News Release

Red meat intake, poor education linked to colorectal cancer

Peer-Reviewed Publication

Oxford University Press USA

A new paper in JNCI Cancer Spectrum, published by Oxford University Press, indicates that several non-genetic factors--including greater red meat intake, lower educational attainment, and heavier alcohol use--are associated with an increase in colorectal cancer in people under 50.

In the United States, incidence rates of early-onset colorectal cancer have nearly doubled between 1992 and 2013 (from 8.6 to 13.1 per 100,000), with most of this increase due to early-onset cancers of the rectum. Approximately 1 in 10 diagnoses of colorectal cancer in this country occur in people under 50.

Researchers have observed the rise particularly among people born since the 1960s in studies from the United States, Canada, Australia, and Japan. During the same period there have been major changes in diets among younger generations across the developing world. Such changes include decreases in consumption of fruits, non-potato vegetables, and calcium-rich dairy sources. This is coupled with an increase in processed foods (e.g., meats, pizza, macaroni and cheese, etc.) and soft drinks. Average nutrient intakes of fiber, folate, and calcium among the U.S. population are also lower than recommended.

The increase in early onset colorectal cancer is concerning to researchers because these cancers often have worse outcomes than those diagnosed in older people. It has led to recommendations that colorectal cancer screening begin at younger ages.

Previous research has outlined potential risk factors for early-onset colorectal cancer including greater consumption of processed meat, reduced consumption of vegetables and citrus fruit, greater body mass index, sedentary lifestyles, greater alcohol use, smoking, reduced aspirin use, and diabetes. However, researchers have yet to perform a comprehensive, large-scale evaluation that compares the magnitude of these risks with those for late-onset colorectal cancer and assesses whether the risks for early-onset colorectal cancer correlate with specific types of colorectal cancer.

Using data pooled from 13 population-based studies, researchers here studied 3,767 colorectal cancer cases and 4,049 controls in people under 50 and 23,437 colorectal cancer cases and 35,311 controls in people 50 or above years.

Early-onset colorectal cancer was associated with not regularly using aspirins, greater red meat intake, lower educational attainment, heavier alcohol use, and (interestingly enough) also alcohol abstinence. Researchers also found that lower total fiber intake was linked more strongly to rectal than colon cancer.

Several other colorectal cancer risk factors trended toward an association with early-onset colorectal cancer, including history of diabetes and lower folate, dietary fiber, and calcium intake. However, neither BMI nor smoking were risk factors in the early-onset group, in contrast to the late-onset group.

According to Richard Hayes, the senior investigator for this research: "this first large-scale study of non-genetic risk factors for early-onset colorectal cancer is providing the initial basis for targeted identification of those most at risk, which is imperative in mitigating the rising burden of this disease."


Direct correspondence to:

Richard B. Hayes
Professor of Population Health and Environmental Medicine
NYU Langone Health
180 Madison Ave, Room 415
New York, NY 10016

To request a copy of the study, please contact:

Daniel Luzer

This work was funded by the National Cancer Institute under R03-CA215775-02, awarded to Dr Richard Hayes, and through the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) funded by the National Cancer Institute, National Institutes of Health, US Department of Health and Human Services (U01 CA164930, R01 CA201407), awarded to Dr Ulrike Peters. This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA015704 and training grant T32HS026120, from the Agency for Healthcare Research and Quality. The Colon Cancer Family Registry (CCFR, is supported in part by funding from the National Cancer Institute (NCI), National Institutes of Health (NIH) (award U01 CA167551). The CCFR Set-1 (Illumina 1M/1M-Duo) and Set-2 (Illumina Omni1-Quad) scans were supported by NIH awards U01 CA122839 and R01 CA143247 (to GC). The CCFR Set-3 (Affymetrix Axiom CORECT Set array) was supported by NIH award U19 CA148107 and R01 CA81488 (to SBG). The CCFR Set-4 (Illumina OncoArray 600K SNP array) was supported by NIH award U19 CA148107 (to SBG) and by the Center for Table 3. Association between anthropometric, dietary, lifestyle, and pharmacological risk factors and early-onset colorectal cancer risk, strati?ed by anatomic subsite

Lifestyle and environmental risk factora

Colon cancerb Rectal cancerb

Colon vs rectumc OR (95% CI) P OR (95% CI) PP

Anthropometric BMI, per 5kg/m2 1.05 (0.99 to 1.10) .09 0.99 (0.93 to 1.06) .84 .11 Height, per 10cm 1.03 (0.94 to 1.12) .55 1.03 (0.93 to 1.13) .57 .96 Lifestyle Pack-years of smoking 0.99 (0.94 to 1.04) .69 0.99 (0.94 to 1.05) .73 .99 Sedentary lifestyle 1.15 (0.88 to 1.51) .30 1.09 (0.78 to 1.53) .63 .77 Alcohol use, 0g/d 1.28 (1.12 to 1.47) <.001 1.30 (1.11 to 1.53) .001 .86 Alcohol use, >28g/d 1.29 (1.06 to 1.57) .01 1.34 (1.08 to 1.67) .009 .75 Lower educational attainment, highest level completed 1.12 (1.05 to 1.18) <.001 1.13 (1.06 to 1.21) <.001 .68 History of diabetes 1.20 (0.88 to 1.63) .25 1.28 (0.90 to 1.81) .16 .70 Dietary Lower total folate intake, mcg/dd 1.14 (1.04 to 1.24) .003 1.24 (1.11 to 1.37) <.001 .12 Lower fruit intake, servings/dd 1.05 (0.99 to 1.10) .09 1.10 (1.03 to 1.17) .004 .16 Lower vegetable intake, servings/dd 1.03 (0.97 to 1.10) .28 1.08 (1.01 to 1.16) .03 .24 Greater red meat intake, servings/dd 1.12 (1.06 to 1.18) <.001 1.12 (1.05 to 1.19) .001 .99 Greater processed meat intake (servings/day)d 1.06 (0.97 to 1.16) .18 1.09 (0.98 to 1.21) .11 .65 Lower total ?ber intake, g/dd 1.14 (1.02 to 1.27) .02 1.30 (1.14 to 1.48) <.001 .04 Lower total calcium intake, mg/dd 1.15 (1.05 to 1.26) .003 1.24 (1.11 to 1.39) <.001 .18 Pharmacological No aspirin use 1.15 (0.92 to 1.42) .21 1.04 (0.81 to 1.34) .75 .47 No NSAID use 1.33 (1.12 to 1.60) .002 1.66 (1.31 to 2.09) <.001 .08

