitals Bristol National Health Service Foundation Trust National Institute for Health Research Bristol Biomedical Research Centre, University of Bristol, Bristol, United Kingdom
| | - Neil Murphy
- Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France
| | - Georgios Markozannes
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
| | - Verena Zuber
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
- Medical Research Council Biostatistics Unit, School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom
| | - Amanda J Cross
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
| | - Kimberley Burrows
- Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
- Medical Research Council Integrative Epidemiology Unit, Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
| | - David S Lopez
- Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, Galveston, TX, USA
| | - Timothy J Key
- Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
| | - Ruth C Travis
- Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
| | - Aurora Perez-Cornago
- Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
| | - David J Hunter
- Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
| | | | - Demetrius Albanes
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA
| | - Volker Arndt
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Sonja I Berndt
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA
| | - Stéphane Bézieau
- Medical Genetics Service, University Hospital Center (CHU) Nantes, Nantes, France
| | - D Timothy Bishop
- , Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, United Kingdom
| | - Juergen Boehm
- Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA
- Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
| | | | - Peter T Campbell
- Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA, USA
| | - Graham Casey
- Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA
| | - Sergi Castellví-Bel
- Gastroenterology Department, Hospital Clinic, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Biomedical Research Network Center for Liver and Digestive Diseases (CIBEREHD), University of Barcelona, Barcelona, Spain
| | - Andrew T Chan
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Broad Institute of Harvard and MIT, Cambridge, MA, USA
- Department of Epidemiology, Harvard TH Chan School of Public Health, Harvard University, Boston, MA, USA
- Department of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Harvard University, Boston, MA, USA
| | - Jenny Chang-Claude
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
- University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg, Hamburg, Germany
| | - Albert de la Chapelle
- Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH, USA
- Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
| | - Jane C Figueiredo
- Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Steven J Gallinger
- Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Graham G Giles
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia
- Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia
| | - Phyllis J Goodman
- SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Andrea Gsur
- Institute of Cancer Research, Department of Medicine I, Medical University Vienna, Vienna, Austria
| | - Jochen Hampe
- Department of Medicine I, University Hospital Dresden, Dresden University of Technology (TU Dresden), Dresden, Germany
| | - Heather Hampel
- Division of Human Genetics, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA
| | - Michael Hoffmeister
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Mark A Jenkins
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia
| | - Temitope O Keku
- Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA
| | - Sun-Seog Kweon
- Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea
- Jeonnam Regional Cancer Center, Chonnam National University Hwasun Hospital, Hwasun, Republic of Korea
| | - Susanna C Larsson
- Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden
| | | | - Christopher I Li
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Li Li
- Department of Family Medicine, University of Virginia, Charlottesville, VA, USA
| | - Annika Lindblom
- Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden
- Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden
| | - Vicente Martín
- CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain
- Biomedicine Institute (IBIOMED), University of León, León, Spain
| | - Roger L Milne
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia
- Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia
| | - Victor Moreno
- CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain
- Oncology Data Analytics Program, Catalan Institute of Oncology-Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
- Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain
- ONCOBEL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
| | - Hongmei Nan
- Department of Epidemiology, Richard M Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA
- IU Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN, USA
| | - Rami Nassir
- Department of Pathology, School of Medicine, Umm Al-Qura'a University, Mecca, Saudi Arabia
| | - Polly A Newcomb
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- School of Public Health, University of Washington, Seattle, WA, USA
| | - Kenneth Offit
- Clinical Genetics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
- Department of Medicine, Weill Cornell Medical College, New York, NY, USA
| | - Paul D P Pharoah
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
| | - Elizabeth A Platz
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - John D Potter
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Centre for Public Health Research, Massey University, Wellington, New Zealand
| | - Lihong Qi
- Department of Public Health Sciences, School of Medicine, University of California Davis, Davis, CA, USA
| | - Gad Rennert
- Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel
- Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
- Clalit National Cancer Control Center, Haifa, Israel
| | - Lori C Sakoda
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA
| | - Clemens Schafmayer
- Department of General Surgery, University Hospital Rostock, Rostock, Germany
| | - Martha L Slattery
- Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA
| | - Linda Snetselaar
- Department of Epidemiology, University of Iowa College of Public Health, Iowa City, IA, USA
| | - Jeanette Schenk
- SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Stephen N Thibodeau
- Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | - Cornelia M Ulrich
- Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA
- Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA
| | - Bethany Van Guelpen
- Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden
| | - Sophia Harlid
- Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden
| | - Kala Visvanathan
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Ludmila Vodickova
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic
- Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic
- Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic
| | - Hansong Wang
- University of Hawaii Cancer Center, Honolulu, HI, USA
| | - Emily White
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Department of Epidemiology, University of Washington, Seattle, WA, USA
| | - Alicja Wolk
- Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden
| | - Michael O Woods
- Discipline of Genetics, Memorial University of Newfoundland, St. John's, Newfoundland, Canada
| | - Anna H Wu
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Wei Zheng
- Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Bas Bueno-de-Mesquita
- Formerly, Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands
| | - Marie-Christine Boutron-Ruault
- Faculty of Medicine, CESP, University of Paris-Sud, Faculty of Medicine UVSQ, INSERM, University of Paris-Saclay, Villejuif, France
- Centre for Research in Epidemiology and Population Health (CESP), Gustave Roussy, Villejuif, France
| | - David J Hughes
- Cancer Biology and Therapeutics Group, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland
| | - Paula Jakszyn
- Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology- Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
- Blanquerna Faculty of Health Sciences, Ramon Llull University, Barcelona, Spain
| | - Tilman Kühn
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Domenico Palli
- Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network-ISPRO, Florence, Italy
| | - Elio Riboli
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
| | - Edward L Giovannucci
- Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Department of Epidemiology, Harvard TH Chan School of Public Health, Harvard University, Boston, MA, USA
- Department of Nutrition, Harvard TH Chan School of Public Health, Harvard University, Boston, MA, USA
| | - Barbara L Banbury
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Stephen B Gruber
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
- USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA
| | - Ulrike Peters
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Department of Epidemiology, University of Washington, Seattle, WA, USA
| | - Marc J Gunter
- Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France
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Emami MH, Salehi M, Hassanzadeh Keshteli A, Mansourian M, Mohammadzadeh S, Maghool F. Calcium and dairy products in the chemoprevention of colorectal adenomas: a systematic review and meta-analysis. Crit Rev Food Sci Nutr 2021; 62:7168-7183. [PMID: 33951958 DOI: 10.1080/10408398.2021.1911927] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
The risk of transition to colorectal cancer (CRC) in advanced colorectal adenomas (ACAs) is about 2.5 times higher than the non-advanced ones. This systematic review and meta-analysis was performed to determine the effect of calcium and dairy products on the incidence of CAs and ACAs. Six databases were systematically searched and 37 relevant clinical trials and observational studies involving over 10,964 cases were selected for inclusion. The results showed that calcium consumption reduced the risk of CAs incidence by 8% (RR: 0.92; 95% CI: 0.89-0.96), and calcium intake as a food and dairy product reduced it about 21% (RR: 0.79; 95% CI: 0.72-0.86), and 12% (RR: 0.88; 95% CI: 0.78-0.98), respectively. However, calcium supplementation did not show a significant effect on CAs incidence (RR: 0.97; 95% CI: 0.89-1.05). Results also revealed that total calcium intake markedly reduced the risk of ACAs (RR: 0.79; 95% CI: 0.73-0.85) and the risk of recurrence of adenomas about 12% (RR: 0.88; 95% CI: 0.84-0.93). Our results suggest that natural sources of calcium such as dairy products and foods may have more effective role than supplementary calcium in terms of reducing the risk of incidence and recurrence of colorectal adenomas and advanced adenomas.
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Affiliation(s)
- Mohammad Hassan Emami
- Poursina Hakim Digestive Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mansoor Salehi
- Cellular Molecular and Genetics Research Center, Isfahan University of Medical Science, Isfahan, Iran
| | | | - Marjan Mansourian
- Department of Epidemiology and Biostatistics, School of Health, Isfahan University of Medical Science, Isfahan, Iran
| | - Samane Mohammadzadeh
- Poursina Hakim Digestive Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Fatemeh Maghool
- Poursina Hakim Digestive Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
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Veettil SK, Kew ST, Lim KG, Phisalprapa P, Kumar S, Lee YY, Chaiyakunapruk N. Very-low-dose aspirin and surveillance colonoscopy is cost-effective in secondary prevention of colorectal cancer in individuals with advanced adenomas: network meta-analysis and cost-effectiveness analysis. BMC Gastroenterol 2021; 21:130. [PMID: 33743605 PMCID: PMC7981989 DOI: 10.1186/s12876-021-01715-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Accepted: 03/10/2021] [Indexed: 02/20/2023] Open
Abstract
BACKGROUND Individuals with advanced colorectal adenomas (ACAs) are at high risk for colorectal cancer (CRC), and it is unclear which chemopreventive agent (CPA) is safe and cost-effective for secondary prevention. We aimed to determine, firstly, the most suitable CPA using network meta-analysis (NMA) and secondly, cost-effectiveness of CPA with or without surveillance colonoscopy (SC). METHODS Systematic review and NMA of randomised controlled trials were performed, and the most suitable CPA was chosen based on efficacy and the most favourable risk-benefit profile. The economic benefits of CPA alone, 3 yearly SC alone, and a combination of CPA and SC were determined using the cost-effectiveness analysis (CEA) in the Malaysian health-care perspective. Outcomes were reported as incremental cost-effectiveness ratios (ICERs) in 2018 US Dollars ($) per quality-adjusted life-year (QALY), and life-years (LYs) gained. RESULTS According to NMA, the risk-benefit profile favours the use of aspirin at very-low-dose (ASAVLD, ≤ 100 mg/day) for secondary prevention in individuals with previous ACAs. Celecoxib is the most effective CPA but the cardiovascular adverse events are of concern. According to CEA, the combination strategy (ASAVLD with 3-yearly SC) was cost-saving and dominates its competitors as the best buy option. The probability of being cost-effective for ASAVLD alone, 3-yearly SC alone, and combination strategy were 22%, 26%, and 53%, respectively. Extending the SC interval to five years in combination strategy was more cost-effective when compared to 3-yearly SC alone (ICER of $484/LY gain and $1875/QALY). However, extending to ten years in combination strategy was not cost-effective. CONCLUSION ASAVLD combined with 3-yearly SC in individuals with ACAs may be a cost-effective strategy for CRC prevention. An extension of SC intervals to five years can be considered in resource-limited countries.
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Affiliation(s)
- Sajesh K Veettil
- Department of Pharmacotherapy, College of Pharmacy, The University of Utah, 30 2000 E, Salt Lake City, UT, 84112, USA.,Department of Pharmacy Practice, School of Pharmacy, International Medical University, Bukit Jalil, 57000, Kuala Lumpur, Malaysia
| | - Siang Tong Kew
- Department of Internal Medicine, School of Medicine, International Medical University, International Medical University, Bukit Jalil, 57000, Kuala Lumpur, Malaysia
| | - Kean Ghee Lim
- Department of Surgery, International Medical University, Negeri Sembilan, Jalan Rasah, 70300, Seremban, Malaysia
| | - Pochamana Phisalprapa
- Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand
| | - Suresh Kumar
- Department of Pharmacy Practice, School of Pharmacy, International Medical University, Bukit Jalil, 57000, Kuala Lumpur, Malaysia
| | - Yeong Yeh Lee
- School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia.,Gut Research Group, Faculty of Medicine, National University of Malaysia, Kuala Lumpur, Malaysia
| | - Nathorn Chaiyakunapruk
- Department of Pharmacotherapy, College of Pharmacy, The University of Utah, 30 2000 E, Salt Lake City, UT, 84112, USA. .,School of Pharmacy, Monash University Malaysia, Bandar Sunway, 47500, Subang Jaya, Selangor, Malaysia.
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Zhou E, Rifkin S. Colorectal Cancer and Diet: Risk Versus Prevention, Is Diet an Intervention? Gastroenterol Clin North Am 2021; 50:101-111. [PMID: 33518157 DOI: 10.1016/j.gtc.2020.10.012] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Colorectal cancer is the third most common cause of cancer in men and women in the world. Epidemiologic research approximates that half of colon cancer risk is preventable by modifiable risk factors, including diet. This article reviews prior studies involving certain food items and their relation to colorectal cancer, to elucidate whether diet can be a potential intervention.
