Abstract 2620: Contribution of risk variant in miR-125b binding site of BMPR1B in women of African ancestry with breast cancer

Abstract

Abstract MicroRNAs play a fundamental role in gene regulation by selective binding to the 3′ UTR of specific mRNAs. Dysregulation of this post-transcriptional regulatory mechanism, in turn, has emerged to be an important process in cancer etiology. Recently a particular single nucleotide polymorphism (SNP) at mir-125b binding locus of BMPR1B, rs1434536, was reported as significant risk factor for breast cancer pathogenesis in Caucasians. The BMPR1B gene encodes a member of the bone morphogenetic protein (BMP) receptor family of transmembrane serine/threonine kinases. The C/T allelic variation within the target site disrupts the regulation of miR-125b, whereby increased BMPR1B expression ultimately elevates disease risk. To validate whether rs1434536 also contributes to breast cancer risk in women of African ancestry, we performed a case-control study of 805 breast cancer cases (422 African Americans (AA) and 383 Nigerians (NG)) and 786 controls (402 AA and 384 NG). The average age (±SD) was 46.9 ± 11.9 years for cases and 45.1 ± 12.4 years for controls. Genotyping was conducted using polymerace chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Test for Hardy-Weinberg equilibrium (HWE) suggested that there was no deviation from HWE (P > 0.05) in AA, or NG. Pearson's chi-squared tests showed that this SNP was significantly associated with breast cancer in AA (p=0.03) but not in NG (p=0.96). After adjusting for age in the logistic regression, we found the heterozygous genotype CT was associated with nearly 30% lower odds of breast cancer compared to CC genotype (OR=0.74, 95% CI 0.55-0.99; p=0.04) in AA. In the pooled analysis adjusting for both age and sites, the CT genotype was not statistically significant (OR=0.85, 95% CI 0.68-1.06; p=0.15). The common allele T (allele frequency = 0.60) was the risk allele in the previous study conducted in Caucasians, whereas the T allele was the minor allele in subjects of African descent (allele frequency = 0.129 in NG and = 0.232 in AA). In conclusion, our preliminary study found the T allele to have a trend for a protective effect in AA, which is disagreement with the observation made in the original study. Thus, this study indicates the need for replication studies in diverse populations to validate whether rs1434536 is a risk variant for specific subtypes of breast cancer. 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 2620. doi:1538-7445.AM2012-2620