Journal article
Genome-Wide Interaction Analyses between Genetic Variants and Alcohol Consumption and Smoking for Risk of Colorectal Cancer
PLoS genetics, Vol.12(10), pp.e1006296-e1006296
10/2016
DOI: 10.1371/journal.pgen.1006296
PMCID: PMC5065124
PMID: 27723779
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.
Details
- Title: Subtitle
- Genome-Wide Interaction Analyses between Genetic Variants and Alcohol Consumption and Smoking for Risk of Colorectal Cancer
- Creators
- Jian Gong - Fred Hutch Cancer CenterCarolyn M Hutter - National Human Genome Research InstitutePolly A Newcomb - Fred Hutch Cancer CenterCornelia M Ulrich - University of UtahStephanie A Bien - Fred Hutch Cancer CenterPeter T Campbell - Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, United States of AmericaJohn A Baron - Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of AmericaSonja I Berndt - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of AmericaStephane Bezieau - CHU Nantes, Service de Génétique Médicale, Nantes, FranceHermann Brenner - German Cancer Research CenterGraham Casey - Keck School of Medicine, University of Southern California, Los Angeles, California, United States of AmericaAndrew T ChanJenny Chang-Claude - German Cancer Research CenterMengmeng Du - Fred Hutch Cancer CenterDavid Duggan - Translational Genomics Research InstituteJane C Figueiredo - Keck School of Medicine, University of Southern California, Los Angeles, California, United States of AmericaSteven Gallinger - Department of Surgery, University Health Network Toronto General Hospital, Toronto, Ontario, CanadaEdward L Giovannucci - Brigham and Women's HospitalRobert W Haile - Keck School of Medicine, University of Southern California, Los Angeles, California, United States of AmericaTabitha A Harrison - Fred Hutch Cancer CenterRichard B Hayes - Division of Epidemiology, New York University School of Medicine, New York, New York, United States of AmericaMichael Hoffmeister - German Cancer Research CenterJohn L Hopper - The University of MelbourneThomas J Hudson - Ontario Institute for Cancer ResearchJihyoun Jeon - Fred Hutch Cancer CenterMark A Jenkins - The University of MelbourneJonathan Kocarnik - Fred Hutch Cancer CenterSébastien Küry - CHU Nantes, Service de Génétique Médicale, Nantes, FranceLoic Le Marchand - University of Hawaii SystemYi Lin - Fred Hutch Cancer CenterNoralane M Lindor - Department of Health Sciences Research, Mayo Clinic, Scottsdale, Arizona, United States of AmericaReiko Nishihara - Dana-Farber Cancer Institute, Harvard School of Public Health, Boston, Massachusetts, United States of AmericaShuji Ogino - Harvard Medical SchoolJohn D Potter - Massey UniversityAnja Rudolph - German Cancer Research CenterRobert E Schoen - University of Pittsburgh Medical CenterPetra Schrotz-King - National Center for Tumor DiseasesDaniela Seminara - Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Maryland, United States of AmericaMartha L Slattery - University of UtahStephen N Thibodeau - Departments of Laboratory Medicine and Pathology and Laboratory Genetics, Mayo Clinic, Rochester, Minnesota, United States of AmericaMark Thornquist - Fred Hutch Cancer CenterReka Toth - National Center for Tumor DiseasesRobert Wallace - University of IowaEmily White - Fred Hutch Cancer CenterShuo Jiao - Fred Hutch Cancer CenterMathieu Lemire - Ontario Institute for Cancer ResearchLi Hsu - Fred Hutch Cancer CenterUlrike Peters - Fred Hutch Cancer CenterCCFR and GECCO
- Resource Type
- Journal article
- Publication Details
- PLoS genetics, Vol.12(10), pp.e1006296-e1006296
- DOI
- 10.1371/journal.pgen.1006296
- PMID
- 27723779
- PMCID
- PMC5065124
- NLM abbreviation
- PLoS Genet
- ISSN
- 1553-7390
- eISSN
- 1553-7404
- Grant note
- HHSN268201100004I / NHLBI NIH HHS HHSN268201100004C / WHI NIH HHS P30 CA071789 / NCI NIH HHS UM1 CA167551 / NCI NIH HHS HHSN268201100002C / WHI NIH HHS K05 CA152715 / NCI NIH HHS R01 CA195789 / NCI NIH HHS HHSN268201100003C / WHI NIH HHS R01 CA143237 / NCI NIH HHS R01 CA120582 / NCI NIH HHS R01 CA063464 / NCI NIH HHS U24 CA097735 / NCI NIH HHS U01 HG004446 / NHGRI NIH HHS P01 CA087969 / NCI NIH HHS U24 CA074783 / NCI NIH HHS R01 CA076366 / NCI NIH HHS R35 CA197735 / NCI NIH HHS HHSN268201100046C / NHLBI NIH HHS R37 CA054281 / NCI NIH HHS P01 CA033619 / NCI NIH HHS U01 CA164930 / NCI NIH HHS U24 CA074794 / NCI NIH HHS HHSN271201100004C / NIA NIH HHS K07 CA190673 / NCI NIH HHS U01 CA097735 / NCI NIH HHS R01 CA059045 / NCI NIH HHS U01 CA074783 / NCI NIH HHS U01 CA122839 / NCI NIH HHS P30 CA015083 / NCI NIH HHS HHSN268201100003I / NHLBI NIH HHS P01 CA055075 / NCI NIH HHS U01 CA206110 / NCI NIH HHS R01 CA137178 / NCI NIH HHS Z01 CP010200 / Intramural NIH HHS R01 CA048998 / NCI NIH HHS UM1 CA167552 / NCI NIH HHS HHSN268201100002I / NHLBI NIH HHS HHSN268201100001C / WHI NIH HHS R01 CA042182 / NCI NIH HHS U01 CA137088 / NCI NIH HHS P50 CA127003 / NCI NIH HHS U01 HG004438 / NHGRI NIH HHS P30 CA008748 / NCI NIH HHS U01 CA074794 / NCI NIH HHS UM1 CA186107 / NCI NIH HHS HHSN268201100001I / NHLBI NIH HHS K05 CA154337 / NCI NIH HHS R01 CA151993 / NCI NIH HHS R01 CA060987 / NCI NIH HHS
- Language
- English
- Date published
- 10/2016
- Academic Unit
- Epidemiology; Injury Prevention Research Center; Internal Medicine
- Record Identifier
- 9984364430202771
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