Genome-wide association study in east Asians identifies novel susceptibility loci for breast cancer.

Genome-wide association study in east Asians identifies novel susceptibility loci for breast cancer.

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 breast cancer. We conducted a four-stage genome-wide association study (GWAS) in 19,091 cases and 20,606 controls of East-Asian descent inclu...

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Autores principales: 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 Haiman, 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
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2012
Materias:
Genetics
QH426-470
Acceso en línea:https://doaj.org/article/f75dd7743701428380d28e90b5183179
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Sumario: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 breast cancer. We conducted a four-stage genome-wide association study (GWAS) in 19,091 cases and 20,606 controls of East-Asian descent including Chinese, Korean, and Japanese women. After analyzing 690,947 SNPs in 2,918 cases and 2,324 controls, we evaluated 5,365 SNPs for replication in 3,972 cases and 3,852 controls. Ninety-four SNPs were further evaluated in 5,203 cases and 5,138 controls, and finally the top 22 SNPs were investigated in up to 17,423 additional subjects (7,489 cases and 9,934 controls). SNP rs9485372, near the TGF-β activated kinase (TAB2) gene in chromosome 6q25.1, showed a consistent association with breast cancer risk across all four stages, with a P-value of 3.8×10(-12) in the combined analysis of all samples. Adjusted odds ratios (95% confidence intervals) were 0.89 (0.85-0.94) and 0.80 (0.75-0.86) for the A/G and A/A genotypes, respectively, compared with the genotype G/G. SNP rs9383951 (P = 1.9×10(-6) from the combined analysis of all samples), located in intron 5 of the ESR1 gene, and SNP rs7107217 (P = 4.6×10(-7)), located at 11q24.3, also showed a consistent association in each of the four stages. This study provides strong evidence for a novel breast cancer susceptibility locus represented by rs9485372, near the TAB2 gene (6q25.1), and identifies two possible susceptibility loci located in the ESR1 gene and 11q24.3, respectively.

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