title: Genome-wide association study in east Asians identifies novel susceptibility loci for breast cancer.
abstract: 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.
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
authors.forename: Jirong
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authors.lastname: Long
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authors.forename: Zefang
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authors.forename: Ui Soon
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authors.forename: Yong-Bing
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authors.lastname: Xiang
authors.forename: Kai
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authors.forename: Nathaniel
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authors.lastname: Rothman
authors.forename: Wenjing
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authors.forename: Yao
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authors.lastname: Liu
authors.forename: Keun-Young
authors.initials: KY
authors.lastname: Yoo
authors.forename: Dong-Young
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authors.lastname: Noh
authors.forename: Bok-Ghee
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authors.lastname: Han
authors.forename: Min Hyuk
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authors.lastname: Lee
authors.forename: Hong
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authors.lastname: Zheng
authors.forename: Lina
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authors.lastname: Zhang
authors.forename: Pei-Ei
authors.initials: PE
authors.lastname: Wu
authors.forename: Ya-Lan
authors.initials: YL
authors.lastname: Shieh
authors.forename: Sum Yin
authors.initials: SY
authors.lastname: Chan
authors.forename: Shenming
authors.initials: S
authors.lastname: Wang
authors.forename: Xiaoming
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authors.lastname: Xie
authors.forename: Sung-Won
authors.initials: SW
authors.lastname: Kim
authors.forename: Brian E
authors.initials: BE
authors.lastname: Henderson
authors.forename: Loic
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authors.lastname: Le Marchand
authors.forename: Hidemi
authors.initials: H
authors.lastname: Ito
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kasuga
authors.forename: Sei-Hyun
authors.initials: SH
authors.lastname: Ahn
authors.forename: Han Sung
authors.initials: HS
authors.lastname: Kang
authors.forename: Kelvin Y K
authors.initials: KY
authors.lastname: Chan
authors.forename: Hiroji
authors.initials: H
authors.lastname: Iwata
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Tsugane
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.forename: Xiao-Ou
authors.initials: XO
authors.lastname: Shu
authors.forename: Dae-Hee
authors.initials: DH
authors.lastname: Kang
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D044466:Asian People; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000235:genetics; D005202:Asia, Eastern / Q000453:epidemiology; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008875:Middle Aged
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; C410585:TAB2 protein, human