Study2024

Genome-Wide Gene-Environment Interaction Analyses to Understand the Relationship between Red Meat and Processed Meat Intake and Colorectal Cancer Risk

Stern MC, Sanchez Mendez J, Kim AE, Obón-Santacana M, Moratalla-Navarro F, Martín V, Moreno V, Lin Y, Bien SA, Qu C, Su YR, White E, Harrison TA, Huyghe JR, Tangen CM, Newcomb PA, Phipps AI, Thomas CE, Kawaguchi ES, Lewinger JP, Morrison JL, Conti DV, Wang J, Thomas DC, Platz EA, Visvanathan K, Keku TO, Newton CC, Um CY, Kundaje A, Shcherbina A, Murphy N, Gunter MJ, Dimou N, Papadimitriou N, Bézieau S, van Duijnhoven FJB, Männistö S, Rennert G, Wolk A, Hoffmeister M, Brenner H, Chang-Claude J, Tian Y, Le Marchand L, Cotterchio M, Tsilidis KK, Bishop DT, Melaku YA, Lynch BM, Buchanan DD, Ulrich CM, Ose J, Peoples AR, Pellatt AJ, Li L, Devall MAM, Campbell PT, Albanes D, Weinstein SJ, Berndt SI, Gruber SB, Ruiz-Narvaez E, Song M, Joshi AD, Drew DA, Petrick JL, Chan AT, Giannakis M, Peters U, Hsu L, Gauderman WJ

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 14 citations

Review labels

Food frequency questionnaireNo stated lifestyle adjustment

Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.

How it was studied

Design: Case-control study (classified by our AI screen)
Studied in: People
Main outcome: Clinical events such as disease or death
Intake measured by: Food frequency questionnaire