aThe referent category for each categorical factor was de?ned as the following: presence of a sedentary lifestyle (no), alcohol intake (1-28g/d), educational attainment (collegegraduate), history of diabetes (no), aspirinuse (yes), andNSAID use (yes). BMI¼body massindex; CI¼con?dence interval; NSAID¼nonsteroidal anti-in?ammatory drug; OR¼odds ratio. bMultinomial logistic regression models include individual nongenetic factors and were adjusted for age, sex, study, family history, and total energy consumption (for dietary factors). cv2 test for contrasts in multinomial models. dDietary variables were harmonized across studies by sex- and study-speci?c quartiles and assigned values 0, 1, 2, and 3 in the order of increasing risk. These variables were treated as continuous variables in the analysis.

A. N. Archambault et al. | 7 of 10

Inherited Disease Research (CIDR), which is funded by the NIH to the Johns Hopkins University, contract number HHSN268201200008I. CRCGEN: Colorectal Cancer Genetics & Genomics, Spanish study was supported by Instituto de Salud Carlos III, co-funded by FEDER funds -a way to build Europe- (grants PI14-613 and PI09-1286), Agency for Management of University and Research Grants (AGAUR) of the Catalan Government (grant 2017SGR723), and Junta de Castilla y Leon (grant LE22A10-2). Sample collection of this work was supported by the Xarxa de Bancs de Tumors de Catalunya sponsored by Pla Director d'Oncolog?a de Catalunya (XBTC), Plataforma Biobancos PT13/0010/0013 and ICOBIOBANC, sponsored by the Catalan Institute of Oncology. DACHS: This work was supported by the German Research Council (BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1, HO 5117/2-1, HE 5998/2-1, KL 2354/3-1, RO 2270/8-1 and BR 1704/17-1), the Interdisciplinary Research Program of the National Center for Tumor Diseases (NCT), Germany, and the German Federal Ministry of Education and Research (01KH0404, 01ER0814, 01ER0815, 01ER1505A and 01ER1505B). DALS: National Institutes of Health (R01 CA48998 to M. L. Slattery). EPIC: The coordination of EPIC is financially supported by the European Commission (DGSANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRCItaly and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Ska?ne and V€asterbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPICNorfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom). Kentucky: This work was supported by the following grant support: Clinical Investigator Award from Damon Runyon Cancer Research Foundation (CI-8); NCI R01CA136726. LCCS: The Leeds Colorectal Cancer Study was funded by the Food Standards Agency and Cancer Research UK Programme Award (C588/A19167). MECC: This work was supported by the National Institutes of Health, U.S. Department of Health and Human Services (R01 CA81488 to SBG and GR). NCCCS I & II: We acknowledge funding support for this project from the National Institutes of Health, R01 CA66635 and P30 DK034987. NFCCR: This work was supported by an

Interdisciplinary Health Research Team award from the Canadian Institutes of Health Research (CRT 43821); the National Institutes of Health, U.S. Department of Health and Human Services (U01 CA74783); and National Cancer Institute of Canada grants (18223 and 18226). The authors wish to acknowledge the contribution of Alexandre Belisle and the genotyping team of the McGill University and Genome Quebec Innovation Centre, Montreal, Canada, for genotyping the Sequenom panel in the NFCCR samples. Funding was provided to Michael O. Woods by the Canadian Cancer Society Research Institute. Harvard cohort (NHS): NHS is supported by the National Institutes of Health (R01 CA137178, P01 CA087969, UM1 CA186107, R01 CA151993, R35 CA197735, K07CA190673, and P50 CA127003). OFCCR: The Ontario Familial Colorectal Cancer Registry was supported in part by the National Cancer Institute (NCI) of the National Institutes of Health (NIH) under award U01 CA167551 and award U01/U24 CA074783 (to SG). Additional funding for the OFCCR and ARCTIC testing and genetic analysis was through and a Canadian Cancer Society CaRE (Cancer Risk Evaluation) program grant and Ontario Research Fund award GL201-043 (to BWZ), through the Canadian Institutes of Health Research award 112746 (to TJH), and through generous support from the Ontario Ministry of Research and Innovation. SCCFR: The Seattle Colon Cancer Family Registry was supported in part by the National Cancer Institute (NCI) of the National Institutes of Health (NIH) under awards U01 CA167551, U01 CA074794 (to JDP), and awards U24 CA074794 and R01 CA076366 (to PAN). UK Biobank: This research has been conducted using the UK Biobank Resource under Application Number 8614.

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