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Affiliation(s)
- Elinor Zhou
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 431, Baltimore, MD, USA.
| | - Samara Rifkin
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Michigan School of Medicine, 1150 West Medical Center Drive, 6520 MSRB1, Ann Arbor, MI, USA
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17
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Myung SK, Kim HB, Lee YJ, Choi YJ, Oh SW. Calcium Supplements and Risk of Cardiovascular Disease: A Meta-Analysis of Clinical Trials. Nutrients 2021; 13:nu13020368. [PMID: 33530332 PMCID: PMC7910980 DOI: 10.3390/nu13020368] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 01/20/2021] [Accepted: 01/21/2021] [Indexed: 01/27/2023] Open
Abstract
Background: Recent systematic reviews and meta-analyses of randomized, double-blind, placebo-controlled trials (double-blind, placebo-controlled RCTs) have reported controversial findings regarding the associations between calcium supplements on the risk of cardiovascular disease (CVD). This meta-analysis aimed to investigate the association between them. Methods: We searched PubMed, EMBASE, the Cochrane Library, and the bibliographies of relevant articles for double-blind, placebo-controlled RCTs in November, 2020. Relative risks (RRs) with 95% confidence intervals (CIs) for the risk of cardiovascular disease were calculated using a random effects model. The main outcomes were CVD, coronary heart disease (CHD), and cerebrovascular disease. Results: A total of 13 double-blind, placebo-controlled RCTs (n = 28,935 participants in an intervention group and 14,243 in a control group)) were included in the final analysis. Calcium supplements significantly increased the risk of CVD (RR 1.15, 95% CI 1.06–1.25], I2 = 0.0%, n = 14) and CHD (RR 1.16, 95% CI 1.05–1.28], I2 = 0.0%, n = 9) in double-blind, placebo-controlled RCTs, specifically in healthy postmenopausal women. In the subgroup meta-analysis, dietary calcium intake of 700–1000 mg per day or supplementary calcium intake of 1000 mg per day significantly increased the risk of CVD and CHD. Conclusions: The current meta-analysis found that calcium supplements increased a risk of CVD by about 15% in healthy postmenopausal women.
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Affiliation(s)
- Seung-Kwon Myung
- Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, Goyang 10408, Korea
- Cancer Epidemiology Branch, Division of Cancer Epidemiology and Prevention, Research Institute, National Cancer Center, Goyang 10408, Korea
- Department of Family Medicine and Center for Cancer Prevention and Detection, Hospital, National Cancer Center, Goyang 10408, Korea
- Correspondence:
| | - Hong-Bae Kim
- Department of Family Medicine, MyongJi Hospital, Hanyang University College of Medicine, Goyang 10475, Korea;
| | - Yong-Jae Lee
- Department of Family Medicine, College of Medicine, Yonsei University, Seoul 03722, Korea;
| | - Yoon-Jung Choi
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul 03080, Korea;
| | - Seung-Won Oh
- Department of Family Medicine, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul 06236, Korea;
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Skrajnowska D, Jagielska A, Ruszczyńska A, Wagner B, Bielecki W, Bobrowska-Korczak B. Title Changes in the Mineral Composition of Rat Femoral Bones Induced by Implantation of LNCaP Prostate Cancer Cells and Dietary Supplementation. Nutrients 2020; 13:E100. [PMID: 33396969 PMCID: PMC7823861 DOI: 10.3390/nu13010100] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 12/26/2020] [Accepted: 12/27/2020] [Indexed: 11/16/2022] Open
Abstract
Prostate cancer (PCa) is the second most frequent cancer in men and the fifth most common cause of death worldwide, with an estimated 378,553 deaths in 2020. Prostate cancer shows a strong tendency to form metastatic foci in the bones. A number of interactions between cancer cells attacking bones and cells of the bone matrix lead to destruction of the bone and growth of the tumour. The last few decades have seen increased interest in the precise role of minerals in human health and disease. Tumour cells accumulate various minerals that promote their intensive growth. Bone, as a storehouse of elements, can be a valuable source of them for the growing tumour. There are also reports suggesting that the presence of some tumours, e.g., of the breast, can adversely affect bone structure even in the absence of metastasis to this organ. This paper presents the effect of chronic dietary intake of calcium, iron and zinc, administered in doses corresponding maximally to twice their level in a standard diet, on homeostasis of selected elements (Ca, K, Zn, Fe, Cu, Sr, Ni, Co, Mn and Mo) in the femoral bones of healthy rats and rats with implanted cancer cells of the LNCaP line. The experiment was conducted over 90 days. After the adaptation period, the animals were randomly divided into four dietary groups: standard diet and supplementation with Zn, Fe and Ca. Every dietary group was divided into experimental group (with implanted cancer cells) and control group (without implanted cancer cells). The cancer cells (LnCaP) were implanted intraperitoneally in the amount 1 × 106 to the rats at day 90 of their lifetime. Bone tissue was dried and treated with microwave-assisted mineral digestation. Total elemental content was quantified by ICP-MS. Student's t-test and Anova or Kruskal-Wallis tests were applied in order to compare treatment and dietary groups. In the case of most of the diets, especially the standard diet, the femoral bones of rats with implanted LNCaP cells showed a clear downward trend in the content of the elements tested, which may be indicative of slow osteolysis taking place in the bone tissue. In the group of rats receiving the standard diet, there were significant reductions in the content of Mo (by 83%), Ca (25%), Co (22%), Mn (13%), K (13%) and Sr (9%) in the bone tissue of rats with implanted LNCaP cells in comparison with the control group receiving the same diet but without LNCaP implantation. Supplementation of the rat diet with calcium, zinc and iron decreased the frequency of these changes relative to the standard diet, which may indicate that the diet had an inhibitory effect on bone resorption in conditions of LNCaP implantation. The principal component analysis (PCA) score plot confirms the pronounced effect of implanted LNCaP cells and the standard diet on bone composition. At the same time, supplementation with calcium, zinc and iron seems to improve bone composition. The microelements that most often underwent quantitative changes in the experimental conditions were cobalt, manganese and molybdenum.
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Affiliation(s)
- Dorota Skrajnowska
- Faculty of Pharmacy with the Laboratory Medicine Division, Department of Bromatology, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland;
| | - Agata Jagielska
- Biological and Chemical Research Centre, Faculty of Chemistry, University of Warsaw, Zwirki i Wigury 101, 02-089 Warsaw, Poland; (A.J.); (A.R.); (B.W.)
| | - Anna Ruszczyńska
- Biological and Chemical Research Centre, Faculty of Chemistry, University of Warsaw, Zwirki i Wigury 101, 02-089 Warsaw, Poland; (A.J.); (A.R.); (B.W.)
| | - Barbara Wagner
- Biological and Chemical Research Centre, Faculty of Chemistry, University of Warsaw, Zwirki i Wigury 101, 02-089 Warsaw, Poland; (A.J.); (A.R.); (B.W.)
| | - Wojciech Bielecki
- Department of Pathology and Veterinary Diagnostics, Faculty of Veterinary Medicine, Warsaw University of Live Sciences, Nowoursynowska 159c, 02-787 Warsaw, Poland;
| | - Barbara Bobrowska-Korczak
- Faculty of Pharmacy with the Laboratory Medicine Division, Department of Bromatology, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland;
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19
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Galan-Ros J, Ramos-Arenas V, Conesa-Zamora P. Predictive values of colon microbiota in the treatment response to colorectal cancer. Pharmacogenomics 2020; 21:1045-1059. [PMID: 32896201 DOI: 10.2217/pgs-2020-0044] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
The crosstalk between the colon mucosa and the microbiota represents a complex and delicate equilibrium. Gastrointestinal diseases such as inflammatory bowel disease and colorectal cancer (CRC) are associated with a state of altered microbiota composition known as dysbiosis, which seems to play a causative role in some of these illnesses. Recent reports have shown that the colorectal microbiome is responsible for the response and safety to treatments against CRC, especially immunotherapy, hence opening the possibility to use bacteria as a predictive marker and also as a therapeutic agent. The review objective is to summarize updated reports about the the implication of the colorectal microbiome in the development of CRC, in treatment response and its potential as a therapeutic approach.
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Affiliation(s)
- Jorge Galan-Ros
- Microbiology Department, Santa Lucia University Hospital (HGUSL), Cartagena, 30202, Spain
| | - Verónica Ramos-Arenas
- Clinical Analysis Department, Santa Lucia University Hospital (HGUSL), Cartagena, 30202, Spain
| | - Pablo Conesa-Zamora
- Clinical Analysis Department, Santa Lucia University Hospital (HGUSL), Cartagena, 30202, Spain.,Department of Histology & Pathology, Faculty of Life Sciences, Universidad Católica de Murcia (UCAM), Murcia, 30107, Spain.,Research Group on Molecular Pathology & Pharmacogenetics, Institute for Biomedical Research of Murcia (IMIB), Calle Mezquita sn, Cartagena, 30202, Spain
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20
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Rock CL, Thomson C, Gansler T, Gapstur SM, McCullough ML, Patel AV, Andrews KS, Bandera EV, Spees CK, Robien K, Hartman S, Sullivan K, Grant BL, Hamilton KK, Kushi LH, Caan BJ, Kibbe D, Black JD, Wiedt TL, McMahon C, Sloan K, Doyle C. American Cancer Society guideline for diet and physical activity for cancer prevention. CA Cancer J Clin 2020; 70:245-271. [PMID: 32515498 DOI: 10.3322/caac.21591] [Citation(s) in RCA: 396] [Impact Index Per Article: 79.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 10/21/2019] [Accepted: 10/21/2019] [Indexed: 12/14/2022] Open
Abstract
The American Cancer Society (ACS) publishes the Diet and Physical Activity Guideline to serve as a foundation for its communication, policy, and community strategies and, ultimately, to affect dietary and physical activity patterns among Americans. This guideline is developed by a national panel of experts in cancer research, prevention, epidemiology, public health, and policy, and reflects the most current scientific evidence related to dietary and activity patterns and cancer risk. The ACS guideline focuses on recommendations for individual choices regarding diet and physical activity patterns, but those choices occur within a community context that either facilitates or creates barriers to healthy behaviors. Therefore, this committee presents recommendations for community action to accompany the 4 recommendations for individual choices to reduce cancer risk. These recommendations for community action recognize that a supportive social and physical environment is indispensable if individuals at all levels of society are to have genuine opportunities to choose healthy behaviors. This 2020 ACS guideline is consistent with guidelines from the American Heart Association and the American Diabetes Association for the prevention of coronary heart disease and diabetes as well as for general health promotion, as defined by the 2015 to 2020 Dietary Guidelines for Americans and the 2018 Physical Activity Guidelines for Americans.
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Affiliation(s)
- Cheryl L Rock
- Department of Family Medicine and Public Health, School of Medicine, University of California at San Diego, San Diego, California
| | - Cynthia Thomson
- Health Promotion Sciences, Mel & Enid Zuckerman College of Public Health Distinguished Outreach Faculty, University of Arizona, Tucson, Arizona
| | - Ted Gansler
- Intramural Research, American Cancer Society, Atlanta, Georgia
| | - Susan M Gapstur
- Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia
| | - Marjorie L McCullough
- Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia
| | - Alpa V Patel
- Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia
| | | | - Elisa V Bandera
- Cancer Epidemiology and Health Outcomes, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey
| | - Colleen K Spees
- Division of Medical Dietetics and Health Sciences, School of Health and Rehabilitation Sciences, Comprehensive Cancer Center and James Solove Research Institute, The Ohio State University College of Medicine, Columbus, Ohio
| | - Kimberly Robien
- Department of Exercise and Nutrition Sciences, Department of Epidemiology, Milken Institute School of Public Health, George Washington University, Washington, DC
| | - Sheri Hartman
- Department of Family Medicine and Public Health, University of San Diego Moores Cancer Center, La Jolla, California
| | | | - Barbara L Grant
- Saint Alohonsus Regional Medical Center Cancer Care Center, Boise, Idaho
| | - Kathryn K Hamilton
- Carol G. Simon Cancer Center, Morristown Memorial Hospital, Morristown, New Jersey
| | - Lawrence H Kushi
- Division of Research, Kaiser Permanente Northern California, Oakland, California
| | - Bette J Caan
- Division of Research, Kaiser Permanente Northern California, Oakland, California
| | - Debra Kibbe
- Georgia Health Policy Center, Andrew Young School of Policy Studies, Georgia State University, Atlanta, Georgia
| | - Jessica Donze Black
- Community Health, American Heart Association/American Stroke Association, Washington, DC
| | - Tracy L Wiedt
- Cancer Control, American Cancer Society, Atlanta, Georgia
| | - Catherine McMahon
- Strategy and Operations, American Cancer Society Cancer Action Network, Washington, DC
| | - Kirsten Sloan
- Strategy and Operations, American Cancer Society Cancer Action Network, Washington, DC
| | - Colleen Doyle
- Cancer Control, American Cancer Society, Atlanta, Georgia
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21
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Ingles DP, Cruz Rodriguez JB, Garcia H. Supplemental Vitamins and Minerals for Cardiovascular Disease Prevention and Treatment. Curr Cardiol Rep 2020; 22:22. [PMID: 32067177 DOI: 10.1007/s11886-020-1270-1] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE OF REVIEW The objective of this study is to explore the current literature supporting the use oral multivitamins and multi/minerals (OMVMs) for cardiovascular diseases (CVD) treatment and prevention. RECENT FINDINGS Data on multivitamins, vitamin C and D, coenzyme Q, calcium, and selenium, has showed no consistent benefit for the prevention of CVD, myocardial infarction, or stroke, nor was there a benefit for all-cause mortality to support their routine supplementation. Folic acid alone and B vitamins with folic acid, B6 and B12, reduce stroke, whereas niacin and antioxidants are associated with an increased risk of all-cause mortality. Iron deficiency should be avoided and treated if found, but routine supplementation to those without deficiency is not evidence based. Despite the high supplement use by the general public, there is no evidence to support the routine supplementation of oral multivitamins and multi/minerals (OVMN) for CVD prevention or treatment.
