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      Processed and Unprocessed Red Meat and Risk of Colorectal Cancer: Analysis by Tumor Location and Modification by Time

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          Abstract

          Although the association between red meat consumption and colorectal cancer (CRC) is well established, the association across subsites of the colon and rectum remains uncertain, as does time of consumption in relation to cancer development. As these relationships are key for understanding the pathogenesis of CRC, they were examined in two large cohorts with repeated dietary measures over time, the Nurses’ Health Study (n = 87,108 women, 1980–2010) and Health Professionals Follow-up Study (n = 47,389 men, 1986–2010). Cox proportional hazards regression models generated hazard ratios (HRs) and 95% confidence intervals (CIs), which were pooled by random-effects meta-analysis. In combined cohorts, there were 2,731 CRC cases (1,151 proximal colon, 816 distal colon, and 589 rectum). In pooled analyses, processed red meat was positively associated with CRC risk (per 1 serving/day increase: HR = 1.15, 95% CI: 1.01–1.32; P for trend 0.03) and particularly with distal colon cancer (per 1 serving/day increase; HR = 1.36; 95% CI: 1.09–1.69; P for trend 0.006). Recent consumption of processed meat (within the past 4 years) was not associated with distal cancer. Unprocessed red meat was inversely associated with risk of distal colon cancer and a weak non-significant positive association between unprocessed red meat and proximal cancer was observed (per 1 serving/day increase: distal HR = 0.75; 95% CI: 0.68–0.82; P for trend <0.001; proximal HR = 1.14, 95% CI: 0.92–1.40; P for trend 0.22). Thus, in these two large cohorts of US health professionals, processed meat intake was positively associated with risk of CRC, particularly distal cancer, with little evidence that higher intake of unprocessed red meat substantially increased risk of CRC. Future studies, particularly those with sufficient sample size to assess associations by subsites across the colon are needed to confirm these findings and elucidate potentially distinct mechanisms underlying the relationship between processed meat and subtypes of unprocessed red meat with CRC.

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          Most cited references37

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          Applying Cox regression to competing risks.

          Two methods are given for the joint estimation of parameters in models for competing risks in survival analysis. In both cases Cox's proportional hazards regression model is fitted using a data duplication method. In principle either method can be used for any number of different failure types, assuming independent risks. Advantages of the augmented data approach are that it limits over-parametrisation and it runs immediately on existing software. The methods are used to reanalyse data from two well-known published studies, providing new insights.
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            The impact of dietary and lifestyle risk factors on risk of colorectal cancer: a quantitative overview of the epidemiological evidence.

            Colorectal cancer is a major cause of cancer mortality and is considered to be largely attributable to inappropriate lifestyle and behavior patterns. The purpose of this review was to undertake a comparison of the strength of the associations between known and putative risk factors for colorectal cancer by conducting 10 independent meta-analyses of prospective cohort studies. Studies published between 1966 and January 2008 were identified through EMBASE and MEDLINE, using a combined text word and MESH heading search strategy. Studies were eligible if they reported estimates of the relative risk for colorectal cancer with any of the following: alcohol, smoking, diabetes, physical activity, meat, fish, poultry, fruits and vegetables. Studies were excluded if the estimates were not adjusted at least for age. Overall, data from 103 cohort studies were included. The risk of colorectal cancer was significantly associated with alcohol: individuals consuming the most alcohol had 60% greater risk of colorectal cancer compared with non- or light drinkers (relative risk 1.56, 95% CI 1.42-1.70). Smoking, diabetes, obesity and high meat intakes were each associated with a significant 20% increased risk of colorectal cancer (compared with individuals in the lowest categories for each) with little evidence of between-study heterogeneity or publication bias. Physical activity was protective against colorectal cancer. Public-health strategies that promote modest alcohol consumption, smoking cessation, weight loss, increased physical activity and moderate consumption of red and processed meat are likely to have significant benefits at the population level for reducing the incidence of colorectal cancer.
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              Meat, fish, and colorectal cancer risk: the European Prospective Investigation into cancer and nutrition.