Who paid for it

Funding: Possibly industry funded
Government: U.S. Department of Health and Human Services
Nonprofit: American Cancer Society
Nonprofit: Damon Runyon Cancer Research Foundation
Government: World Health Organization
University or hospital: Brigham and Women's Hospital
University or hospital: Fred Hutchinson Cancer Research Center
University or hospital: Emory University
Government: Division of Cancer Prevention, National Cancer Institute
Nonprofit: Association Anne de Bretagne Genetique
University or hospital: Johns Hopkins University
University or hospital: University of Pittsburgh
Government: Victorian Cancer Agency
University or hospital: Harvard T.H. Chan School of Public Health
Government: Center for Strategic Scientific Initiatives, National Cancer Institute
University or hospital: Deutsches Krebsforschungszentrum
University or hospital: Marshfield Clinic Research Foundation
Nonprofit: Swedish Cancer Foundation
Government: Centres de Recerca de Catalunya
Nonprofit: Cancer Research UK
Government: National Institute for Health and Care Research
Government: Food Standards Agency
University or hospital: Imperial College London
Government: Deutsche Forschungsgemeinschaft
Government: Institut National de la Santé et de la Recherche Médicale
Government: Bundesministerium für Bildung und Forschung
Nonprofit: Fundación Científica Asociación Española Contra el Cáncer
Nonprofit: Cancerfonden
Government: Generalitat de Catalunya
Government: Ministerio de Economía y Competitividad
Nonprofit: Ligue Contre le Cancer
Government: Vetenskapsrådet
Nonprofit: Associazione Italiana per la Ricerca sul Cancro
Nonprofit: Deutsche Krebshilfe
University or hospital: Institut Gustave-Roussy
Nonprofit: Mutuelle Générale de l'Education Nationale
University or hospital: Centre Hospitalier Universitaire de Nantes
Government: Conseil Régional des Pays de la Loire
Government: Junta de Castilla y León
University or hospital: Xarxa de Bancs de Tumors de Catalunya
Industry group: Groupement des Entreprises Françaises dans la lutte contre le Cancer
Government: National Institutes of Health
Government: Centers for Disease Control and Prevention
Government: Medical Research Council
Nonprofit: World Cancer Research Fund
Government: National Health and Medical Research Council
Nonprofit: Cancer Council Victoria
Government: Agència de Gestió d'Ajuts Universitaris i de Recerca
Government: Instituto de Salud Carlos III
University or hospital: NIHR Imperial Biomedical Research Centre
University or hospital: School of Public Health, Imperial College London
Government: National Institute on Aging
Government: National Heart, Lung, and Blood Institute
Government: National Human Genome Research Institute
Government: National Cancer Institute
Government: National Institute of Diabetes and Digestive and Kidney Diseases
Government: National Institute of Environmental Health Sciences
Government: Office of Research Infrastructure Programs, National Institutes of Health
Government: NHLBI NIH HHS
Government: NCI NIH HHS
Government: NIH HHS
Government: NIDDK NIH HHS
Government: NIA NIH HHS
Government: NHGRI NIH HHS
Government: Intramural NIH HHS
Government: Agència de Gestió d'Ajuts Universitaris i de Recerca
Government: NIEHS NIH HHS
Grants: National Institute of Environmental Health Sciences (P30-ES010126); National Cancer Institute (R01 CA048998); Cancer Council Victoria (MR/M012190/1); Fred Hutchinson Cancer Research Center (HHSN268201600001C); U.S. Department of Health and Human Services (HHSN268201600002 C); Vetenskapsrådet (14136); National Heart, Lung, and Blood Institute (P30CA014089); National Health and Medical Research Council (251553); National Cancer Institute (P30 CA014089); National Cancer Institute (R01-CA136726); National Cancer Institute (CA 087969); National Cancer Institute (U01 CA167552); National Cancer Institute (P30CA 006973); Medical Research Council (M012190/1); Damon Runyon Cancer Research Foundation (NCI R01CA136726); Mutuelle Générale de l'Education Nationale (MR/M012190/1); Fred Hutchinson Cancer Research Center (P30CA015704); National Cancer Institute (P01 CA055075.); Deutsche Forschungsgemeinschaft (BR 1704/6-3); National Cancer Institute (U01CA261339); Instituto de Salud Carlos III (PI09/1286); Ligue Contre le Cancer (209057); National Cancer Institute (CA-167552); American Cancer Society (R01 CA137178); Deutsche Forschungsgemeinschaft (BR 1704/17–1); Cancer Council Victoria (UM1 CA186107); National Institutes of Health (HHSN268201600018C); Medical Research Council (1000143 (to EPIC‐Norfolk)); U.S. Department of Health and Human Services (C8221); National Institute on Aging (U01 