Genome-wide association study identifies a new breast cancer susceptibility locus at 6q25.1.
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.
Zheng
Wei
W
Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. wei.zheng@vanderbilt.edu
Long
Jirong
J
Gao
Yu-Tang
YT
Li
Chun
C
Zheng
Ying
Y
Xiang
Yong-Bin
YB
Wen
Wanqing
W
Levy
Shawn
S
Deming
Sandra L
SL
Haines
Jonathan L
JL
Gu
Kai
K
Fair
Alecia Malin
AM
Cai
Qiuyin
Q
Lu
Wei
W
Shu
Xiao-Ou
XO
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
D047628:Estrogen Receptor alpha