Abstract LB-370: Fine mapping of 32 breast cancer risk loci in women of East Asian ancestry

Abstract

Abstract Background: Genome-wide association studies (GWAS) have identified multiple genetic susceptibility loci for breast cancer risk. The majority of these loci, however, were identified in studies conducted in European descendants. A comprehensive evaluation of these risk loci using densely genotyped data in East Asians may help to identify independent association signals and risk variants that are more closely related to breast cancer risk in East Asian women than those reported initially. Methods: We performed a fine-scale mapping of 32 breast cancer susceptibility loci identified in previous GWAS in 5,703 breast cancer cases and 5,766 controls in studies conducted in Shanghai, China, Nearly 4,100 variants in these 32 loci were genotyped. We imputed genotypes using the 1000 Genomes Project (Phase 3) as the reference. Included in this analysis were 4,086 genotyped and more than 17,000 well-imputed common variants. At each locus, analyses using logistic regression models were conducted to identify variants that better capture the association with breast cancer risk and new risk variants that are not correlated with the risk variants reported from the initial studies (index SNPs). To identify additional independent risk variants, logistic regression conditional on the most significantly associated variant was performed. Results: We identified risk variants that better captured the association than the index SNPs at 3 loci (2q35, rs1478596, OR = 1.14, P = 5.6×10-6; 6q25.1, rs9322344, OR = 0.89, P = 3.1×10-5;11q24.3, rs11221769, OR = 1.12, P = 6.1 ×10-5), new risk variants at 2 loci (1p13.2, rs3789614, OR = 1.31, P = 0.002; 2q31.1, rs117055746, OR = 0.87, P = 0.004), and independent risk variants at two loci (6q14.1, rs200626240, OR = 0.89, P = 0.001; 6q25.1 rs2982684, OR = 0.87, P = 2.7×10-5, Chr6:152107810, OR = 0.91, P = 1.4×10-4). Conclusion: This study identified multiple risk variants that were more relevant to East Asians than the index SNPs. These risk variants combined explained a further 2% of the familial relative risk in this population. This study highlighted the need of fine-mapping studies in non-European ancestral populations to search for additional risk variants. Citation Format: Chenjie Zeng, Qiuyin Cai, Jirong Long, Ying Zheng, Yong-Bing Xiang, Jiajun Shi, Xiao-Ou Shu, Wei Zheng. Fine mapping of 32 breast cancer risk loci in women of East Asian ancestry. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-370.