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Affiliation(s)
- David Perez Ingles
- Department of Internal Medicine, Texas Tech University Health Sciences Center El Paso, 4800 Alberta Avenue, El Paso, TX, 79905, USA.
| | - Jose B Cruz Rodriguez
- Department of Internal Medicine, Division of Cardiovascular Diseases, Texas Tech University Health Sciences Center, El Paso, TX, USA
| | - Hernando Garcia
- Division of Pulmonary & Critical Care Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA
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Basen-Engquist K, Brown P, Coletta AM, Savage M, Maresso KC, Hawk E. Lifestyle and Cancer Prevention. ABELOFF'S CLINICAL ONCOLOGY 2020:337-374.e12. [DOI: 10.1016/b978-0-323-47674-4.00022-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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O'Keefe SJ. The association between dietary fibre deficiency and high-income lifestyle-associated diseases: Burkitt's hypothesis revisited. Lancet Gastroenterol Hepatol 2019; 4:984-996. [PMID: 31696832 PMCID: PMC6944853 DOI: 10.1016/s2468-1253(19)30257-2] [Citation(s) in RCA: 114] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2019] [Revised: 06/27/2019] [Accepted: 07/08/2019] [Indexed: 02/07/2023]
Abstract
In 1969, Denis Burkitt published an article titled "Related disease-related cause?", which became the foundation for Burkitt's hypothesis. Working in Uganda, he noted that middle-aged people (40-60 years old) had a much lower incidence of diseases that were common in similarly aged people living in England, including colon cancer, diverticulitis, appendicitis, hernias, varicose veins, diabetes, atherosclerosis, and asthma, all of which are associated with lifestyles commonly led in high-income countries (HICs; also known as western diseases). Following Cleave's common cause hypothesis-which suggests that if a group of diseases occur together in the same population or individual, they are likely to have a common cause-Burkitt attributed these diseases to the small quantities of dietary fibre consumed in HICs due mainly to the over-processing of natural foods. Nowadays, dietary fibre intake in HICs is around 15 g/day (well below the amount of fibre Burkitt advocated of >50 g/day-which is associated with diets from rural, southern and eastern sub-Sahalean Africa). Since Burkitt's death in 1993, his hypothesis has been verified and extended by large-scale epidemiological studies, which have reported that fibre deficiency increases the risk of colon, liver, and breast cancer and increases all cancer mortality and death from cardiovascular, infectious, and respiratory diseases, diabetes, and all non-cardiovascular, non-cancer causes. Furthermore, mechanistic studies have now provided molecular explanations for these associations, typified by the role of short-chain fatty acids, products of fibre fermentation in the colon, in suppressing colonic mucosal inflammation and carcinogenesis. Evidence suggests that short-chain fatty acids can affect the epigenome through metabolic regulatory receptors in distant organs, and that this can reduce obesity, diabetes, atherosclerosis, allergy, and cancer. Diseases associated with high-income lifestyles are the most serious threat to health in developed countries, and public and governmental awareness needs to be improved to urge an increase in intake of fibre-rich foods. This Viewpoint will summarise the evidence that suggests that increasing dietary fibre intake to 50 g/day is likely to increase lifespan, improve the quality of life during the added years, and substantially reduce health-care costs.
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Affiliation(s)
- Stephen J O'Keefe
- Division of Gastroenterology, University of Pittsburgh, Pittsburgh, PA, USA; African Microbiome Institute, University of Stellenbosch, Stellenbosch, South Africa.
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24
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Huang D, Lei S, Wu Y, Weng M, Zhou Y, Xu J, Xia D, Xu E, Lai M, Zhang H. Additively protective effects of vitamin D and calcium against colorectal adenoma incidence, malignant transformation and progression: A systematic review and meta-analysis. Clin Nutr 2019; 39:2525-2538. [PMID: 31784301 DOI: 10.1016/j.clnu.2019.11.012] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2019] [Revised: 10/26/2019] [Accepted: 11/07/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Colorectal cancer (CRC) exhibits a linear progression from normal colonic epithelium, adenoma initiation, carcinoma transformation and even to metastasis. Diet changes might influence carcinogenesis and prognosis. We aimed to determine the effects of vitamin D and calcium on colorectal adenoma incidence, malignancy development and prognosis. METHODS Systematic literature searches (PubMed, Embase, and Cochrane Library databases) and hand searches were performed by September 30, 2019. A random-effects model was adopted to pool relative ratios (RRs) for colorectal tumour incidence or hazard ratios (HRs) for CRC mortality. Stratified analyses were performed by gender, tumour location, calcium intake level and ethnic group. RESULTS Total 854,195 cases from 166 studies were included. The colorectal adenoma incidence was inversely correlated with the circulating 25-hydroxyvitamin D [25(OH)D] level (RR: 0.80, 95% CI: 0.71-0.89), vitamin D intake (RR: 0.87, 95% CI: 0.82-0.92) and calcium intake (RR: 0.86, 95% CI: 0.81-0.91). The CRC incidence was decreased by circulating 25(OH)D (RR: 0.67, 95% CI: 0.59-0.77), vitamin D intake (RR: 0.85, 95% CI: 0.78-0.93) and calcium intake (RR: 0.75, 95% CI: 0.70-0.79). High-level circulating 25(OH)D triggered better overall survival (HR: 0.67, 95% CI: 0.57-0.79) and CRC-specific survival (HR: 0.63, 95% CI: 0.53-0.74). Stratified analyses showed that vitamin D and calcium significantly suppressed colorectal tumour incidence among women. Left-sided CRC risk was reversely related to circulating 25(OH)D (RR: 0.60, 95% CI: 0.41-0.88) and vitamin D intake (RR: 0.73, 95% CI: 0.57-0.93). Circulating 25(OH)D decreased colorectal adenoma (RR: 0.63, 95% CI: 0.48-0.82) and CRC (RR: 0.69, 95% CI: 0.56-0.86) risk in populations with higher calcium intake. European and American populations benefited more from vitamin D intake against colorectal tumour. A significant dose-response relationship was observed between intake of vitamin D or calcium and colorectal tumour incidence. CONCLUSIONS Vitamin D and calcium play additively chemopreventive roles in colorectal adenoma incidence, malignant transformation and progression, especially for women and left-sided CRC patients.
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Affiliation(s)
- Dongdong Huang
- Department of Pathology and Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou 310058, China; Department of Pathology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Siqin Lei
- Department of Pathology and Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou 310058, China
| | - Yihua Wu
- Department of Toxicology, School of Public Health and Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China
| | - Menghan Weng
- Department of Pathology and Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou 310058, China; Department of Pathology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Yuwei Zhou
- Department of Pathology and Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China
| | - Jiawei Xu
- Department of Toxicology, School of Public Health and Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China
| | - Dajing Xia
- Department of Toxicology, School of Public Health and Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China
| | - Enping Xu
- Department of Pathology and Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou 310058, China
| | - Maode Lai
- Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou 310058, China
| | - Honghe Zhang
- Department of Pathology and Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou 310058, China.
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25
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Zhao J, Giri A, Zhu X, Shrubsole MJ, Jiang Y, Guo X, Ness R, Seidner DL, Giovannucci E, Edwards TL, Dai Q. Calcium: magnesium intake ratio and colorectal carcinogenesis, results from the prostate, lung, colorectal, and ovarian cancer screening trial. Br J Cancer 2019; 121:796-804. [PMID: 31543516 PMCID: PMC6889387 DOI: 10.1038/s41416-019-0579-2] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2019] [Revised: 08/20/2019] [Accepted: 08/28/2019] [Indexed: 12/14/2022] Open
Abstract
Background We aimed to evaluate the associations between calcium and various stages of colorectal carcinogenesis and whether these associations are modified by the calcium to magnesium (Ca:Mg) ratio. Methods We tested our hypotheses in the prostate lung, colorectal and ovarian cancer screening trial. Results Calcium intake did not show a dose–response association with incident adenoma of any size/stage (P-trend = 0.17), but followed an inverse trend when restricted to synchronous/advanced adenoma cases (P-trend = 0.05). This inverse trend was mainly in participants with Ca:Mg ratios between 1.7 and 2.5 (P-trend = 0.05). No significant associations were observed for metachronous adenoma. Calcium intake was inversely associated with CRC (P-trend = 0.03); the association was primarily present for distal CRC (P-trend = 0.01). The inverse association between calcium and distal CRC was further modified by the Ca:Mg ratio (P-interaction < 0.01); significant dose–response associations were found only in participants with a Ca:Mg ratio between 1.7 and 2.5 (P-trend = 0.04). No associations for calcium were found in the Ca:Mg ratio above 2.5 or below 1.7. Conclusion Higher calcium intake may be related to reduced risks of incident advanced and/or synchronous adenoma and incident distal CRC among subjects with Ca:Mg intake ratios between 1.7 and 2.5.
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Affiliation(s)
- Jing Zhao
- Division of Epidemiology, Vanderbilt Ingram Cancer Center, Department of Medicine, Vanderbilt University School of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Ayush Giri
- Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Xiangzhu Zhu
- Division of Epidemiology, Vanderbilt Ingram Cancer Center, Department of Medicine, Vanderbilt University School of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Martha J Shrubsole
- Division of Epidemiology, Vanderbilt Ingram Cancer Center, Department of Medicine, Vanderbilt University School of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Yixing Jiang
- Department of Medicine, Marlene and Stewart Greenebaum Cancer Center, University of Maryland, Baltimore, MD, USA
| | - Xingyi Guo
- Division of Epidemiology, Vanderbilt Ingram Cancer Center, Department of Medicine, Vanderbilt University School of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Reid Ness
- Department of Medicine, Vanderbilt Center for Human Nutrition, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Douglas L Seidner
- Department of Medicine, Vanderbilt Center for Human Nutrition, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Edward Giovannucci
- Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA, USA
| | - Todd L Edwards
- Division of Epidemiology, Vanderbilt Ingram Cancer Center, Department of Medicine, Vanderbilt University School of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Qi Dai
- Division of Epidemiology, Vanderbilt Ingram Cancer Center, Department of Medicine, Vanderbilt University School of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
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Umezawa S, Higurashi T, Komiya Y, Arimoto J, Horita N, Kaneko T, Iwasaki M, Nakagama H, Nakajima A. Chemoprevention of colorectal cancer: Past, present, and future. Cancer Sci 2019; 110:3018-3026. [PMID: 31361372 PMCID: PMC6778640 DOI: 10.1111/cas.14149] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Revised: 07/18/2019] [Accepted: 07/26/2019] [Indexed: 12/14/2022] Open
Abstract
Chemoprevention began to be considered as a potential strategy for lowering the incidence of cancer and cancer-related deaths in the 1970s. For clinical chemoprevention trials against cancer, including colorectal cancer (CRC), well-established biomarkers are necessary for use as reliable endpoints. Difficulty in establishing validated biomarkers has delayed the start of CRC chemoprevention development. Chemoprevention trials for CRC have only recently been initiated thanks to the identification of reliable biomarkers, such as colorectal adenomas and aberrant crypt foci. Some promising agents have been developed for the prevention of CRC. The chemopreventive effect of selective cyclooxygenase 2 inhibitors has been shown, although these inhibitors are associated with cardiovascular toxicity as a crucial adverse effect. Aspirin, which is a unique agent among non-steroidal anti-inflammatory drugs (NSAIDs) showing minimal gastrointestinal toxicity and no cardiovascular risk, has prevented adenoma recurrence in some randomized controlled trials. More recently, metformin, which is a first-line oral medicine for type 2 diabetes, has been shown to be safe and to prevent adenoma recurrence. A recommendation of the United States Preventive Services Task Force published in 2016 provides a Grade B recommendation for the use of aspirin for chronic prophylaxis against diseases, including CRC, in certain select populations. However, the roles of other agents have yet to be determined, and investigations to identify novel "post-aspirin" agents are also needed. The combined use of multiple drugs, such as aspirin and metformin, is another option that may lead not only to stronger CRC prevention, but also to improvement of other obesity-related diseases.
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Affiliation(s)
- Shotaro Umezawa
- Department of Gastroenterology and Hepatology, Yokohama City University, Yokohama, Japan
| | - Takuma Higurashi
- Department of Gastroenterology and Hepatology, Yokohama City University, Yokohama, Japan
| | - Yasuhiko Komiya
- Department of Gastroenterology and Hepatology, Yokohama City University, Yokohama, Japan
| | - Jun Arimoto
- Department of Gastroenterology and Hepatology, Yokohama City University, Yokohama, Japan
| | - Nobuyuki Horita
- Department of Pulmonology, Yokohama City University, Yokohama, Japan
| | - Takeshi Kaneko
- Department of Pulmonology, Yokohama City University, Yokohama, Japan
| | - Motoki Iwasaki
- Epidemiology and Prevention Group, Research center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan
| | | | - Atsushi Nakajima
- Department of Gastroenterology and Hepatology, Yokohama City University, Yokohama, Japan
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Hosseinzadeh P, Javanbakht M, Alemrajabi M, Gholami A, Amirkalali B, Sohrabi M, Zamani F. The Association of Dietary Intake of Calcium and Vitamin D to Colorectal Cancer Risk among Iranian Population. Asian Pac J Cancer Prev 2019; 20:2825-2830. [PMID: 31554383 PMCID: PMC6976838 DOI: 10.31557/apjcp.2019.20.9.2825] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2019] [Accepted: 09/12/2019] [Indexed: 02/06/2023] Open
Abstract
Background: Vitamin D and Calcium have a possible protective impact versus rectal neoplasm. Vitamin D, an important nutrient, is vital to regulate the absorption of calcium and bone mineralization; nevertheless, in a case-control study in Iran, we investigated the relationship among the dietary intake of vitamin D and calcium with the hazard of rectal neoplasm. Methods: 363 subjects (162 cases and 201 controls) participated in the case- control Study from March 2017 to November 2018. Dietary intake of Calcium and Vitamin D was calculated using a 148-items food-frequency questionnaire. Results: Since altering the strong confounding agents, the multivariate risk proportion within the dietary vitamin D intake was OR=0.2, 95%CI 0.1-0.5, P-value <0.001 among cases. There was no association in case of calcium and rectal cancer. Conclusions: Taken together, a possible reduction in the hazard of rectal neoplasm with dietary intake of Vitamin D within Iranian patients was observed.
