Gene-environment interaction involving recently identified colorectal cancer susceptibility loci

Elizabeth D. Kantor, Carolyn M. Hutter, Jessica Minnier, Sonja I. Berndt, Hermann Brenner, Bette J. Caan, Peter T. Campbell, Christopher S. Carlson, Graham Casey, Andrew T. Chan, Jenny Chang-Claude, Stephen J. Chanock, Michelle Cotterchio, Mengmeng Du, David Duggan, Charles S. Fuchs, Edward L. Giovannucci, Jian Gong, Tabitha A. Harrison, Richard B. HayesBrian E. Henderson, Michael Hoffmeister, John L. Hopper, Mark A. Jenkins, Shuo Jiao, Laurence N. Kolonel, Loic Le Marchand, Mathieu Lemire, Jing Ma, Polly A. Newcomb, Heather M. Ochs-Balcom, Bethann M. Pflugeisen, John D. Potter, Anja Rudolph, Robert E. Schoen, Daniela Seminara, Martha L. Slattery, Deanna L. Stelling, Fridtjof Thomas, Mark Thornquist, Cornelia M. Ulrich, Greg S. Warnick, Brent W. Zanke, Ulrike Peters, Li Hsu, Emily White

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Background: Genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) that are associated with risk of colorectal cancer. Prior research has evaluated the presence of gene- environment interaction involving the first 10 identified susceptibility loci, but little work has been conducted on interaction involving SNPs at recently identified susceptibility loci, including: rs10911251, rs6691170, rs6687758, rs11903757, rs10936599, rs647161, rs1321311, rs719725, rs1665650, rs3824999, rs7136702, rs11169552, rs59336, rs3217810, rs4925386, and rs2423279.

Methods: Data on 9, 160 cases and 9, 280 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and Colon Cancer Family Registry (CCFR) were used to evaluate the presence of interaction involving the above-listed SNPs and sex, body mass index (BMI), alcohol consumption, smoking, aspirin use, postmenopausal hormone (PMH) use, as well as intake of dietary calcium, dietary fiber, dietary folate, red meat, processed meat, fruit, and vegetables. Interaction was evaluated using a fixed effects metaanalysis of an efficient Empirical Bayes estimator, and permutation was used to account for multiple comparisons.

Results: None of the permutation-adjusted P values reached statistical significance.

Conclusions: The associations between recently identified genetic susceptibility loci and colorectal cancer are not strongly modified by sex, BMI, alcohol, smoking, aspirin, PMH use, and various dietary factors.

Impact: Results suggest no evidence of strong gene-environment interactions involving the recently identified 16 susceptibility loci for colorectal cancer taken one at a time.

Original languageEnglish (US)
Pages (from-to)1824-1833
Number of pages10
JournalCancer Epidemiology Biomarkers and Prevention
Volume23
Issue number9
DOIs
StatePublished - Sep 1 2014

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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