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Genome-Wide Interaction Analyses between Genetic Variants and Alcohol Consumption and Smoking for Risk of Colorectal Cancer.

About this Publication
Title
Genome-Wide Interaction Analyses between Genetic Variants and Alcohol Consumption and Smoking for Risk of Colorectal Cancer.
Pubmed ID
27723779 (View this publication on the PubMed website)
Digital Object Identifier
Publication
PLoS Genet. 2016 Oct; Volume 12 (Issue 10): Pages e1006296
Authors
Gong J, Hutter CM, Newcomb PA, Ulrich CM, Bien SA, Campbell PT, Baron JA, Berndt SI, Bezieau S, Brenner H, Casey G, Chan AT, Chang-Claude J, Du M, Duggan D, Figueiredo JC, Gallinger S, Giovannucci EL, Haile RW, Harrison TA, ...show more Hayes RB, Hoffmeister M, Hopper JL, Hudson TJ, Jeon J, Jenkins MA, Kocarnik J, Küry S, Le Marchand L, Lin Y, Lindor NM, Nishihara R, Ogino S, Potter JD, Rudolph A, Schoen RE, Schrotz-King P, Seminara D, Slattery ML, Thibodeau SN, Thornquist M, Toth R, Wallace R, White E, Jiao S, Lemire M, Hsu L, Peters U, CCFR and GECCO
Affiliations
  • Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
  • Division of Genomic Medicine, National Human Genome Research Institute, Bethesda, Maryland, United States of America.
  • Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, United States of America.
  • Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America.
  • CHU Nantes, Service de Génétique Médicale, Nantes, France.
  • Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
  • Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
  • Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
...show more
  • Translational Genomics Research Institute, Phoenix, Arizona, United States of America.
  • Department of Surgery, University Health Network Toronto General Hospital, Toronto, Ontario, Canada.
  • Channing Division of Network Medicine, Brigham and Women's Hospital, Boston Massachusetts, United States of America.
  • Division of Epidemiology, New York University School of Medicine, New York, New York, United States of America.
  • Melbourne School of Population Health, The University of Melbourne, Melbourne, Australia.
  • Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
  • Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, United States of America.
  • Department of Health Sciences Research, Mayo Clinic, Scottsdale, Arizona, United States of America.
  • Dana-Farber Cancer Institute, Harvard School of Public Health, Boston, Massachusetts, United States of America.
  • Harvard Medical School, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America.
  • Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States of America.
  • Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany.
  • Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Maryland, United States of America.
  • Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah, United States of America.
  • Departments of Laboratory Medicine and Pathology and Laboratory Genetics, Mayo Clinic, Rochester, Minnesota, United States of America.
  • Department of Epidemiology, The University of Iowa, Iowa City, Iowa, United States of America.
Abstract

Genome-wide association studies (GWAS) have identified many genetic susceptibility loci for colorectal cancer (CRC). However, variants in these loci explain only a small proportion of familial aggregation, and there are likely additional variants that are associated with CRC susceptibility. Genome-wide studies of gene-environment interactions may identify variants that are not detected in GWAS of marginal gene effects. To study this, we conducted a genome-wide analysis for interaction between genetic variants and alcohol consumption and cigarette smoking using data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Interactions were tested using logistic regression. We identified interaction between CRC risk and alcohol consumption and variants in the 9q22.32/HIATL1 (Pinteraction = 1.76×10-8; permuted p-value 3.51x10-8) region. Compared to non-/occasional drinking light to moderate alcohol consumption was associated with a lower risk of colorectal cancer among individuals with rs9409565 CT genotype (OR, 0.82 [95% CI, 0.74-0.91]; P = 2.1×10-4) and TT genotypes (OR,0.62 [95% CI, 0.51-0.75]; P = 1.3×10-6) but not associated among those with the CC genotype (p = 0.059). No genome-wide statistically significant interactions were observed for smoking. If replicated our suggestive finding of a genome-wide significant interaction between genetic variants and alcohol consumption might contribute to understanding colorectal cancer etiology and identifying subpopulations with differential susceptibility to the effect of alcohol on CRC risk.

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