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New Breast Cancer Risk Variant Discovered at 10q25 in East Asian Women

Background: Recently, 41 new genetic susceptibility loci for breast cancer risk were identified in a genome-wide association study (GWAS) conducted in European descendants. Most of these risk variants have not been directly replicated in Asian populations. Methods: We evaluated nine of those nonreplication loci in East Asians to identify new risk variants for breast cancer in these regions. First, we analyzed single-nucleotide polymorphisms (SNP) in these regions using data from two GWAS conducted among Chinese and Korean women, including 5,083 cases and 4,376 controls (stage 1). In each region, we selected an SNP showing the strongest association with breast cancer risk for replication in an independent set of 7,294 cases and 9,404 controls of East Asian descents (stage 2). Logistic regression models were used to calculate adjusted ORs and 95% confidence intervals (CI) as a measure of the association of breast cancer risk and genetic variants. Results: Two SNPs were replicated in stage 2 at P < 0.05: rs1419026 at 6q14 [per allele OR, 1.07; 95% confidence interval (CI), 1.03–1.12; P = 3.0 × 10−4] and rs941827 at 10q25 (OR, 0.92, 95% CI, 0.89–0.96; P = 5.3 × 10−5). The association with rs941827 remained highly statistically significant after adjusting for the risk variant identified initially in women of European ancestry (OR, 0.88; 95% CI, 0.82–0.97; P = 5.3 × 10−5). Conclusion: We identified a new breast cancer risk variant at 10q25 in East Asian women. Impact: Results from this study improve the understanding of the genetic basis for breast cancer. Cancer Epidemiol Biomarkers Prev; 22(7); 1297–303. ©2013 AACR.