title: Evaluation of functional genetic variants for breast cancer risk: results from the Shanghai breast cancer study.
abstract: In previous studies among 1,144 cases and 1,256 controls recruited in stage 1 of the Shanghai Breast Cancer Study (SBCS I; 1996-1998), 18 known or potentially functional single nucleotide polymorphisms (SNPs) in 16 genes were found to be associated with breast cancer risk. The authors evaluated these associations among 1,918 cases and 1,819 controls recruited in stage 2 of the SBCS (SBCS II; 2002-2005) using genetic effect models and subgroup analyses predetermined from SBCS I results. Five SNPs (AHR rs2066853, ATM rs1003623, ESR1 rs2234693, GSTP1 rs1695, and SHBG rs6259) showed generally consistent results in SBCS I and SBCS II and statistically significant associations with breast cancer risk in combined analyses, mostly in subgroups defined by age or menopausal status. Further, the relation between breast cancer risk and SHBG rs6259 was found to vary by body mass index (weight (kg)/height (m)(2)) (P for interaction = 0.003). The strongest reduction in risk associated with SHBG rs6259 was found for lean (body mass index <23) postmenopausal minor allele carriers (odds ratio = 0.6, 95% confidence interval: 0.5, 0.8; P = 4.6 × 10(-4)). This biologically plausible and highly significant finding provides strong evidence for a true association among Asian women. This study also highlights the value of gene-environment interaction analyses in evaluating genetic factors for complex diseases.
authors: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors: Ben
authors: B
authors: Zhang
authors: Alicia
authors: A
authors: Beeghly-Fadiel
authors: Wei
authors: W
authors: Lu
authors: Qiuyin
authors: Q
authors: Cai
authors: Yong-Bing
authors: YB
authors: Xiang
authors: Ying
authors: Y
authors: Zheng
authors: Jirong
authors: J
authors: Long
authors: Chuanzhong
authors: C
authors: Ye
authors: Kai
authors: K
authors: Gu
authors: Xiao-Ou
authors: XO
authors: Shu
authors: Yutang
authors: Y
authors: Gao
authors: Wei
authors: W
authors: Zheng
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics; D012307:Risk Factors; D055815:Young Adult
chemical_list: D011956:Receptors, Cell Surface; C063572:sex hormone-binding globulin receptor