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Affiliation(s)
- Payam Hosseinzadeh
- Gastrointestinal and Liver Diseases Research Center (GILDRC), Iran University of Medical Sciences (IUMS), Tehran, Iran.
| | - Mohammad Javanbakht
- Nephrology and Urology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Mahdi Alemrajabi
- Firoozgar Hospital, FCRDC, Iran University of Medical Sciences, Tehran, Iran
| | - Ali Gholami
- Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran
- Department of Epidemiology and Biostatistics, School of Public Health, Neyshabur University of Medical Sciences, Neyshabur, Iran
| | - Bahare Amirkalali
- Gastrointestinal and Liver Diseases Research Center (GILDRC), Iran University of Medical Sciences (IUMS), Tehran, Iran.
| | - Masoudreza Sohrabi
- Gastrointestinal and Liver Diseases Research Center (GILDRC), Iran University of Medical Sciences (IUMS), Tehran, Iran.
| | - Farhad Zamani
- Gastrointestinal and Liver Diseases Research Center (GILDRC), Iran University of Medical Sciences (IUMS), Tehran, Iran.
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Skiba MB, Kohler LN, Crane TE, Jacobs ET, Shadyab AH, Kato I, Snetselaar L, Qi L, Thomson CA. The Association between Prebiotic Fiber Supplement Use and Colorectal Cancer Risk and Mortality in the Women's Health Initiative. Cancer Epidemiol Biomarkers Prev 2019; 28:1884-1890. [PMID: 31455673 DOI: 10.1158/1055-9965.epi-19-0326] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Revised: 06/07/2019] [Accepted: 08/20/2019] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND Fiber-based prebiotic supplements are marketed for maintaining bowel health and promoting beneficial gut bacteria. However, the association between prebiotic supplement use and colorectal cancer risk and mortality is unknown. METHODS The association between prebiotic use and colorectal cancer risk and mortality was evaluated in postmenopausal women in the Women's Health Initiative study. Self-reported prebiotic use was documented at study enrollment. Adjudicated colorectal cancer cases and mortality were captured using medical and death records. Cox proportional hazards models were used to estimate the HR related to prebiotic use and colorectal cancer risk and mortality. RESULTS In total, 3,032 colorectal cancer cases were diagnosed during an average 15.4 years of follow-up. Overall, 3.7% of women used a prebiotic with psyllium, the major fiber type. Use of any prebiotic supplement was not associated with colorectal cancer risk or mortality. The type of prebiotic supplement (none vs. insoluble or soluble) was not associated with colorectal cancer risk; however, use of insoluble fiber prebiotics compared with none was associated with higher colorectal cancer mortality [HR, 2.79; 95% confidence interval (CI), 1.32-5.90; P = 0.007]. Likelihood ratio tests indicated no significant interactions between prebiotic use and other colorectal cancer risk factors, including metabolic syndrome. CONCLUSIONS Prebiotic fiber supplement use was not associated with colorectal cancer risk. Insoluble, but not soluble, prebiotic fiber use was associated with higher colorectal cancer mortality. These findings do not support the promotion of prebiotic fiber supplements to reduce colorectal cancer risk or colorectal cancer mortality. IMPACT Further investigation is warranted for findings regarding insoluble prebiotic fiber and higher colorectal cancer mortality in postmenopausal women.
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Affiliation(s)
- Meghan B Skiba
- Department of Health Promotion Sciences, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona
| | - Lindsay N Kohler
- Department of Health Promotion Sciences, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona.,Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona
| | - Tracy E Crane
- Department of Biobehavioral Sciences, College of Nursing, University of Arizona, Tucson, Arizona
| | - Elizabeth T Jacobs
- Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona
| | - Aladdin H Shadyab
- Department of Family Medicine and Public Health, University of California San Diego School of Medicine, La Jolla, California
| | - Ikuko Kato
- Department of Oncology and Pathology, Wayne State University, Detroit, Michigan
| | - Linda Snetselaar
- Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa
| | - Lihong Qi
- Department of Public Health, School of Medicine, University of California-Davis, Davis, California
| | - Cynthia A Thomson
- Department of Health Promotion Sciences, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona.
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29
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Association between grains, gluten and the risk of colorectal cancer in the Cancer Prevention Study-II Nutrition Cohort. Eur J Nutr 2019; 59:1739-1749. [DOI: 10.1007/s00394-019-02032-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Accepted: 06/15/2019] [Indexed: 12/22/2022]
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30
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Calderwood AH, Baron JA, Mott LA, Ahnen DJ, Bostick RM, Figueiredo JC, Passarelli MN, Rees JR, Robertson DJ, Barry EL. No Evidence for Posttreatment Effects of Vitamin D and Calcium Supplementation on Risk of Colorectal Adenomas in a Randomized Trial. Cancer Prev Res (Phila) 2019; 12:295-304. [PMID: 30833381 DOI: 10.1158/1940-6207.capr-19-0023] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Revised: 02/25/2019] [Accepted: 02/25/2019] [Indexed: 12/15/2022]
Abstract
Vitamin D and calcium supplementation are postulated to have chemopreventive effects against colorectal neoplasia, yet in our previously reported randomized trial, there was no overall efficacy of calcium and/or vitamin D3 against colorectal adenoma recurrence. It is possible vitamin D3 and calcium chemopreventive effects are not detectable until beyond the 3- to 5-year follow-up captured in that trial. Accordingly, we explored possible vitamin D and calcium effects on posttreatment (observational) adenoma occurrence. In this secondary analysis of the observational follow-up phase of the Vitamin D/Calcium Polyp Prevention Study, participants who completed the treatment phase were invited to be followed for one additional surveillance colonoscopy cycle. We evaluated adenoma occurrence risk at surveillance colonoscopy, with a mean of 55 ± 15 months after treatment follow-up, according to randomized treatment with vitamin D versus no vitamin D, calcium versus no calcium, and calcium plus vitamin D versus calcium alone. Secondary outcomes included advanced and multiple adenomas. Among the 1,121 participants with observational follow-up, the relative risk (95% confidence interval, CI) of any adenoma was 1.04 (0.93-1.17) for vitamin D versus no vitamin D; 0.95 (0.84-1.08) for calcium versus no calcium; 1.07 (0.91-1.25) for calcium plus vitamin D versus calcium; and 0.96 (0.81-1.15) for calcium plus vitamin D versus neither. Risks of advanced or multiple adenomas also did not differ by treatment. Our results do not support an association between supplemental calcium and/or vitamin D3 for 3 to 5 years and risk of recurrent colorectal adenoma at an average of 4.6 years after treatment.
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Affiliation(s)
- Audrey H Calderwood
- Section of Gastroenterology and Hepatology, Department of Medicine, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.
| | - John A Baron
- Departments of Epidemiology and Medicine, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire; University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Leila A Mott
- Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire
| | - Dennis J Ahnen
- Division of Gastroenterology and Hepatology, University of Colorado School of Medicine, Denver, Colorado
| | - Roberd M Bostick
- Department of Epidemiology, Emory University; Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Jane C Figueiredo
- Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Michael N Passarelli
- Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire
| | - Judy R Rees
- Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire
| | - Douglas J Robertson
- VA Medical Center, White River Junction, Vermont; Section of Gastroenterology and Hepatology, Department of Medicine, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire
| | - Elizabeth L Barry
- Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire
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31
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Crockett SD, Barry EL, Mott LA, Ahnen DJ, Robertson DJ, Anderson JC, Wallace K, Burke CA, Bresalier RS, Figueiredo JC, Snover DC, Baron JA. Calcium and vitamin D supplementation and increased risk of serrated polyps: results from a randomised clinical trial. Gut 2019; 68:475-486. [PMID: 29496722 PMCID: PMC6286251 DOI: 10.1136/gutjnl-2017-315242] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2017] [Revised: 12/18/2017] [Accepted: 01/05/2018] [Indexed: 12/15/2022]
Abstract
OBJECTIVE Serrated lesions such as sessile serrated adenomas or polyps (SSA/Ps) are important colorectal cancer precursors, but aetiological factors for these lesions are largely unknown. We aimed to determine the effects of calcium and vitamin D supplementation on the incidence of serrated polyps (SPs) in general and hyperplastic polyps and SSA/Ps specifically. DESIGN Participants with one or more adenoma at baseline were randomised to receive 1200 mg/day of elemental calcium, 1000 IU/day of vitamin D3, both or neither agent. Treatment continued for 3 or 5 years, when risk of polyps was determined from surveillance colonoscopy (treatment phase). Outcomes after treatment ceased were also assessed (observational phase). Adjusted risk ratios (aRRs) of SPs were determined via multivariable generalised linear models. RESULTS SPs were diagnosed in 565 of 2058 (27.5%) participants during the treatment phase and 329/1108 (29.7%) during the observational phase. In total, 211 SSA/Ps were identified during follow-up. In the treatment phase, there was no effect of either calcium or vitamin D on incidence of SSA/Ps. However, during the later observational phase, we observed elevated risks of SSA/Ps associated with calcium alone and calcium+vitamin D treatment (aRR (95% CI): 2.65 (1.43 to 4.91) and 3.81 (1.25 to 11.64), respectively). CONCLUSION In a large multicentre chemoprevention study, we found evidence that calcium and vitamin D supplementation increased the risk of SSA/Ps. This appeared to be a late effect: 6-10 years after supplementation began. These possible risks must be weighed against the benefits of calcium and vitamin D supplementation. : Trial registration NUMBER: NCT00153816; Results.
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Affiliation(s)
- Seth D. Crockett
- Division of Gastroenterology and Hepatology, University of
North Carolina School of Medicine, Chapel Hill, NC
| | - Elizabeth L. Barry
- Department of Epidemiology, Geisel School of Medicine at
Dartmouth, Lebanon, NH
| | - Leila A. Mott
- Department of Epidemiology, Geisel School of Medicine at
Dartmouth, Lebanon, NH
| | - Dennis J. Ahnen
- Division of Gastroenterology, University of Colorado School
of Medicine, Aurora CO
| | - Douglas J. Robertson
- Division of Gastroenterology and Hepatology, VA Medical
Center, White River Junction, VT & Geisel School of Medicine at Dartmouth,
Hanover, NH
| | - Joseph C. Anderson
- Division of Gastroenterology and Hepatology, VA Medical
Center, White River Junction, VT & Geisel School of Medicine at Dartmouth,
Hanover, NH
| | - Kristen Wallace
- Department of Public Health Sciences, Medical University of
South Carolina, Charleston, SC
| | - Carol A. Burke
- Department of Gastroenterology, Cleveland Clinic School of
Medicine, Cleveland, OH
| | - Robert S. Bresalier
- Department of Gastroenterology, University of Texas MD
Anderson Cancer Center, Houston, TX
| | - Jane C. Figueiredo
- Department of Preventive Medicine, Keck School of Medicine,
University of Southern California, Los Angeles, CA
| | - Dale C. Snover
- Department of Pathology, Fairview Southdale Hospital,
Edina, MN
| | - John A. Baron
- Division of Gastroenterology and Hepatology, University of
North Carolina School of Medicine, Chapel Hill, NC
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32
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Song M, Chan AT. Environmental Factors, Gut Microbiota, and Colorectal Cancer Prevention. Clin Gastroenterol Hepatol 2019; 17:275-289. [PMID: 30031175 PMCID: PMC6314893 DOI: 10.1016/j.cgh.2018.07.012] [Citation(s) in RCA: 226] [Impact Index Per Article: 37.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2018] [Revised: 07/02/2018] [Accepted: 07/06/2018] [Indexed: 02/07/2023]
Abstract
The substantial burden of colorectal cancer and increasing trend in young adults highlight the importance of lifestyle modification as a complement to screening for colorectal cancer prevention. Several dietary and lifestyle factors have been implicated in the development of colorectal cancer, possibly through the intricate metabolic and inflammatory mechanisms. Likewise, as a key metabolic and immune regulator, the gut microbiota has been recognized to play an important role in colorectal tumorigenesis. Increasing data support that environmental factors are crucial determinants for the gut microbial composition and function, whose alterations induce changes in the host gene expression, metabolic regulation, and local and systemic immune response, thereby influencing cancer development. Here, we review the epidemiologic and mechanistic evidence regarding the links between diet and lifestyle and the gut microbiota in the development of colorectal cancer. We focus on factors for which substantial data support their importance for colorectal cancer and their potential role in the gut microbiota, including overweight and obesity, physical activity, dietary patterns, fiber, red and processed meat, marine omega-3 fatty acid, alcohol, and smoking. We also briefly describe other colorectal cancer-preventive factors for which the links with the gut microbiota have been suggested but remain to be mechanistically characterized, including vitamin D status, dairy consumption, and metformin use. Given limitations in available evidence, we highlight the need for further investigations in the relationship between environmental factors, gut microbiota, and colorectal cancer, which may lead to development and clinical translation of potential microbiota-based strategies for cancer prevention.
