Genome-wide association study identifies breast cancer risk variant at 10q21.2: results from the Asia Breast Cancer Consortium.

Abstract

Although approximately 20 common genetic susceptibility loci have been identified for breast cancer risk through genome-wide association studies (GWASs), genetic risk variants reported to date explain only a small fraction of heritability for this common cancer. We conducted a four-stage GWAS including 17 153 cases and 16 943 controls among East-Asian women to search for new genetic risk factors for breast cancer. After analyzing 684 457 SNPs in 2062 cases and 2066 controls (Stage I), we selected for replication among 5969 Chinese women (4146 cases and 1823 controls) the top 49 SNPs that had neither been reported previously nor were in strong linkage disequilibrium with reported SNPs (Stage II). Three SNPs were further evaluated in up to 13 152 Chinese and Japanese women (6436 cases and 6716 controls) (Stage III). Finally, two SNPs were evaluated in 10 847 Korean women (4509 cases and 6338 controls) (Stage IV). SNP rs10822013 on chromosome 10q21.2, located in the zinc finger protein 365 (ZNF365) gene, showed a consistent association with breast cancer risk in all four stages with a combined per-risk allele odds ratio of 1.10 (95% CI: 1.07-1.14) (P-value for trend = 5.87 × 10(-9)). In vitro electrophoretic mobility shift assays demonstrated the potential functional significance of rs10822013. Our results strongly implicate rs10822013 at 10q21.2 as a genetic risk variant for breast cancer among East-Asian women.

• Authors: Qiuyin Cai, Jirong Long, Wei Lu, Shimian Qu, Wanqing Wen, Daehee Kang, Ji-Young Lee, Kexin Chen, Hongbing Shen, Chen-Yang Shen, Hyuna Sung, Keitaro Matsuo, Christopher A Haiman, Ui Soon Khoo, Zefang Ren, Motoki Iwasaki, Kai Gu, Yong-Bing Xiang, Ji-Yeob Choi, Sue K Park, Lina Zhang, Zhibin Hu, Pei-Ei Wu, Dong-Young Noh, Kazuo Tajima, Brian E Henderson, Kelvin Y K Chan, Fengxi Su, Yoshio Kasuga, Wenjing Wang, Jia-Rong Cheng, Keun-Young Yoo, Jong-Young Lee, Hong Zheng, Yao Liu, Ya-Lan Shieh, Sung-Won Kim, Jong Won Lee, Hiroji Iwata, Loic Le Marchand, Sum Yin Chan, Xiaoming Xie, Shoichiro Tsugane, Min Hyuk Lee, Shenming Wang, Guoliang Li, Shawn Levy, Bo Huang, Jiajun Shi, Ryan Delahanty, Ying Zheng, Chun Li, Yu-Tang Gao, Xiao-Ou Shu, Wei Zheng
• Journal: Human molecular genetics (Hum Mol Genet) Vol. 20 Issue 24 Pg. 4991-9 (Dec 15 2011) ISSN: 1460-2083 [Electronic] England
• PMID: 21908515 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Topics

• Adult
• Aged
• Alleles
• Asia
• Breast Neoplasms (genetics)
• Cell Line, Tumor
• Chromosomes, Human, Pair 10 (genetics)
• Female
• Genetic Predisposition to Disease
• Genome-Wide Association Study
• Humans
• Menopause (genetics)
• Middle Aged
• Odds Ratio
• Polymorphism, Single Nucleotide (genetics)