AG018033); Junta de Castilla y León (LE22A10‐2); National Cancer Institute (P30 CA 015704); National Cancer Institute (CA006973); Swedish Cancer Foundation (14136); Deutsche Krebshilfe (14136); Institut National de la Santé et de la Recherche Médicale (UM1 CA186107); National Heart, Lung, and Blood Institute (HHSN268201600018C); National Institutes of Health (5u19ca148107-04); National Cancer Institute (K05-CA154337); Vetenskapsrådet (UM1 CA186107); Bundesministerium für Bildung und Forschung (UM1 CA186107); World Cancer Research Fund (209057); National Cancer Institute (P01 CA087969); National Cancer Institute (U01 CA137088); National Cancer Institute (R01 CA81488); World Cancer Research Fund (14136); Cancer Council Victoria (1000143); Cancer Research UK (14136 to EPIC-Norfolk); Deutsche Forschungsgemeinschaft (HE 5998/2‐1); National Cancer Institute (CA037429); National Institutes of Health (1s10od028685-01); Generalitat de Catalunya (2017SGR723); Ligue Contre le Cancer (MR/M012190/1); U.S. Department of Health and Human Services (R01 CA81488); National Cancer Institute (R01CA143237); U.S. Department of Health and Human Services (HHSN268201600018 C); National Cancer Institute (UM1 CA186107); Bundesministerium für Bildung und Forschung (1000143); Deutsche Forschungsgemeinschaft (HO 5117/ 2-1); National Cancer Institute (HHSN268201600001C); National Cancer Institute (R01CA063464); Mutuelle Générale de l'Education Nationale (14136); National Cancer Institute (01ER0814); World Cancer Research Fund (MR/M012190/1); National Cancer Institute (R01CA059045.); National Cancer Institute (CA143237); National Cancer Institute (UM1 CA182883); U.S. Department of Health and Human Services (R01 CA201407); Bundesministerium für Bildung und Forschung (14136); National Cancer Institute (R37 CA054281); Agència de Gestió d'Ajuts Universitaris i de Recerca (2017SGR723); Institut Gustave-Roussy (MR/M012190/1); National Institutes of Health (7r01ca059045-02); National Cancer Institute (Z01 CP 010200); Institut National de la Santé et de la Recherche Médicale (209057); Bundesministerium für Bildung und Forschung (01ER1505B); Bundesministerium für Bildung und Forschung (01ER1505A); National Cancer Institute (CA151993); Ligue Contre le Cancer (UM1 CA186107); National Cancer Institute (01ER1505A); Deutsche Krebshilfe (MR/M012190/1); National Institute for Health and Care Research (209057); Deutsche Forschungsgemeinschaft (BR1704/6-1); National Cancer Institute (U19 CA148107); National Cancer Institute (CA197735); Center for Strategic Scientific Initiatives, National Cancer Institute (U01 CA167551); Medical Research Council (UM1 CA167552); Ligue Contre le Cancer (14136); Victorian Cancer Agency (209057); National Cancer Institute (CA201407); National Cancer Institute (UM1-CA-167552); National Cancer Institute (CA055075); National Cancer Institute (R01CA176272); National Heart, Lung, and Blood Institute (HHSN268201600004C); National Cancer Institute (CA137178); U.S. Department of Health and Human Services (HHSN268201600003C); Medical Research Council (14136); National Cancer Institute (R35CA197735); Division of Cancer Prevention, National Cancer Institute (P30CA014089); National Cancer Institute (P01 CA033619); Cancerfonden (14136); Johns Hopkins University (HHSN268201200008I); Medical Research Council (MR/M012190); National Heart, Lung, and Blood Institute (HHSN268201200008I); Cancer Research UK (C8221 / A29017); Bundesministerium für Bildung und Forschung (01ER0814); U.S. Department of Health and Human Services (R01 CA059045); U.S. Department of Health and Human Services (U01 CA164930); National Human Genome Research Institute (U01- HG004446); National Cancer Institute (U2C-CA252971); Cancer Council Victoria (14136); U.S. Department of Health and Human Services (R01 CA242218); Deutsche Forschungsgemeinschaft (KL 2354/3‐1); Institut Gustave-Roussy (14136); National Institutes of Health (5u01ca164930-04); Cancer Research UK (209057); National Cancer Institute (R01CA197350); Deutsche Forschungsgemeinschaft (CH 117/1-1); Victorian Cancer Agency (MCRF‐18005); National Heart, Lung, and Blood Institute (HHSN268201600001C); National Cancer Institute (U01CA122839); Cancer Council Victoria (209057); Institut Gustave-Roussy (1000143); World Cancer Research Fund (1000143); National Institutes of Health (5k05ca154337-05); Bundesministerium für Bildung und Forschung (MR/M012190/1); National Institutes of Health (HHSN268201600003C); Medical Research Council (UM1 CA186107); National Cancer Institute (R01 CA081488); National Institute of Diabetes and Digestive and Kidney Diseases (P30‐DK‐034987); Deutsche Forschungsgemeinschaft (RO 2270/8‐1); Associazione Italiana per la Ricerca sul Cancro (1000143); National Heart, Lung, and Blood Institute (CA186107); National Institute of Diabetes and Digestive and Kidney Diseases (P30DK-056350); Swedish Cancer Foundation (UM1 CA186107); Deutsches Krebsforschungszentrum (UM1 CA186107); Medical Research Council (1000143); National Cancer Institute (CA015704); National Cancer Institute (01KH0404); Institut National de la Santé et de la Recherche Médicale (MR/M012190/1); National Institutes of Health (7r01ca197350-06); U.S. Department of Health and Human Services (U19 CA148107); Ministerio de Economía y Competitividad (UM1 CA186107); National Cancer Institute (CA-186107); National Heart, Lung, and Blood Institute (HHSN268201200008C); Instituto de Salud Carlos III (PI14/00613); Centers for Disease Control and Prevention (NU58DP006333); National Institutes of Health (HHSN268201600004C); Medical Research Council (MR/M012190/1); National Cancer Institute (R01CA201407); Institut National de la Santé et de la Recherche Médicale (1000143); National Cancer Institute (R01-CA137178); Johns Hopkins University (P30CA006973); U.S. Department of Health and Human Services (P30-CA015704); National Cancer Institute (R01 CA066635); Cancer Research UK (A19167); Office of Research Infrastructure Programs, National Institutes of Health (S10OD028685); Swedish Cancer Foundation (209057); National Cancer Institute (U01 HG 004438); National Health and Medical Research Council (509348); Cancer Research UK (A29017); National Cancer Institute (R01CA242218); Associazione Italiana per la Ricerca sul Cancro (MR/M012190/1); Mutuelle Générale de l'Education Nationale (1000143); National Institute for Health and Care Research (UM1 CA167552); National Cancer Institute (U54CA233465); Associazione Italiana per la Ricerca sul Cancro (14136); National Institute for Health and Care Research (CA015704); Agència de Gestió d'Ajuts Universitaris i de Recerca (grant 2017SGR723); Ministerio de Economía y Competitividad (14136); Ministerio de Economía y Competitividad (MR/M012190/1); National Cancer Institute (CA059045); Division of Cancer Prevention, National Cancer Institute (U01 CA167552); National Institutes of Health (3um1ca186107-03s1); National Cancer Institute (209057); National Cancer Institute (U01 CA086308); Deutsche Krebshilfe (UM1 CA186107); Associazione Italiana per la Ricerca sul Cancro (209057); Bundesministerium für Bildung und Forschung (01ER0815); U.S. Department of Health and Human Services (K05 CA154337); Mutuelle Générale de l'Education Nationale (209057); National Cancer Institute (CA137088); Institut National de la Santé et de la Recherche Médicale (14136); National Health and Medical Research Council (209057, 251553 and 504711); Cancer Research UK (C588 / A19167); National Cancer Institute (U01CA261961); Damon Runyon Cancer Research Foundation (R01CA136726); National Cancer Institute (U01 CA167551); Cancer Research UK (14136); Cancer Research UK (1000143); Cancer Research UK (UM1 CA186107); National Institute for Health and Care Research (UM1 CA186107); National Cancer Institute (01ER1505B); American Cancer Society (R35 CA197735); National Heart, Lung, and Blood Institute (CA167552); Deutsche Krebshilfe (209057); National Cancer Institute (CA054281); National Heart, Lung, and Blood Institute (P30 CA015704); National Cancer Institute (U01 CA164930); National Institutes of Health (14136); Cancer Research UK (MR/M012190/1); Institut Gustave-Roussy (UM1 CA186107); National Cancer Institute (1000143); Swedish Cancer Foundation (MR/M012190/1); National Cancer Institute (R01 CA273198); Mutuelle Générale de l'Education Nationale (UM1 CA186107); National Institutes of Health (HHSN268201600001C); National Health and Medical Research Council (209057); National Cancer Institute (U10 CA037429); National Institute for Health and Care Research (1000143); Fundación Científica Asociación Española Contra el Cáncer (GCTRA18022MORE); World Cancer Research Fund (UM1 CA186107); National Institutes of Health (HHSN268201200008I); Division of Cancer Prevention, National Cancer Institute (CA167552); Deutsche Forschungsgemeinschaft (BR 1704/6–4); Conseil Régional des Pays de la Loire (PHRC-BRD09/C); U.S. Department of Health and Human Services (HHSN268201600004 C); Deutsches Krebsforschungszentrum (209057); Associazione Italiana per la Ricerca sul Cancro (UM1 CA186107); Xarxa de Bancs de Tumors de Catalunya (PT13/0010/0013); National Heart, Lung, and Blood Institute (UM1 CA186107); National Heart, Lung, and Blood Institute (HHSN268201600003C); National Institutes of Health (209057); National Health and