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Affiliation(s)
- Mingyang Song
- Departments of Epidemiology and Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA
| | - Andrew T. Chan
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA
- Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA
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33
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Kwan AK, Um CY, Rutherford RE, Seabrook ME, Barry EL, Fedirko V, Baron JA, Bostick RM. Effects of vitamin D and calcium on expression of MSH2 and transforming growth factors in normal-appearing colorectal mucosa of sporadic colorectal adenoma patients: A randomized clinical trial. Mol Carcinog 2018; 58:511-523. [PMID: 30499618 DOI: 10.1002/mc.22945] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2018] [Revised: 09/24/2018] [Accepted: 11/22/2018] [Indexed: 12/14/2022]
Abstract
Abnormal expression of the DNA mismatch repair protein MSH2 and autocrine/paracrine transforming growth factors TGFα (growth promoter) and TGFβ1 (growth inhibitor) is common during colorectal carcinogenesis. To estimate vitamin D and calcium effects on these biomarkers in the normal-appearing colorectal mucosa of sporadic colorectal adenoma patients, we conducted a pilot, randomized, double-blinded, placebo-controlled, modified 2 × 2 factorial chemoprevention clinical trial (N = 104) of supplemental vitamin D3 (1000 IU daily) and calcium (1200 mg daily), alone and in combination, versus placebo over 1 year. The expression of the three biomarkers and Ki-67/mib-1 in colorectal crypts in biopsies of normal-appearing rectal mucosa were detected using automated immunohistochemistry and quantified using image analysis. In the vitamin D3 and vitamin D3 plus calcium groups, relative to their reference groups, in the upper 40% (differentiation zone) of crypts, it was estimated that, respectively, the MSH2/mib-1 ratio increased by 47% (P = 0.14) and 62% (P = 0.08), TGFβ1 expression increased by 41% (P = 0.25) and 78% (P = 0.14), and the TGFα/TGFβ1 ratio decreased by 25% (P = 0.31) and 44% (P = 0.13). Although not statistically significant, these results support further research into (i) whether supplemental vitamin D3 , alone or in combination with calcium, may increase DNA mismatch repair relative to proliferation, increase TGFβ1 expression, and decrease autocrine/paracrine growth promotion relative to growth inhibition in the colorectal epithelium, all hypothesized to reduce risk for colorectal carcinogenesis; and (ii) the expression of MSH2 relative to mib-1, TGFβ1 alone, and TGFα relative to TGFβ1 in the normal-appearing rectal mucosa as potential modifiable, pre-neoplastic markers of risk for colorectal neoplasms.
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Affiliation(s)
- Albert K Kwan
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia
| | - Caroline Y Um
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia
| | - Robin E Rutherford
- Division of Digestive Diseases, Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia
| | | | - Elizabeth L Barry
- Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire
| | - Veronika Fedirko
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia.,Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - John A Baron
- Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire.,Department of Medicine, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire.,University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Roberd M Bostick
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia.,Winship Cancer Institute, Emory University, Atlanta, Georgia
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Um CY, Prizment A, Hong CP, Lazovich D, Bostick RM. Associations of Calcium, Vitamin D, and Dairy Product Intakes with Colorectal Cancer Risk among Older Women: The Iowa Women's Health Study. Nutr Cancer 2018; 71:739-748. [PMID: 30572720 DOI: 10.1080/01635581.2018.1539188] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Calcium and, to a lesser extent, dairy products are consistently modestly inversely associated with colorectal cancer (CRC). Dairy products may contain components other than calcium and fat, such as insulin-like growth factor-1, that may affect CRC risk. In the prospective Iowa Women's Health Study, calcium, dairy product, and vitamin D intakes were assessed using a semiquantitative food frequency questionnaire. To investigate dairy products independent of their calcium components, we estimated residuals from linear regression models of their associations with dietary calcium. Of the 35,221 55-69-year-old cancer-free women at baseline in 1986, 1,731 developed CRC during follow-up through 2012. For those in the highest relative to the lowest intake quintiles, the adjusted hazards ratios and 95% confidence intervals from multivariable Cox proportional hazards regression models for overall and distal CRC were 0.81 (0.67-0.98; Ptrend = 0.004) and 0.59 (0.44-0.80; Ptrend = 0.003), respectively, for total calcium; and 0.79 (0.66-0.94; Ptrend = 0.01) and 0.69 (0.53-0.90; Ptrend = 0.003) for total dairy products, respectively. The various dairy product residuals were not associated with CRC. These results support that, among women, calcium and dairy products may be inversely associated with CRC-perhaps primarily distal CRC-but suggest that the non-calcium, non-fat component of dairy products may not be associated with CRC.
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Affiliation(s)
- Caroline Y Um
- a Department of Epidemiology, Rollins School of Public Health , Emory University , Atlanta , Georgia , USA
| | - Anna Prizment
- b Division of Epidemiology and Community Health, School of Public Health , University of Minnesota , Minneapolis , Minnesota , USA.,c Masonic Cancer Center, University of Minnesota , Minneapolis , Minnesota , USA
| | - Ching-Ping Hong
- b Division of Epidemiology and Community Health, School of Public Health , University of Minnesota , Minneapolis , Minnesota , USA
| | - DeAnn Lazovich
- b Division of Epidemiology and Community Health, School of Public Health , University of Minnesota , Minneapolis , Minnesota , USA.,c Masonic Cancer Center, University of Minnesota , Minneapolis , Minnesota , USA
| | - Roberd M Bostick
- a Department of Epidemiology, Rollins School of Public Health , Emory University , Atlanta , Georgia , USA.,d Winship Cancer Institute, Emory University , Atlanta , Georgia , USA
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Gao Y, Um CY, Fedirko V, Rutherford RE, Seabrook ME, Barry EL, Baron JA, Bostick RM. Effects of supplemental vitamin D and calcium on markers of proliferation, differentiation, and apoptosis in the normal colorectal mucosa of colorectal adenoma patients. PLoS One 2018; 13:e0208762. [PMID: 30557404 PMCID: PMC6296527 DOI: 10.1371/journal.pone.0208762] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2018] [Accepted: 10/18/2018] [Indexed: 12/14/2022] Open
Abstract
To clarify the roles of vitamin D and calcium as potential chemopreventive agents against colorectal cancer in humans, and to develop “treatable”, pre-neoplastic, phenotypic biomarkers of risk for colorectal neoplasms, we estimated the effects of supplemental vitamin D3 (1,000 IU/day [25 μg/day]) and calcium (1,200 mg/day), alone and in combination, on biomarkers of proliferation (mib-1), differentiation (p21), and apoptosis (bax [apoptosis-promoting] and bcl-2 [apoptosis-inhibiting]), in the normal-appearing rectal mucosa in a subsample of participants (n = 104) in a larger randomized, double-blind, placebo-controlled clinical trial among colorectal adenoma patients. The biomarkers were measured in rectal biopsies at baseline and after one year of follow up, using automated immunohistochemistry and quantitative image analysis. In the vitamin D plus calcium group relative to control, in the crypt differentiation zone (upper 40% of crypts), mib-1 expression decreased 24% (P = 0.28); p21 expression alone and relative to mib-1 expression increased 29% (P = 0.06) and 73% (P = 0.06), respectively; and bax expression relative to mib-1 expression increased 58% (P = 0.21). The estimated vitamin D alone treatment effects were similar but of lesser magnitudes, and those for calcium alone were mixed. All estimated treatment effects on bcl-2 expression were close to the null. These pilot study results support further investigation of whether 1) vitamin D and calcium promote colorectal epithelial cell differentiation, reduce proliferation, and promote apoptosis in the normal-appearing human colorectal mucosa, 2) vitamin D and calcium act as chemopreventive agents against colorectal neoplasms, and 3) mib-1, p21, and bax are potential “treatable”, pre-neoplastic, biomarkers of risk for colorectal neoplasms.
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Affiliation(s)
- Yasheen Gao
- Department of Epidemiology, Emory University, Atlanta, Georgia, United States of America
| | - Caroline Y. Um
- Department of Epidemiology, Emory University, Atlanta, Georgia, United States of America
| | - Veronika Fedirko
- Department of Epidemiology, Emory University, Atlanta, Georgia, United States of America
- Winship Cancer Institute, Emory University, Atlanta, Georgia, United States of America
| | - Robin E. Rutherford
- Division of Digestive Diseases, Department of Medicine, School of Medicine, Emory University, Georgia, United States of America
| | - March E. Seabrook
- Consultants in Gastroenterology, West Columbia, South Carolina, United States of America
| | - Elizabeth L. Barry
- Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, United States of America
| | - John A. Baron
- Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, United States of America
- Department of Medicine, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, United States of America
- University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America
| | - Roberd M. Bostick
- Department of Epidemiology, Emory University, Atlanta, Georgia, United States of America
- Winship Cancer Institute, Emory University, Atlanta, Georgia, United States of America
- * E-mail:
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36
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Yang W, Ma Y, Smith-Warner S, Song M, Wu K, Wang M, Chan AT, Ogino S, Fuchs CS, Poylin V, Ng K, Meyerhardt JA, Giovannucci EL, Zhang X. Calcium Intake and Survival after Colorectal Cancer Diagnosis. Clin Cancer Res 2018; 25:1980-1988. [PMID: 30545821 DOI: 10.1158/1078-0432.ccr-18-2965] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2018] [Revised: 10/24/2018] [Accepted: 12/10/2018] [Indexed: 01/05/2023]
Abstract
PURPOSE Although evidence suggests an inverse association between calcium intake and colorectal cancer incidence, the influence of calcium on survival after colorectal cancer diagnosis remains unclear.Experimental Design: We prospectively assessed the association of postdiagnostic calcium intake with colorectal cancer-specific and overall mortality among 1,660 nonmetastatic colorectal cancer patients within the Nurses' Health Study and the Health Professionals Follow-up Study. Patients completed a validated food frequency questionnaire between 6 months and 4 years after diagnosis and were followed up for death. Multivariable hazard ratios (HRs) and 95% confidence intervals (95% CI) were calculated using Cox proportional hazards regression. RESULTS Comparing the highest with the lowest quartile intake of postdiagnostic total calcium, the multivariable HRs were 0.56 (95% CI, 0.32-0.96; P trend = 0.04) for colorectal cancer-specific mortality and 0.80 (95% CI, 0.59-1.09; P trend = 0.11) for all-cause mortality. Postdiagnostic supplemental calcium intake was also inversely associated with colorectal cancer-specific mortality (HR, 0.67; 95% CI, 0.42-1.06; P trend = 0.047) and all-cause mortality (HR, 0.71; 95% CI, 0.54-0.94; P trend = 0.008), although these inverse associations were primarily observed in women. In addition, calcium from diet or dairy sources was associated with lower risk in men. CONCLUSIONS Higher calcium intake after the diagnosis may be associated with a lower risk of death among patients with colorectal cancer. If confirmed, these findings may provide support for the nutritional recommendations of maintaining sufficient calcium intake among colorectal cancer survivors.
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Affiliation(s)
- Wanshui Yang
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Yanan Ma
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.,Department of Biostatistics and Epidemiology, School of Public Health, China Medical University, Shenyang, Liaoning, P.R. China
| | - Stephanie Smith-Warner
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Mingyang Song
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.,Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.,Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts
| | - Kana Wu
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Molin Wang
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Andrew T Chan
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.,Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.,Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts.,Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Shuji Ogino
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.,Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.,Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Charles S Fuchs
- Department of Medical Oncology, Yale Cancer Center, New Haven, Connecticut.,Department of Medicine, Yale School of Medicine, New Haven, Connecticut.,Department of Medical Oncology, Smilow Cancer Hospital, New Haven, Connecticut
| | - Vitaliy Poylin
- Department of Surgery, Division of Colon and Rectal Surgery, Beth Israel Deaconess Medical Center in Boston, Massachusetts
| | - Kimmie Ng
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts
| | - Jeffrey A Meyerhardt
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts
| | - Edward L Giovannucci
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.,Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Xuehong Zhang
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
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Gapstur SM, Drope JM, Jacobs EJ, Teras LR, McCullough ML, Douglas CE, Patel AV, Wender RC, Brawley OW. A blueprint for the primary prevention of cancer: Targeting established, modifiable risk factors. CA Cancer J Clin 2018; 68:446-470. [PMID: 30303518 DOI: 10.3322/caac.21496] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2018] [Revised: 08/15/2018] [Accepted: 08/15/2018] [Indexed: 01/27/2023] Open
Abstract
In the United States, it is estimated that more than 1.7 million people will be diagnosed with cancer, and more than 600,000 will die of the disease in 2018. The financial costs associated with cancer risk factors and cancer care are enormous. To substantially reduce both the number of individuals diagnosed with and dying from cancer and the costs associated with cancer each year in the United States, government and industry and the public health, medical, and scientific communities must work together to develop, invest in, and implement comprehensive cancer control goals and strategies at the national level and expand ongoing initiatives at the state and local levels. This report is the second in a series of articles in this journal that, together, describe trends in cancer rates and the scientific evidence on cancer prevention, early detection, treatment, and survivorship to inform the identification of priorities for a comprehensive cancer control plan. Herein, we focus on existing evidence about established, modifiable risk factors for cancer, including prevalence estimates and the cancer burden due to each risk factor in the United States, and established primary prevention recommendations and interventions to reduce exposure to each risk factor.
