Kantor Elizabeth D, Hutter Carolyn M, Minnier Jessica, Berndt Sonja I, Brenner Hermann, Caan Bette J, Campbell Peter T, Carlson Christopher S, Casey Graham, Chan Andrew T, Chang-Claude Jenny, Chanock Stephen J, Cotterchio Michelle, Du Mengmeng, Duggan David, Fuchs Charles S, Giovannucci Edward L, Gong Jian, Harrison Tabitha A, Hayes Richard B, Henderson Brian E, Hoffmeister Michael, Hopper John L, Jenkins Mark A, Jiao Shuo, Kolonel Laurence N, Le Marchand Loic, Lemire Mathieu, Ma Jing, Newcomb Polly A, Ochs-Balcom Heather M, Pflugeisen Bethann M, Potter John D, Rudolph Anja, Schoen Robert E, Seminara Daniela, Slattery Martha L, Stelling Deanna L, Thomas Fridtjof, Thornquist Mark, Ulrich Cornelia M, Warnick Greg S, Zanke Brent W, Peters Ulrike, Hsu Li, White Emily
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington.
Division of Cancer Control and Population Sciences, National Cancer Institute, NIH, Bethesda, Maryland.
Cancer Epidemiol Biomarkers Prev. 2014 Sep;23(9):1824-33. doi: 10.1158/1055-9965.EPI-14-0062. Epub 2014 Jul 3.
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.
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 meta-analysis of an efficient Empirical Bayes estimator, and permutation was used to account for multiple comparisons.
None of the permutation-adjusted P values reached statistical significance.
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.
Results suggest no evidence of strong gene-environment interactions involving the recently identified 16 susceptibility loci for colorectal cancer taken one at a time.
全基因组关联研究已鉴定出多个与结直肠癌风险相关的单核苷酸多态性（SNP）。既往研究评估了涉及最初鉴定出的10个易感位点的基因-环境相互作用，但针对最近鉴定出的易感位点（包括：rs10911251、rs6691170、rs6687758、rs11903757、rs10936599、rs647161、rs1321311、rs719725、rs1665650、rs3824999、rs7136702、rs11169552、rs59336、rs3217810、rs4925386和rs2423279）的SNP之间相互作用的研究较少。
来自结直肠癌遗传学与流行病学联盟（GECCO）和结肠癌家族登记处（CCFR）的9160例病例和9280例对照的数据，用于评估上述SNP与性别、体重指数（BMI）、饮酒、吸烟、阿司匹林使用、绝经后激素（PMH）使用以及膳食钙、膳食纤维、膳食叶酸、红肉、加工肉、水果和蔬菜摄入量之间的相互作用。使用有效经验贝叶斯估计量的固定效应荟萃分析评估相互作用，并采用置换法处理多重比较。
经置换调整的P值均未达到统计学显著性。
最近鉴定出的遗传易感位点与结直肠癌之间的关联，未受到性别、BMI、酒精、吸烟、阿司匹林、PMH使用及各种饮食因素的强烈影响。
结果表明，一次考虑一个最近鉴定出的16个结直肠癌易感位点时，没有证据显示存在强烈的基因-环境相互作用。
