A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry

Abstract Background Genome-wide studies of gene–environment interactions (G×E) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide G×E analysis of ~ 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer. Methods Analyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene–environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs. Results Assuming a 1 × 10–5 prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability研究背景 全基因组基因-环境交互作用（gene–environment interactions, G×E）研究可结合生活方式/环境暴露因素，鉴定与疾病风险相关的遗传变异。本研究针对总体乳腺癌风险以及雌激素受体阳性（estrogen receptor positive, ER+）乳腺癌风险，开展了一项涵盖约760万个常见遗传变异与7种生活方式/环境危险因素的全基因组G×E分析。 研究方法 本研究依托乳腺癌协会联盟（Breast Cancer Association Consortium）的欧洲血统人群数据开展分析，共纳入72285例乳腺癌患者与80354例对照个体。针对总体乳腺癌及ER+乳腺癌风险，采用标准非条件logistic回归模型与似然比检验评估基因-环境交互作用；并采用贝叶斯错误发现概率（Bayesian False Discovery Probability）评估每一对单核苷酸多态性（single nucleotide polymorphism, SNP）-危险因素组合的显著性。 研究结果 本研究假设每一对SNP-危险因素组合的真实关联先验概率为1×10^–5，并采用贝叶斯错误发现概率