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Affiliation(s)
- Susan M Gapstur
- Senior Vice President, Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA
| | - Jeffrey M Drope
- Vice President, Economic & Health Policy Research, American Cancer Society, Atlanta, GA
| | - Eric J Jacobs
- Senior Scientific Director, Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA
| | - Lauren R Teras
- Senior Principal Scientist, Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA
| | - Marjorie L McCullough
- Senior Scientific Director, Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA
| | - Clifford E Douglas
- Vice President, Tobacco Control, and Director, Center for Tobacco Control, American Cancer Society, Atlanta, GA
| | - Alpa V Patel
- Senior Scientific Director, Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA
| | - Richard C Wender
- Chief Cancer Control Officer, American Cancer Society, Atlanta, GA
| | - Otis W Brawley
- Chief Medical and Scientific Officer and Executive Vice President of Research, American Cancer Society, Atlanta, GA
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Jenkins DJ, Spence JD, Giovannucci EL, Kim YI, Josse R, Vieth R, Blanco Mejia S, Viguiliouk E, Nishi S, Sahye-Pudaruth S, Paquette M, Patel D, Mitchell S, Kavanagh M, Tsirakis T, Bachiri L, Maran A, Umatheva N, McKay T, Trinidad G, Bernstein D, Chowdhury A, Correa-Betanzo J, Del Principe G, Hajizadeh A, Jayaraman R, Jenkins A, Jenkins W, Kalaichandran R, Kirupaharan G, Manisekaran P, Qutta T, Shahid R, Silver A, Villegas C, White J, Kendall CW, Pichika SC, Sievenpiper JL. Supplemental Vitamins and Minerals for CVD Prevention and Treatment. J Am Coll Cardiol 2018; 71:2570-2584. [DOI: 10.1016/j.jacc.2018.04.020] [Citation(s) in RCA: 145] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2017] [Revised: 03/26/2018] [Accepted: 04/17/2018] [Indexed: 12/14/2022]
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Noguti J, Chan AA, Bandera B, Brislawn CJ, Protic M, Sim MS, Jansson JK, Bilchik AJ, Lee DJ. Both the intratumoral immune and microbial microenvironment are linked to recurrence in human colon cancer: results from a prospective, multicenter nodal ultrastaging trial. Oncotarget 2018; 9:23564-23576. [PMID: 29805756 PMCID: PMC5955112 DOI: 10.18632/oncotarget.25276] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2018] [Accepted: 04/08/2018] [Indexed: 12/15/2022] Open
Abstract
Colon cancer (CC) is the third most common cancer diagnosed in the United States and the incidence has been rising among young adults. We and others have shown a relationship between the immune infiltrate and prognosis, with improved disease-free survival (DFS) being associated with a higher expression of CD8+ T cells. We hypothesized that a microbial signature might be associated with intratumoral immune cells as well as DFS. We found that the relative abundance of one Operational Taxonomic Unit (OTU), OTU_104, was significantly associated with recurrence even after applying false discovery correction (HR 1.21, CI 1.08 to 1.36). The final multivariable model showed that DFS was influenced by three parameters: N-stage, CD8+ labeling, as well as this OTU_104 belonging to the order Clostridiales. Not only were CD8+ labeling and OTU_104 significant contributors in the final DFS model, but they were also inversely correlated to each other (p=0.022). Interestingly, CD8+ was also significantly associated with the microbiota composition in the tumor: CD8+ T cells was inversely correlated with alpha diversity (p=0.027) and significantly associated with the beta diversity. This study is the first to demonstrate an association among the intratumoral microbiome, CD8+ T cells, and recurrence in CC. An increased relative abundance of a specific OTU_104 was inversely associated with CD8+ T cells and directly associated with CC recurrence. The link between this microbe, CD8+ T cells, and DFS has not been previously shown.
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Affiliation(s)
- Juliana Noguti
- Dirks/Dougherty Laboratory for Cancer Research, Department of Translational Immunology, John Wayne Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, USA.,Los Angeles Biomedical Research Institute, Harbor - UCLA Medical Center, Torrance, CA, USA
| | - Alfred A Chan
- Dirks/Dougherty Laboratory for Cancer Research, Department of Translational Immunology, John Wayne Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, USA.,Los Angeles Biomedical Research Institute, Harbor - UCLA Medical Center, Torrance, CA, USA
| | - Bradley Bandera
- Department of Surgical Oncology. The John Wayne Cancer Institute at Providence St. John's Health Center, Santa Monica, CA, USA
| | - Colin J Brislawn
- Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, Washington, USA
| | - Mladjan Protic
- University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia.,Oncology Institute of Vojvodina, Sremska Kamenica, Serbia
| | - Myung S Sim
- UCLA Department of Medicine, Statistics Core, Los Angeles, CA, USA
| | - Janet K Jansson
- Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, Washington, USA
| | - Anton J Bilchik
- Department of Surgical Oncology. The John Wayne Cancer Institute at Providence St. John's Health Center, Santa Monica, CA, USA
| | - Delphine J Lee
- Dirks/Dougherty Laboratory for Cancer Research, Department of Translational Immunology, John Wayne Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, USA.,Los Angeles Biomedical Research Institute, Harbor - UCLA Medical Center, Torrance, CA, USA.,Division of Dermatology, Department of Medicine, Harbor - UCLA Medical Center, Torrance, CA, USA.,David Geffen School of Medicine, University of California - Los Angeles, Los Angeles, CA, USA
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Stoffel EM. Updates on Translational Research on Prevention of Polyps and Colorectal Cancer. Clin Colon Rectal Surg 2018; 31:153-160. [PMID: 29720901 DOI: 10.1055/s-0037-1602235] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Morbidity and mortality from colorectal cancer (CRC) can be effectively reduced through early detection and prevention. To date, strategies for managing CRC risk have focused primarily on secondary prevention, through screening asymptomatic individuals for colorectal neoplasia. In the United States, implementation of screening among individuals age ≥50 has led to not only decreased CRC-related mortality but also reduced CRC incidence through colonoscopic removal of precancerous polyps. In contrast to screening's endpoint of early detection, the goal of primary prevention of CRC is to arrest and/or reverse colorectal carcinogenesis. Observational studies and randomized clinical trials continue to examine effects of specific pharmacologic agents (chemoprevention) and dietary interventions on development of advanced colorectal neoplasia. This review will present an overview of strategies for primary and secondary prevention of CRC, including endoscopic, pharmacologic, and dietary interventions.
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Affiliation(s)
- Elena M Stoffel
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
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Xu K, Dai H, Wang S, Zhang J, Liu T. The CXCL12 rs1801157 polymorphism and risk of colorectal cancer: a meta-analysis. Onco Targets Ther 2018; 11:2445-2452. [PMID: 29760554 PMCID: PMC5937488 DOI: 10.2147/ott.s151514] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND The CXCL12 rs1801157 polymorphism is putatively associated with the risk of malignancy. However, research results are inconsistent regarding particular cancers, especially colorectal cancer (CRC). METHODS We conducted a meta-analysis via a comprehensive literature search of the databases PubMed and Embase. Odds ratios and their corresponding 95% confidence intervals were extracted to assess comprehensively the association between the CXCL12 rs1801157 polymorphism and the risk of CRC. RESULTS According to the following models, the correlation between the presence of the CXCL12 rs1801157 polymorphism and the risk of CRC was not statistically significant: allelic (G cf. A), heterozygous (GG cf. GA), homozygous (GG cf. AA), dominant (GG cf. GA+AA), or recessive (AA cf. GA+GG) for pooled calculating. However, in subgroup analysis, elevated risk of CRC was found in the non-Caucasian group in four genetic models, while no connection was found in the Caucasian group. The sensitivity analysis confirmed that the result of the Caucasian group was stable and analyzed the heterogeneity of the non-Caucasian group. CONCLUSION This meta-analysis suggested that the CXCL12 rs1801157 polymorphism did not significantly confer a risk of CRC among Caucasians but may among non-Caucasians. These results warrant confirmation and further studies of different ethnic populations.
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Affiliation(s)
- Ke Xu
- Department of Oncology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China
| | - Hong Dai
- Department of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, People’s Republic of China
| | - Shaolong Wang
- Department of Oncology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China
| | - Jie Zhang
- Department of Oncology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China
| | - Tao Liu
- Department of Oncology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China
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Shi X, Yang Z, Wu Q, Fan D. Colorectal adenoma recurrence rates among post-polypectomy patients in the placebo-controlled groups of randomized clinical trials: a meta-analysis. Oncotarget 2017; 8:62371-62381. [PMID: 28977952 PMCID: PMC5617512 DOI: 10.18632/oncotarget.18181] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2017] [Accepted: 04/14/2017] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Evidence regarding the benefit of therapy to prevent the post-polypectomy recurrence of colorectal adenoma is limited. Endoscopic recurrence is the main outcome according to an evaluation of trials involving recurrence prevention. AIM To estimate the recurrence rates of post-polypectomy colorectal adenoma in placebo-controlled arms of randomized clinical trials and to identify the prognostic factors influencing these rates. METHODS We combined data from all randomized controlled trials evaluating therapies for colorectal adenoma using placebo from 1988 to 2016. The data were combined in a random-effects model. Primary outcomes were endoscopic adenoma and advanced adenoma recurrence of colorectal adenoma. RESULTS The pooled estimates of the adenoma recurrence rates were 37% (95% confidence interval [CI], 33%-41%; range, 33%-52%) at 1 year, 47% (95% CI, 41%-54%; range, 46%-51%) at 2 years, 41% (95% CI, 33%-48%; range, 20%-61%) at 3 years, 48% (95% CI, 38%-57%; range, 37%-53%) at 4 years, and 60% (95% CI, 52%-68%; range, 48%-68%) at 5 years. The pooled estimates of the advanced adenoma recurrence rates were 10% (95% CI, 6%-15%; range, 7%-13%) at 1 year, 12% (95% CI, 8%-16%; range, 3%-19%) at 3 years, 14% (95% CI, 10%-18%; range, 13%-16%) at 4 years, and 14% (95% CI, 10%-19%; range, 9%-21%) at 5 years. Significant heterogeneity among the randomized clinical trials (P < 0.001) was observed for each recurrence rate. CONCLUSIONS This meta-analysis confirms the heterogeneity of recurrence rates among post-polypectomy colorectal adenoma patients who received placebo. No single design variable was identified that might explain the heterogeneity.
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Affiliation(s)
- Xin Shi
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
| | - Zhiping Yang
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
| | - Qiong Wu
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
| | - Daiming Fan
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
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Shaw E, Warkentin MT, McGregor SE, Town S, Hilsden RJ, Brenner DR. Intake of dietary fibre and lifetime non-steroidal anti-inflammatory drug (NSAID) use and the incidence of colorectal polyps in a population screened for colorectal cancer. J Epidemiol Community Health 2017; 71:961-969. [PMID: 28847844 PMCID: PMC5754858 DOI: 10.1136/jech-2016-208606] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2016] [Revised: 07/06/2017] [Accepted: 08/12/2017] [Indexed: 12/30/2022]
Abstract
Background There is suggestive evidence that increased intake of dietary fibre and the use of non-steroidal anti-inflammatory drugs (NSAIDs) are generally associated with decreased colorectal cancer risk. However, the effects on precursors of colorectal cancer, such as adenomatous polyps, are mixed. We present the associations between dietary fibre intake and NSAID use on the presence and type of colorectal polyps in a screening population. Methods A cross-sectional study of 2548 individuals undergoing colonoscopy at the Forzani & MacPhail Colon Cancer Screening Centre (Calgary, Canada) was conducted. Dietary fibre intake and NSAID use were assessed using the Diet History Questionnaire I or II and the Health and Lifestyle Questionnaire. Colorectal outcomes were documented as a polyp or high-risk adenomatous polyp (HRAP; villous histology, high-grade dysplasia, ≥10 mm or ≥3 adenomas). Crude and ORs and 95% CIs were estimated using unconditional logistic regression. Results There were 1450 negative colonoscopies and 1098 patients with polyps, of which 189 patients had HRAPs. Total dietary fibre intake was associated with a decreased presence of HRAPs (OR=0.50, 95% CI: 0.29 to 0.86) when comparing the highest to lowest quartiles and was observed with both soluble (OR=0.51, 95% CI: 0.30 to 0.88) and insoluble (OR=0.51, 95% CI: 0.30 to 0.86) fibres. Ever use of NSAIDs was also inversely associated with HRAPs (OR=0.65, 95% CI: 0.47 to 0.89), observed with monthly (OR=0.60, 95% CI: 0.37 to 0.95) and daily (OR=0.53, 95% CI: 0.32 to 0.86) use. Conclusions Dietary fibre intake and NSAID use were associated with a decreased risk of having a HRAP at screening.
