Genome-Wide Gene-Environment Interaction Analyses to Understand the Relationship between Red Meat and Processed Meat Intake and Colorectal Cancer Risk.
- Department of Population and Public Health Sciences and USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California.
- Unit of Biomarkers and Susceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L'Hospitalet del Llobregat, Barcelona, Spain.
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain.
- Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington.
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
- Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, North Carolina.
- Department of Population Science, American Cancer Society, Atlanta, Georgia.
- Department of Genetics, Stanford University, Stanford, California.
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
- Service de Génétique Médicale, Centre Hospitalier Universitaire (CHU) Nantes, Nantes, France.
- Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, the Netherlands.
- Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland.
- Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel.
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
- University of Hawaii Cancer Center, Honolulu, Hawaii.
- Prevention and Cancer Control, Cancer Care Ontario, Toronto, Ontario, Canada.
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
- Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, United Kingdom.
- Flinders Health and Medical Research Institute, Adelaide Institute for Sleep Health, Flinders University, Adelaide, South Australia, Australia.
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
- Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, Victoria, Australia.
- Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
- Department of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas.
- Department of Family Medicine, University of Virginia, Charlottesville, Virginia.
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York.
- Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.
- Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center, Duarte California.
- Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan.
- Departments of Epidemiology and Nutrition, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.
- Clinical and Translational Epidemiology Unit and Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
- Slone Epidemiology Center at, Boston University, Boston, Massachusetts.
- Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
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.
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