title: Genome-wide association study identifies a new breast cancer susceptibility locus at 6q25.1.
abstract: We carried out a genome-wide association study among Chinese women to identify risk variants for breast cancer. After analyzing 607,728 SNPs in 1,505 cases and 1,522 controls, we selected 29 SNPs for a fast-track replication in an independent set of 1,554 cases and 1,576 controls. We further investigated four replicated loci in a third set of samples comprising 3,472 cases and 900 controls. SNP rs2046210 at 6q25.1, located upstream of the gene encoding estrogen receptor alpha (ESR1), showed strong and consistent association with breast cancer across all three stages. Adjusted odds ratio (95% CI) were 1.36 (1.24-1.49) and 1.59 (1.40-1.82), respectively, for genotypes A/G and A/A versus G/G (P for trend 2.0 x 10(-15)) in the pooled analysis of samples from all three stages. We also found a similar, albeit weaker, association in an independent study comprising 1,591 cases and 1,466 controls of European ancestry (P(trend) = 0.01). These results strongly implicate 6q25.1 as a susceptibility locus for breast cancer.
authors.affiliation: Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. wei.zheng@vanderbilt.edu
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: Jirong
authors.initials: J
authors.lastname: Long
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Gao
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
authors.forename: Yong-Bin
authors.initials: YB
authors.lastname: Xiang
authors.forename: Wanqing
authors.initials: W
authors.lastname: Wen
authors.forename: Shawn
authors.initials: S
authors.lastname: Levy
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Deming
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Haines
authors.forename: Kai
authors.initials: K
authors.lastname: Gu
authors.forename: Alecia Malin
authors.initials: AM
authors.lastname: Fair
authors.forename: Qiuyin
authors.initials: Q
authors.lastname: Cai
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Xiao-Ou
authors.initials: XO
authors.lastname: Shu
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D002896:Chromosomes, Human, Pair 6; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012307:Risk Factors
chemical_list: D047628:Estrogen Receptor alpha