title: Genome-Wide Interaction Analyses between Genetic Variants and Alcohol Consumption and Smoking for Risk of Colorectal Cancer.
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.
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
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authors.lastname: Gong
authors.affiliation: Division of Genomic Medicine, National Human Genome Research Institute, Bethesda, Maryland, United States of America.
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Hutter
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Polly A
authors.initials: PA
authors.lastname: Newcomb
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.|Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, United States of America.
authors.forename: Cornelia M
authors.identifier: http://orcid.org/0000-0001-7641-059X
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authors.lastname: Ulrich
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Stephanie A
authors.identifier: http://orcid.org/0000-0002-8713-4583
authors.initials: SA
authors.lastname: Bien
authors.affiliation: Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, United States of America.
authors.forename: Peter T
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authors.lastname: Campbell
authors.affiliation: Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: John A
authors.initials: JA
authors.lastname: Baron
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: Sonja I
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authors.lastname: Berndt
authors.affiliation: CHU Nantes, Service de Génétique Médicale, Nantes, France.
authors.forename: Stephane
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authors.lastname: Bezieau
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.|German Cancer Consortium (DKTK), Heidelberg, Germany.
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authors.affiliation: Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Graham
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authors.affiliation: 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.
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authors.initials: AT
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authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Jenny
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authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
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authors.affiliation: Translational Genomics Research Institute, Phoenix, Arizona, United States of America.
authors.forename: David
authors.identifier: http://orcid.org/0000-0002-4696-3940
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authors.affiliation: Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Jane C
authors.initials: JC
authors.lastname: Figueiredo
authors.affiliation: Department of Surgery, University Health Network Toronto General Hospital, Toronto, Ontario, Canada.
authors.forename: Steven
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authors.lastname: Gallinger
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital, Boston Massachusetts, United States of America.
authors.forename: Edward L
authors.initials: EL
authors.lastname: Giovannucci
authors.affiliation: Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Haile
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Tabitha A
authors.initials: TA
authors.lastname: Harrison
authors.affiliation: Division of Epidemiology, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Hayes
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Michael
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authors.lastname: Hoffmeister
authors.affiliation: Melbourne School of Population Health, The University of Melbourne, Melbourne, Australia.
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authors.forename: Thomas J
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authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Jihyoun
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authors.affiliation: Melbourne School of Population Health, The University of Melbourne, Melbourne, Australia.
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authors.initials: MA
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authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Jonathan
authors.identifier: http://orcid.org/0000-0001-8084-1608
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authors.affiliation: CHU Nantes, Service de Génétique Médicale, Nantes, France.
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authors.affiliation: Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, United States of America.
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authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
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authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Scottsdale, Arizona, United States of America.
authors.forename: Noralane M
authors.initials: NM
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authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.|Centre for Public Health Research, Massey University, Wellington, New Zealand.
authors.forename: John D
authors.initials: JD
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authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
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authors.affiliation: Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Schoen
authors.affiliation: Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany.
authors.forename: Petra
authors.identifier: http://orcid.org/0000-0002-2397-9480
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authors.lastname: Schrotz-King
authors.affiliation: Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Maryland, United States of America.
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authors.affiliation: Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah, United States of America.
authors.forename: Martha L
authors.initials: ML
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authors.affiliation: Departments of Laboratory Medicine and Pathology and Laboratory Genetics, Mayo Clinic, Rochester, Minnesota, United States of America.
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authors.initials: SN
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authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
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authors.forename: Reka
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authors.affiliation: Department of Epidemiology, The University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Robert
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authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Emily
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authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Shuo
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authors.affiliation: Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
authors.forename: Mathieu
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authors.lastname: Lemire
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Li
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mesh_terms: D000368:Aged; D000428:Alcohol Drinking / Q000235:genetics* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000235:genetics* / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C000618218:MFSD14B protein, human; D026901:Membrane Transport Proteins; D025521:Tumor Suppressor Proteins