Abstract 1647: Evaluation of breast cancer susceptibility loci in Chinese women from Singapore

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Genome-wide association studies (GWAS) have identified several breast cancer susceptibility loci associated with European populations, some of which were also found to be associated with breast cancer among women in China. Women in Singapore are predominantly of Chinese ancestry with an urbanized lifestyle, with breast cancer rates approaching those of the West. To explore the role of these breast cancer susceptibility variants, a Taqman-based microfluidics strategy was established to carry out fast track replication of 22 SNPs for 1,146 cases and 1,534 controls to identify significant risk variants for breast cancer. Interestingly, the most significant SNP [rs2046210; odds ratio (OR), 1.4; 95% confidence interval, 1.2-1.6; P=7x10−6], residing in 6q25.1, had been initially identified in a Chinese population, suggesting a strong and consistent association of this SNP with Chinese ancestry. SNPs in FGFR2 (rs2981579, rs1219648, rs2981582, rs112000014), 8q24 (rs13281615), and MAP3K1 (rs16886165) showed significant associations similar to those observed in women of European ancestry, with ORs ranging from 1.1 to 1.7 (P=5x10−5 to 0.04). Ranking of the SNPs in terms of their ORs for Singaporean Chinese women was compared to that from Western and Chinese studies. The ranking for Singaporean Chinese women resembled, but was not identical to, that of women in China, reflecting the effect of ethnicity. Comprehensive annotation of the genotyping data with associated clinicopathological features enabled the identification of significant SNPs associated with tumour size, lymph node metastasis, and estrogen/progesterone receptor status. Findings from this study implicate 6q25.1 and FGFR2 as the most important susceptibility loci for Asian women of Chinese ancestry and may guide future fine-mapping studies to identify causal variants. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1647. doi:1538-7445.AM2012-1647