Medical Research Council (P30 DK034987); Ligue Contre le Cancer (1000143); Ministerio de Economía y Competitividad (1000143); Deutsches Krebsforschungszentrum (14136); National Cancer Institute (U01 AG018033); National Institutes of Health (3r01ca201407-02s1); National Institutes of Health (HHSN268201600002C); Deutsche Krebshilfe (1000143); National Cancer Institute (CA81488); Cancer Research UK (C8221/A29017 to EPIC-Oxford); U.S. Department of Health and Human Services (R01 CA197350); Swedish Cancer Foundation (1000143); Bundesministerium für Bildung und Forschung (209057); Instituto de Salud Carlos III (2017SGR723); National Institutes of Health (1000143); National Cancer Institute (CA167551); Vetenskapsrådet (1000143); National Cancer Institute (CA063464); U.S. Department of Health and Human Services (R01 CA081488); Medical Research Council (209057); National Cancer Institute (14136); National Cancer Institute (P30DK034987); National Institutes of Health (5r01ca242218-05); Division of Cancer Prevention, National Cancer Institute (P30 CA006973); Deutsches Krebsforschungszentrum (MR/M012190/1); National Institutes of Health (5u01ca137088-08); National Institutes of Health (MR/M012190/1); National Cancer Institute (MR/M012190/1); National Health and Medical Research Council (504711); National Human Genome Research Institute (U01-HG004438); National Heart, Lung, and Blood Institute (HHSN268201600002C); Ministerio de Economía y Competitividad (209057); Institut Gustave-Roussy (209057); National Cancer Institute (R01 CA060987); National Institutes of Health (5r01ca081488-10); Bundesministerium für Bildung und Forschung (01KH0404); National Institute for Health and Care Research (MR/M012190/1); National Institutes of Health (3p30ca015704-49s4); National Cancer Institute (01ER0815); Vetenskapsrådet (MR/M012190/1); Deutsches Krebsforschungszentrum (1000143); National Institutes of Health (U01-CA167552); National Institutes of Health (U54CA233465); National Institutes of Health (U19 CA148107); National Institutes of Health (U01 CA137088); National Institutes of Health (R01 CA143237); National Institutes of Health (DK034987); National Institutes of Health (R37 CA054281); National Institutes of Health (P01CA055075); National Institutes of Health (R01CA137178); National Institutes of Health (R01 CA 151993); National Institutes of Health (UM1 CA167552); National Institutes of Health (UM1 CA182883); National Institute for Health and Care Research (14136); National Institutes of Health (P30-CA006973); National Institutes of Health (R01 CA059045); National Institutes of Health (R35 CA197735); National Institutes of Health (P30DK034987); National Institutes of Health (U01 CA122839); National Institutes of Health (CA006973); National Institutes of Health (U01 CA164930); National Institutes of Health (P30 CA015704); National Institutes of Health (R01CA176272); National Institutes of Health (R01 CA063464); National Institutes of Health (K05CA154337); National Institutes of Health (CA015704); National Institutes of Health (R01 CA206279); National Institutes of Health (UM1‐CA‐186107); National Institutes of Health (R01-CA201407); National Institutes of Health (P01 CA033619); National Institutes of Health (U01 CA167551); National Institutes of Health (R01 CA242218); National Institutes of Health (CA-167552); National Institutes of Health (P01-CA-087969); National Institutes of Health (U01 HG 004438); National Institutes of Health (P30‐CA014089); National Institutes of Health (CA186107); National Institutes of Health (R01 CA248857); National Institutes of Health (R01 CA060987); National Institutes of Health (U10 CA037429); National Institutes of Health (CA087969); National Institutes of Health (R01 CA197350); National Institutes of Health (CA197735); National Institutes of Health (CA055075); National Institutes of Health (CA143237); National Institutes of Health (R01 CA042182); National Institutes of Health (R0CA201407); National Institutes of Health (CA151993); National Institutes of Health (U01-HG004446); National Institutes of Health (R01 CA81488); National Institutes of Health (CA81488); National Institutes of Health (Z01 CP010200); National Institutes of Health (R01 CA081488); National Institutes of Health (R01 CA066635); Medical Research Council (MR/M012190/1 to EPIC-Oxford); National Institutes of Health (R01 CA048998); National Institutes of Health (CA242218); Vetenskapsrådet (209057); National Cancer Institute (R01-CA151993); National Cancer Institute (R01 CA042182); U.S. Department of Health and Human Services (HHSN268201600001 C); U.S. Department of Health and Human Services (U01 CA137088)

