Genome-Wide Association Study in East Asians Identifies Novel Susceptibility Loci for Breast Cancer

• DOI: 10.1371/journal.pgen.1002532
• Publication Date: 2012-02-23T21:56:50Z
• Authors: Jirong Long; Qiuyin Cai; Hyuna Sung; Jiajun Shi; Ben Zhang; Ji-Yeob Choi; Wanqing Wen; Ryan J. Delahanty; Wei Lu; Yu-Tang Gao; Hongbing Shen; Sue K. Park; Kexin Chen; Chen-Yang Shen; Zefang Ren; Christopher A. Ha...; Keitaro Matsuo; Mi Kyung Kim; Ui Soon Khoo; Motoki Iwasaki; Ying Zheng; Yong-Bing Xiang; Kai Gu; Nathaniel Rothman; Wenjing Wang; Zhibin Hu; Yao Liu; Keun-Young Yoo; Dong-Young Noh; Bok-Ghee Han; Min Hyuk Lee; Hong Zheng; Lina Zhang; Pei-Ei Wu; Ya-Lan Shieh; Sum Yin Chan; Shenming Wang; Xiaoming Xie; Sung-Won Kim; Brian E. Henderson; Loic Le Marchand; Hidemi Ito; Yoshio Kasuga; Sei-Hyun Ahn; Han Sung Kang; Kelvin Y. K. Chan; Hiroji Iwata; Shoichiro Tsugane; Chun Li; Xiao-Ou Shu; Dae-Hee Kang; Wei Zheng
• Keywords: Genome-wide Association Study; SNP; Genetic Association

Genetic factors play an important role in the etiology of both sporadic and familial breast cancer. We aimed to discover novel genetic susceptibility loci for conducted a four-stage genome-wide association study (GWAS) 19,091 cases 20,606 controls East-Asian descent including Chinese, Korean, Japanese women. After analyzing 690,947 SNPs 2,918 2,324 controls, we evaluated 5,365 replication 3,972 3,852 controls. Ninety-four were further 5,203 5,138 finally top 22 investigated up 17,423 additional subjects (7,489 9,934 controls). SNP rs9485372, near TGF-β activated kinase (TAB2) gene chromosome 6q25.1, showed consistent with cancer risk across all four stages, P-value 3.8×10−12 combined analysis samples. Adjusted odds ratios (95% confidence intervals) 0.89 (0.85–0.94) 0.80 (0.75–0.86) A/G A/A genotypes, respectively, compared genotype G/G. rs9383951 (P = 1.9×10−6 from samples), located intron 5 ESR1 gene, rs7107217 4.6×10−7), at 11q24.3, also each stages. This provides strong evidence locus represented by TAB2 (6q25.1), identifies two possible respectively.