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Affiliation(s)
- Eileen Shaw
- Department of Cancer Epidemiology and Prevention Research, CancerControl Alberta, Alberta Health Services, Calgary, Alberta, Canada
| | - Matthew T Warkentin
- Department of Cancer Epidemiology and Prevention Research, CancerControl Alberta, Alberta Health Services, Calgary, Alberta, Canada
| | - S Elizabeth McGregor
- Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.,Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.,Population, Public and Indigenous Health, Alberta Health Services, Calgary, Alberta, Canada
| | - Susanna Town
- Forzani and MacPhail Colon Cancer Screening Centre, Alberta Health Services, Calgary, Alberta, Canada
| | - Robert J Hilsden
- Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.,Forzani and MacPhail Colon Cancer Screening Centre, Alberta Health Services, Calgary, Alberta, Canada
| | - Darren R Brenner
- Department of Cancer Epidemiology and Prevention Research, CancerControl Alberta, Alberta Health Services, Calgary, Alberta, Canada.,Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.,Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
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Veettil SK, Ching SM, Lim KG, Saokaew S, Phisalprapa P, Chaiyakunapruk N. Effects of calcium on the incidence of recurrent colorectal adenomas: A systematic review with meta-analysis and trial sequential analysis of randomized controlled trials. Medicine (Baltimore) 2017; 96:e7661. [PMID: 28796047 PMCID: PMC5556213 DOI: 10.1097/md.0000000000007661] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2016] [Revised: 06/05/2017] [Accepted: 07/07/2017] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND Protective effects of calcium supplementation against colorectal adenomas have been documented in systematic reviews; however, the results have not been conclusive. Our objective was to update and systematically evaluate the evidence for calcium supplementation taking into consideration the risks of systematic and random error and to GRADE the evidence. METHODS The study comprised a systematic review with meta-analysis and trial sequential analysis (TSA) of randomized controlled trials (RCTs). We searched for RCTs published up until September 2016. Retrieved trials were evaluated using risk of bias. Primary outcome measures were the incidences of any recurrent adenomas and of advanced adenomas. Meta-analytic estimates were calculated with the random-effects model and random errors were evaluated with trial sequential analyses (TSAs). RESULTS Five randomized trials (2234 patients with a history of adenomas) were included. Two of the 5 trials showed either unclear or high risks of bias in most criteria. Meta-analysis of good quality RCTs suggest a moderate protective effect of calcium supplementation on recurrence of adenomas (relative risk [RR], 0.88 [95% CI 0.79-0.99]); however, its effects on advanced adenomas did not show statistical significance (RR, 1.02 [95% CI 0.67-1.55]). Subgroup analyses demonstrated a greater protective effect on recurrence of adenomas with elemental calcium dose ≥1600 mg/day (RR, 0.74 [95% CI 0.56-0.97]) compared to ≤1200 mg/day (RR, 0.84 [95% CI 0.73-0.97]). No major serious adverse events were associated with the use of calcium, but there was an increase in the incidence of hypercalcemia (P = .0095). TSA indicated a lack of firm evidence for a beneficial effect. Concerns with directness and imprecision rated down the quality of the evidence to "low." CONCLUSION The available good quality RCTs suggests a possible beneficial effect of calcium supplementation on the recurrence of adenomas; however, TSA indicated that the accumulated evidence is still inconclusive. Using GRADE-methodology, we conclude that the quality of evidence is low. Large well-designed randomized trials with low risk of bias are needed.
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Affiliation(s)
- Sajesh K. Veettil
- School of Pharmacy/School of Postgraduate Studies, International Medical University, Kuala Lumpur
| | - Siew Mooi Ching
- Department of Family Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia
- Malaysian Research Institute on Ageing, Universiti Putra Malaysia, Serdang, Malaysia
| | - Kean Ghee Lim
- Clinical School, Department of Surgery, International Medical University, Seremban, Negeri Sembilan, Malaysia
| | - Surasak Saokaew
- Center of Health Outcomes Research and Therapeutic Safety (Cohorts), School of Pharmaceutical Sciences, University of Phayao, Thailand
- School of Pharmacy, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia
- Center of Pharmaceutical Outcomes Research, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok
- Unit of Excellence on Herbal Medicine, School of Pharmaceutical Sciences, University of Phayao
| | - Pochamana Phisalprapa
- Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Nathorn Chaiyakunapruk
- School of Pharmacy, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia
- Center of Pharmaceutical Outcomes Research, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok
- School of Pharmacy, University of Wisconsin, Madison, USA
- Asian Centre for Evidence Synthesis in Population, Implementation and Clinical Outcomes (PICO), Health and Well-being Cluster, Global Asia in the 21st Century (GA21) Platform, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia
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Zhao J, Zhu X, Shrubsole MJ, Ness RM, Hibler EA, Cai Q, Long J, Chen Z, Jiang M, Kabagambe EK, Zhang B, Hou L, Smalley WE, Edwards TL, Giovannucci EL, Zheng W, Dai Q. Interactions between calcium intake and polymorphisms in genes essential for calcium reabsorption and risk of colorectal neoplasia in a two-phase study. Mol Carcinog 2017; 56:2258-2266. [PMID: 28544176 DOI: 10.1002/mc.22678] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2016] [Revised: 05/09/2017] [Accepted: 05/19/2017] [Indexed: 12/31/2022]
Abstract
The SLC8A1 (solute carrier family 8, member 1) gene, encoding Na+ /Ca2+ exchanger, is essential in regulating calcium reabsorption and homeostasis. Calcium homeostasis plays a key role in cell proliferation and apoptosis. We hypothesized that polymorphisms in five calcium-regulating genes (SLC8A1, ATP2B1, CALB1, CALB2, and CABP1) interact with calcium intake in relation to the risk of colorectal neoplasia. A two-phase (discovery and replication) study was conducted within the Tennessee Colorectal Polyp Study, including a total of 1275 cases and 2811 controls. In Phase I, we identified six out of 135 SNPs that significantly interacted with calcium intake in relation to adenoma risk. In Phase II, the calcium intake by rs4952490 (SLC8A1) interaction was replicated (Pinteraction = 0.048). We found an inverse association between calcium intake (1000-2000 mg/day) and colorectal adenomas, particularly for multiple/advanced adenomas, among the G-allele carriers but not among homozygous carriers of the common variant (A) in rs4952490. In the joint analysis of SLC8A1, KCNJ1, and SLC12A1 SNPs, carriers of variant alleles in at least two genes and with calcium intake above the DRI (1000 mg/day) were approximately 30-57% less likely to have adenomas than those whose calcium intake was below the DRI. The association was stronger for multiple/advanced adenomas. No association was found among those who did not carry any variant alleles in these genes when calcium intake was below 2500 mg/day. These findings, if confirmed, may provide a new avenue for the personalized prevention of colorectal adenoma and cancer.
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Affiliation(s)
- Jing Zhao
- Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee.,Department of Veterans Affairs, Tennessee Valley Healthcare System, Geriatric, Research, Education and Clinical Center (GRECC), Nashville, Tennessee
| | - Xiangzhu Zhu
- Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee.,Department of Veterans Affairs, Tennessee Valley Healthcare System, Geriatric, Research, Education and Clinical Center (GRECC), Nashville, Tennessee
| | - Martha J Shrubsole
- Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee.,Department of Veterans Affairs, Tennessee Valley Healthcare System, Geriatric, Research, Education and Clinical Center (GRECC), Nashville, Tennessee.,Department of Medicine, Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Reid M Ness
- Department of Medicine, Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee.,Division of Gastroenterology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Elizabeth A Hibler
- Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Qiuyin Cai
- Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Jirong Long
- Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Zhi Chen
- Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Ming Jiang
- Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee.,Laboratory of Nuclear Receptors and Cancer Research, Center for Basic Medical Research, School of Medicine, Nantong University, Jiangsu, China
| | - Edmond K Kabagambe
- Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Bing Zhang
- Division of Gastroenterology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee.,Department of Biomedical Informatics, Vanderbilt University, Nashville, Tennessee
| | - Lifang Hou
- Department of Preventive Medicine, Northwestern University, Chicago, Illinois
| | - Walter E Smalley
- Department of Veterans Affairs, Tennessee Valley Healthcare System, Geriatric, Research, Education and Clinical Center (GRECC), Nashville, Tennessee.,Division of Gastroenterology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Todd L Edwards
- Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee.,Department of Veterans Affairs, Tennessee Valley Healthcare System, Geriatric, Research, Education and Clinical Center (GRECC), Nashville, Tennessee
| | - Edward L Giovannucci
- Department of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts
| | - Wei Zheng
- Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee.,Department of Veterans Affairs, Tennessee Valley Healthcare System, Geriatric, Research, Education and Clinical Center (GRECC), Nashville, Tennessee.,Department of Medicine, Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Qi Dai
- Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee.,Department of Veterans Affairs, Tennessee Valley Healthcare System, Geriatric, Research, Education and Clinical Center (GRECC), Nashville, Tennessee.,Department of Medicine, Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee
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Um CY, Fedirko V, Flanders WD, Höflich C, Wirthgen E, Bostick RM. Circulating insulin-like growth factor-related biomarkers: Correlates and responses to calcium supplementation in colorectal adenoma patients. Mol Carcinog 2017; 56:2127-2134. [PMID: 28467661 DOI: 10.1002/mc.22669] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2016] [Revised: 04/24/2017] [Accepted: 05/01/2017] [Indexed: 01/09/2023]
Abstract
Circulating insulin-like growth factor 1 (IGF-1) may be directly associated with colorectal cancer risk, and IGF binding protein 3 (IGFBP-3) is one of the most abundantly expressed binding proteins in various cancers. Calcium intakes, primarily from food, have been directly associated with circulating IGF-1, but whether supplemental calcium affects IGF-1 and IGFBP-3 is unknown. We tested the effects of 1.0 and 2.0 g of supplemental elemental calcium daily on circulating IGF-1 and IGFBP-3 concentrations in colorectal adenoma patients in a randomized, double-blinded, placebo-controlled clinical trial (n = 193). IGF-1 and IGFBP-3 were quantified using enzyme-linked immunoassay and quantitative Western ligand blot, respectively. We also assessed cross-sectional associations of these biomarkers with participants' baseline characteristics. We found no appreciable effect of calcium relative to placebo on circulating IGF-1, IGFBP-3, or the IGF-1:IGFBP-3 molar ratio. Mean IGF-1 concentrations were 11.1% higher in those with greater milk intakes (P = 0.05). Mean IGF-1 and IGFBP-3 concentrations were, respectively, 18.0% (P = 0.003) and 16.5% (P = 0.01) higher in men and were monotonically lower with increasing age (both P = 0.01). IGFBP-3 was 17.7% higher among those with higher relative to no alcohol consumption (P = 0.04). While these results support previous findings that IGF-1 concentrations are higher with greater milk intakes, and IGF-1 and IGFBP-3 concentrations differ according to sex and age, they provide no evidence to suggest that supplemental calcium appreciably affects circulating IGF-1, IGFBP-3, or the IGF-1:IGFBP-3 molar ratio in sporadic colorectal adenoma patients.
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Affiliation(s)
- Caroline Y Um
- Nutrition and Health Sciences Program, Emory University, Atlanta, Georgia
| | - Veronika Fedirko
- Nutrition and Health Sciences Program, Emory University, Atlanta, Georgia.,Department of Epidemiology,, Emory University, Atlanta, Georgia.,Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - W Dana Flanders
- Department of Epidemiology,, Emory University, Atlanta, Georgia.,Winship Cancer Institute, Emory University, Atlanta, Georgia
| | | | - Elisa Wirthgen
- Ligandis GbR, Gülzow, Germany.,Institute of Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany
| | - Roberd M Bostick
- Nutrition and Health Sciences Program, Emory University, Atlanta, Georgia.,Department of Epidemiology,, Emory University, Atlanta, Georgia.,Winship Cancer Institute, Emory University, Atlanta, Georgia
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Veettil SK, Teerawattanapong N, Ching SM, Lim KG, Saokaew S, Phisalprapa P, Chaiyakunapruk N. Effects of chemopreventive agents on the incidence of recurrent colorectal adenomas: a systematic review with network meta-analysis of randomized controlled trials. Onco Targets Ther 2017; 10:2689-2700. [PMID: 28579807 PMCID: PMC5449107 DOI: 10.2147/ott.s127335] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Protective effects of several chemopreventive agents (CPAs) against colorectal adenomas have been well documented in randomized controlled trials (RCTs); however, there is uncertainty regarding which agents are the most effective. METHODS We searched for RCTs published up until September 2016. Retrieved trials were evaluated using risk of bias. We performed both pairwise analysis and network meta-analysis (NMA) of RCTs to compare the effects of CPAs on the recurrence of colorectal adenomas (primary outcome). Using NMA, we ranked CPAs based on efficacy. RESULTS We identified 20 eligible RCTs enrolling 12,625 participants with a history of colorectal cancer or adenomas who were randomly assigned to receive either a placebo or one of 12 interventions. NMA using all trials demonstrated that celecoxib 800 mg/day (relative risk [RR] 0.61, 95% confidence interval [CI] 0.45-0.83), celecoxib 400 mg/day (RR 0.70, 95% CI 0.55-0.87), low-dose aspirin (RR 0.75, 95% CI 0.59-0.96) and calcium (RR 0.81, 95% CI 0.69-0.96) were significantly associated with a reduction in the recurrence of any adenomas. NMA results were consistent with those from pairwise meta-analysis. The evidence indicated a high (celecoxib), moderate (low-dose aspirin) and low (calcium) Grading of Recommendations, Assessment, Development and Evaluation (GRADE) quality. NMA ranking showed that celecoxib 800 mg/day and celecoxib 400 mg/day were the best CPAs, followed by low-dose aspirin and calcium. Considering advanced adenoma recurrence, only celecoxib 800 mg/day and celecoxib 400 mg/day were demonstrated to have a protective effect (RR 0.37, 95% CI 0.27-0.52 vs RR 0.48, 95% CI 0.38-0.60, respectively). CONCLUSION The available evidence from NMA suggests that celecoxib is more effective in reducing the risk of recurrence of colorectal adenomas, followed by low-dose aspirin and calcium. Since cyclooxygenase-2 (COX-2) inhibitors (eg, celecoxib) are associated with important cardiovascular events and gastrointestinal harms, more attention is warranted toward CPAs with a favorable benefit-to-risk ratio, such as low-dose aspirin and calcium.
