期刊
HUMAN MOLECULAR GENETICS
卷 20, 期 24, 页码 4991-4999出版社
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddr405
关键词
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资金
- US National Institutes of Health [R01CA124558, R01CA064277, R37CA070867, R01CA090899, R01CA100374]
- Ingram Professorship
- Research Reward funds
- Department of Defense (DOD) [BC011118, BC050791]
- Shanghai Breast Cancer Study [R01CA064277]
- Shanghai Breast Cancer Survival Study [R01CA118229]
- Shanghai Endometrial Cancer Study [R01CA092585]
- Seoul Breast Cancer Study (Basic Research Laboratory (BRL)) through the National Research Foundation of Korea
- Ministry of Education, Science and Technology [2011-0001564]
- Korean Hereditary Breast Cancer Study/Korean Genome and Epidemiology Study (Ministry for Health, Welfare and Family Affairs, Republic of Korea) [1020350]
- Tianjin Study (National Natural Science Foundation of China) [30771844]
- Nanjing Study (Jiangsu, China) [09KJA330001]
- Taiwan Biobank Study [DOH97-01]
- Hong Kong Study (Research Grant Council, Hong Kong SAR, China) [HKU 7520/05M, 76730M]
- Guangzhou Breast Cancer Study (National Natural Science Foundation of China) [81072383]
- Multiethnic Cohort Study [CA063464, CA054281, CA132839]
- Nagano Breast Cancer Study (Ministry of Health, Labor and Welfare of Japan) [17015049, H20-002]
- Nagano Breast Cancer Study (Ministry of Education, Culture, Sports, Science, and Technology of Japan) [221S0001]
- Vanderbilt-Ingram Cancer Center [P30 CA068485]
- [R01CA122756]
- Grants-in-Aid for Scientific Research [17015049] Funding Source: KAKEN
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 x 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.
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