Based on 66 listed funder(s).

Publication

Published: 2023-12-19 · Cancer Epidemiol Biomarkers Prev · vol. 33 · issue 3 · pp. 400–410
Publisher: American Association for Cancer Research
Cited: 19 citations · more than 95% of similar papers · 4.4× the field average
Impact: Top 10% most cited in its field
References: 58 works
Access: Open access (repository copy)
Research areas: Nutritional Studies and Diet · Genetic Associations and Epidemiology · Meat and Animal Product Quality
Keywords: Red meat, Colorectal cancer, Processed meat, Confidence interval, Medicine, Genome-wide association study, Genotyping, Quartile, Single-nucleotide polymorphism, Internal medicine, Cancer, Genetics, Biology, Genotype, Food science, Gene, Pathology
MeSH: humans, colorectal neoplasms, risk factors, meat, gene-environment interaction, red meat

DOI ↗PubMed Central ↗OpenAlex ↗

72 authors

From US, ES, FR, GB, NL, FI, IL, SE, DE, CN, CA, AU

Mariana Carla Stern · correspondingUniversity of Southern California; USC Norris Comprehensive Cancer Center
Joel Sanchez MendezUniversity of Southern California; USC Norris Comprehensive Cancer Center
Andre E. KimUniversity of Southern California; USC Norris Comprehensive Cancer Center
Mireia Obón‐SantacanaBellvitge University Hospital; Institut d'Investigació Biomédica de Bellvitge; Institut Català d'Oncologia; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública
Ferrán Moratalla-NavarroBellvitge University Hospital; Institut d'Investigació Biomédica de Bellvitge; Institut Català d'Oncologia; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública; Universitat de Barcelona
Vicente MartínCentro de Investigación Biomédica en Red de Epidemiología y Salud Pública; Universidad de León

Abstract

Background

High red meat and/or processed meat consumption are established colorectal cancer risk factors. We conducted a genome-wide gene-environment (GxE) interaction analysis to identify genetic variants that may modify these associations.

Methods

A pooled sample of 29,842 colorectal cancer cases and 39,635 controls of European ancestry from 27 studies were included. Quantiles for red meat and processed meat intake were constructed from harmonized questionnaire data. Genotyping arrays were imputed to the Haplotype Reference Consortium. Two-step EDGE and joint tests of GxE interaction were utilized in our genome-wide scan.

Results

Meta-analyses confirmed positive associations between increased consumption of red meat and processed meat with colorectal cancer risk [per quartile red meat OR = 1.30; 95% confidence interval (CI) = 1.21-1.41; processed meat OR = 1.40; 95% CI = 1.20-1.63]. Two significant genome-wide GxE interactions for red meat consumption were found. Joint GxE tests revealed the rs4871179 SNP in chromosome 8 (downstream of HAS2); greater than median of consumption ORs = 1.38 (95% CI = 1.29-1.46), 1.20 (95% CI = 1.12-1.27), and 1.07 (95% CI = 0.95-1.19) for CC, CG, and GG, respectively. The two-step EDGE method identified the rs35352860 SNP in chromosome 18 (SMAD7 intron); greater than median of consumption ORs = 1.18 (95% CI = 1.11-1.24), 1.35 (95% CI = 1.26-1.44), and 1.46 (95% CI = 1.26-1.69) for CC, CT, and TT, respectively.

Conclusions

We propose two novel biomarkers that support the role of meat consumption with an increased risk of colorectal cancer.

Impact

The reported GxE interactions may explain the increased risk of colorectal cancer in certain population subgroups.

Abstract via Europe PMC. Copyright remains with the authors or publisher.

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