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Affiliation(s)
- Sajesh K Veettil
- School of Pharmacy/School of Postgraduate Studies, International Medical University, Kuala Lumpur, Malaysia
| | - Nattawat Teerawattanapong
- Division of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Ubon Ratchathani University, Ubon Ratchathani, Thailand
| | - Siew Mooi Ching
- Department of Family Medicine, Faculty of Medicine and Health Sciences
- Malaysian Research Institute on Ageing, Universiti Putra Malaysia, Serdang
| | - Kean Ghee Lim
- Clinical School, Department of Surgery, International Medical University, Seremban, Negeri Sembilan
| | - Surasak Saokaew
- Center of Health Outcomes Research and Therapeutic Safety (Cohorts), School of Pharmaceutical Sciences, University of Phayao, Phayao
- School of Pharmacy, Monash University Malaysia, Selangor, Malaysia
- Centre of Pharmaceutical Outcomes Research, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand
- Unit of Excellence on Herbal Medicine, School of Pharmaceutical Sciences, University of Phayao, Thailand
| | - Pochamana Phisalprapa
- Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok
| | - Nathorn Chaiyakunapruk
- School of Pharmacy, Monash University Malaysia, Selangor, Malaysia
- Centre of Pharmaceutical Outcomes Research, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand
- School of Pharmacy, University of Wisconsin, Madison, USA
- Health and Well-being Cluster, Global Asia Platform in the 21st Century (GA21) Platform, Monash University Malaysia, Selangor, Malaysia
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Katsidzira L, Gangaidzo I, Thomson S, Rusakaniko S, Matenga J, Ramesar R. The shifting epidemiology of colorectal cancer in sub-Saharan Africa. Lancet Gastroenterol Hepatol 2017; 2:377-383. [PMID: 28397702 DOI: 10.1016/s2468-1253(16)30183-2] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2016] [Revised: 11/04/2016] [Accepted: 11/07/2016] [Indexed: 02/07/2023]
Abstract
The perception that colorectal cancer is rare in sub-Saharan Africa is widely held; however, it is unclear whether this is due to poor epidemiological data or to lower disease rates. The quality of epidemiological data has somewhat improved, and there is an ongoing transition to western dietary and lifestyle practices associated with colorectal cancer. The impact of these changes on the incidence of colorectal cancer is not as evident as it is with other non-communicable diseases such as diabetes. In this Viewpoint, we discuss the epidemiology of colorectal cancer in sub-Saharan Africa. Colorectal cancer in this region frequently occurs at an early age, often with distinctive histological characteristics. We detail the crucial need for hypothesis-driven research on the risk factors for colorectal cancer in this population and identify key research gaps. Should colorectal cancer occur more frequently than assumed, then commensurate allocation of resources will be needed for diagnosis and treatment.
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Affiliation(s)
- Leolin Katsidzira
- Division of Gastroenterology, Department of Medicine, University of Cape Town, Cape Town, South Africa; Department of Medicine, College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe.
| | - Innocent Gangaidzo
- Department of Medicine, College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe
| | - Sandie Thomson
- Division of Gastroenterology, Department of Medicine, University of Cape Town, Cape Town, South Africa
| | - Simbarashe Rusakaniko
- Department of Community Medicine, College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe
| | - Jonathan Matenga
- Department of Medicine, College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe
| | - Raj Ramesar
- MRC/UCT Human Genetics Research Unit, Division of Human Genetics, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
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Yao Y, Suo T, Andersson R, Cao Y, Wang C, Lu J, Chui E, Cochrane Colorectal Cancer Group. Dietary fibre for the prevention of recurrent colorectal adenomas and carcinomas. Cochrane Database Syst Rev 2017; 1:CD003430. [PMID: 28064440 PMCID: PMC6465195 DOI: 10.1002/14651858.cd003430.pub2] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND This is an update of the Cochrane review published in 2002.Colorectal cancer (CRC) is a major cause of morbidity and mortality in industrialised countries. Experimental evidence has supported the hypothesis that dietary fibre may protect against the development of CRC, although epidemiologic data have been inconclusive. OBJECTIVES To assess the effect of dietary fibre on the recurrence of colorectal adenomatous polyps in people with a known history of adenomatous polyps and on the incidence of CRC compared to placebo. Further, to identify the reported incidence of adverse effects, such as abdominal pain or diarrhoea, that resulted from the fibre intervention. SEARCH METHODS We identified randomised controlled trials (RCTs) from Cochrane Colorectal Cancer's Specialised Register, CENTRAL, MEDLINE and Embase (search date, 4 April 2016). We also searched ClinicalTrials.gov and WHO International Trials Registry Platform on October 2016. SELECTION CRITERIA We included RCTs or quasi-RCTs. The population were those having a history of adenomatous polyps, but no previous history of CRC, and repeated visualisation of the colon/rectum after at least two-years' follow-up. Dietary fibre was the intervention. The primary outcomes were the number of participants with: 1. at least one adenoma, 2. more than one adenoma, 3. at least one adenoma greater than or equal to 1 cm, or 4. a new diagnosis of CRC. The secondary outcome was the number of adverse events. DATA COLLECTION AND ANALYSIS Two reviewers independently extracted data, assessed trial quality and resolved discrepancies by consensus. We used risk ratios (RR) and risk difference (RD) with 95% confidence intervals (CI) to measure the effect. If statistical significance was reached, we reported the number needed to treat for an additional beneficial outcome (NNTB) or harmful outcome (NNTH). We combined the study data using the fixed-effect model if it was clinically, methodologically, and statistically reasonable. MAIN RESULTS We included seven studies, of which five studies with 4798 participants provided data for analyses in this review. The mean ages of the participants ranged from 56 to 66 years. All participants had a history of adenomas, which had been removed to achieve a polyp-free colon at baseline. The interventions were wheat bran fibre, ispaghula husk, or a comprehensive dietary intervention with high fibre whole food sources alone or in combination. The comparators were low-fibre (2 to 3 g per day), placebo, or a regular diet. The combined data showed no statistically significant difference between the intervention and control groups for the number of participants with at least one adenoma (5 RCTs, n = 3641, RR 1.04, 95% CI 0.95 to 1.13, low-quality evidence), more than one adenoma (2 RCTs, n = 2542, RR 1.06, 95% CI 0.94 to 1.20, low-quality evidence), or at least one adenoma 1 cm or greater (4 RCTs, n = 3224, RR 0.99, 95% CI 0.82 to 1.20, low-quality evidence) at three to four years. The results on the number of participants diagnosed with colorectal cancer favoured the control group over the dietary fibre group (2 RCTS, n = 2794, RR 2.70, 95% CI 1.07 to 6.85, low-quality evidence). After 8 years of comprehensive dietary intervention, no statistically significant difference was found in the number of participants with at least one recurrent adenoma (1 RCT, n = 1905, RR 0.97, 95% CI 0.78 to 1.20), or with more than one adenoma (1 RCT, n = 1905, RR 0.89, 95% CI 0.64 to 1.24). More participants given ispaghula husk group had at least one recurrent adenoma than the control group (1 RCT, n = 376, RR 1.45, 95% CI 1.01 to 2.08). Other analyses by types of fibre intervention were not statistically significant. The overall dropout rate was over 16% in these trials with no reasons given for these losses. Sensitivity analysis incorporating these missing data shows that none of the results can be considered as robust; when the large numbers of participants lost to follow-up were assumed to have had an event or not, the results changed sufficiently to alter the conclusions that we would draw. Therefore, the reliability of the findings may have been compromised by these missing data (attrition bias) and should be interpreted with caution. AUTHORS' CONCLUSIONS There is a lack of evidence from existing RCTs to suggest that increased dietary fibre intake will reduce the recurrence of adenomatous polyps in those with a history of adenomatous polyps within a two to eight year period. However, these results may be unreliable and should be interpreted cautiously, not only because of the high rate of loss to follow-up, but also because adenomatous polyp is a surrogate outcome for the unobserved true endpoint CRC. Longer-term trials with higher dietary fibre levels are needed to enable confident conclusion.
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Affiliation(s)
- Yibo Yao
- Longhua Hospital, Shanghai Traditional Chinese Medicine UniversityDepartment of Anorectal Surgery725 South Wanping Road, Xuhui DistrictShanghaiShanghaiChina200032
| | - Tao Suo
- Zhongshan Hospital, Fudan UniversityDepartment of General Surgery, Institute of General Surgery180 Fenglin Road, Xuhui DistrictShanghaiShanghaiChina200032
| | - Roland Andersson
- Faculty of Medicine, Lund UniversityDepartment of Surgery, Clinical SciencesLund University HospitalLundSwedenSE‐221 85
| | - Yongqing Cao
- Longhua Hospital, Shanghai Traditional Chinese Medicine UniversityDepartment of Anorectal Surgery725 South Wanping Road, Xuhui DistrictShanghaiShanghaiChina200032
| | - Chen Wang
- Longhua Hospital, Shanghai Traditional Chinese Medicine UniversityDepartment of Anorectal Surgery725 South Wanping Road, Xuhui DistrictShanghaiShanghaiChina200032
| | - Jingen Lu
- Longhua Hospital, Shanghai Traditional Chinese Medicine UniversityDepartment of Anorectal Surgery725 South Wanping Road, Xuhui DistrictShanghaiShanghaiChina200032
| | - Evelyne Chui
- Systematic Review Solutions Ltd5‐6 West Tashan RoadYan TaiChina264000
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Dulai PS, Singh S, Marquez E, Khera R, Prokop LJ, Limburg PJ, Gupta S, Murad MH. Chemoprevention of colorectal cancer in individuals with previous colorectal neoplasia: systematic review and network meta-analysis. BMJ 2016; 355:i6188. [PMID: 27919915 PMCID: PMC5137632 DOI: 10.1136/bmj.i6188] [Citation(s) in RCA: 57] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE To assess the comparative efficacy and safety of candidate agents (low and high dose aspirin, non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs), calcium, vitamin D, folic acid, alone or in combination) for prevention of advanced metachronous neoplasia (that is, occurring at different times after resection of initial neoplasia) in individuals with previous colorectal neoplasia, through a systematic review and network meta-analysis. DATA SOURCES Medline, Embase, Web of Science, from inception to 15 October 2015; clinical trial registries. STUDY SELECTION Randomized controlled trials in adults with previous colorectal neoplasia, treated with candidate chemoprevention agents, and compared with placebo or another candidate agent. Primary efficacy outcome was risk of advanced metachronous neoplasia; safety outcome was serious adverse events. DATA EXTRACTION Two investigators identified studies and abstracted data. A Bayesian network meta-analysis was performed and relative ranking of agents was assessed with surface under the cumulative ranking (SUCRA) probabilities (ranging from 1, indicating that the treatment has a high likelihood to be best, to 0, indicating the treatment has a high likelihood to be worst). Quality of evidence was appraised with GRADE criteria. RESULTS 15 randomized controlled trials (12 234 patients) comparing 10 different strategies were included. Compared with placebo, non-aspirin NSAIDs were ranked best for preventing advanced metachronous neoplasia (odds ratio 0.37, 95% credible interval 0.24 to 0.53; SUCRA=0.98; high quality evidence), followed by low-dose aspirin (0.71, 0.41 to 1.23; SUCRA=0.67; low quality evidence). Low dose aspirin, however, was ranked the safest among chemoprevention agents (0.78, 0.43 to 1.38; SUCRA=0.84), whereas non-aspirin NSAIDs (1.23, 0.95 to 1.64; SUCRA=0.26) were ranked low for safety. High dose aspirin was comparable with low dose aspirin in efficacy (1.12, 0.59 to 2.10; SUCRA=0.58) but had an inferior safety profile (SUCRA=0.51). Efficacy of agents for reducing metachronous colorectal cancer could not be estimated. CONCLUSIONS Among individuals with previous colorectal neoplasia, non-aspirin NSAIDs are the most effective agents for the prevention of advanced metachronous neoplasia, whereas low dose aspirin has the most favorable risk:benefit profile. REGISTRATION PROSPERO (CRD42015029598).
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Affiliation(s)
- Parambir S Dulai
- Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA
| | - Siddharth Singh
- Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA
- Division of Biomedical Informatics, University of California San Diego, La Jolla, CA, USA
| | - Evelyn Marquez
- Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA
| | - Rohan Khera
- Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Larry J Prokop
- Department of Library Services, Mayo Clinic, Rochester, MN, USA
| | - Paul J Limburg
- Divison of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Samir Gupta
- Veterans Affairs San Diego Healthcare System, San Diego, CA, USA
- Moores Cancer Center, University of San Diego, La Jolla, CA, USA
| | - Mohammad Hassan Murad
- Robert D and Patricia E Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA
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