              Current evidence suggests that high red meat intake is associated with increased colorectal cancer risk. High fish intake may be associated with a decreased risk, but the existing evidence is less convincing. We prospectively followed 478 040 men and women from 10 European countries who were free of cancer at enrollment between 1992 and 1998. Information on diet and lifestyle was collected at baseline. After a mean follow-up of 4.8 years, 1329 incident colorectal cancers were documented. We examined the relationship between intakes of red and processed meat, poultry, and fish and colorectal cancer risk using a proportional hazards model adjusted for age, sex, energy (nonfat and fat sources), height, weight, work-related physical activity, smoking status, dietary fiber and folate, and alcohol consumption, stratified by center. A calibration substudy based on 36 994 subjects was used to correct hazard ratios (HRs) and 95% confidence intervals (CIs) for diet measurement errors. All statistical tests were two-sided. Colorectal cancer risk was positively associated with intake of red and processed meat (highest [>160 g/day] versus lowest [ 80 g/day versus <10 g/day, HR = 0.69, 95 % CI = 0.54 to 0.88; Ptrend<.001), but was not related to poultry intake. Correcting for measurement error strengthened the associations between colorectal cancer and red and processed meat intake (per 100-g increase HR = 1.25, 95% CI =1.09 to 1.41, Ptrend = .001 and HR = 1.55, 95% CI = 1.19 to 2.02, Ptrend = .001 before and after calibration, respectively) and for fish (per 100 g increase HR = 0.70, 95% CI = 0.57 to 0.87, Ptrend<.001 and HR = 0.46, 95% CI = 0.27 to 0.77, Ptrend = .003; before and after correction, respectively). In this study population, the absolute risk of development of colorectal cancer within 10 years for a study subject aged 50 years was 1.71% for the highest category of red and processed meat intake and 1.28% for the lowest category of intake and was 1.86% for subjects in the lowest category of fish intake and 1.28% for subjects in the highest category of fish intake. Our data confirm that colorectal cancer risk is positively associated with high consumption of red and processed meat and support an inverse association with fish intake.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                25 August 2015
                2015
                : 10
                : 8
                : e0135959
                Affiliations
                [1 ]Rally Health, San Francisco, California, United States of America
                [2 ]Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America
                [3 ]Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America
                [4 ]Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China
                [5 ]Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America
                [6 ]Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America
                [7 ]Hanoi Medical University, Hanoi, Vietnam
                [8 ]Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, United States of America
                [9 ]Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, United States of America
                [10 ]Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, United States of America
                Tufts University, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: AB MS EG CF AC SO WW KW. Performed the experiments: AB MS XZ AP. Analyzed the data: AB MS XZ MW NL KW. Contributed reagents/materials/analysis tools: MW. Wrote the paper: AB MS XZ AP MW EG SO CF NL AC WW KW. Collected data: CF AC EG.

                Article
                PONE-D-15-08857
                10.1371/journal.pone.0135959
                4549221
                26305323
                50d1ac92-d425-475a-9cbc-640c04a02ad3
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 27 February 2015
                : 28 July 2015
                Page count
                Figures: 0, Tables: 3, Pages: 16
                Funding
                This research was funded by the following federal grants: P01 CA87969, UM1 CA167552, P01 CA 55075, P01 CA055075, UM1 CA167552, UM1 CA186107, and P01 CA87969. In addition, funding came from the Entertainment Industry Foundation's National Colorectal Cancer Research Alliance (NCCRA). This work was also supported by a UICC American Cancer Society Beginning Investigator Fellowship (Dr. Ngoan Le), funded by the American Cancer Society. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Custom metadata
                Data are from the Nurses’ Health Study and Health Professionals Follow-up Study, whose authors may be contacted at nhspermission@ 123456channing.harvard.edu . Procedures to obtain access are described at http://www.channing.harvard.edu/nhs/?page_id=471.

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