Abstract 1659: Evaluation of microRNA expression profiles and their associations with risk alleles in lymphoblastoid cell lines of familial ovarian cancer

Abstract

Abstract Interindividual variations of microRNA expression are likely to influence the expression of microRNA target genes, and therefore, contribute to phenotypic differences in humans, including cancer susceptibility. Whether microRNA expression variation has any role in ovarian cancer development is still unknown. Here we evaluated microRNA expression profiles in lymphoblastoid cell lines (LCLs) from 74 women with familial ovarian cancer and 47 controls. We found that microRNA expression profiles in the LCLs of the cases were significantly different from that in the controls with 91% accuracy by 95 differentially expressed microRNAs. To assess the potential implications of microRNAs in ovarian cancer, we investigated the associations between microRNA expression and ovarian cancer risk alleles discovered from genome wide association studies. We observed 130 significant associations at a permutation level of 0.01. Compared to other risk variants, rs3814113 and rs2072590 had the greatest number of significant associations (68 and 37, respectively). Interestingly, 14 microRNAs which were associated with ovarian cancer risk alleles belong to 5 microRNA clusters. The most notable cluster is the tumorigenic miR-17-92 cluster with 5 microRNAs, all of which are significantly associated with rs3814113. Using pathway analysis, several key biological pathways were significantly overrepresented, such as cellular response to stress (P=2.87x10−06), etc. Our results indicate that microRNA expression profiles in LCLs can serve as potential detection biomarkers for familial ovarian cancer. Further characterization of significant associations between microRNAs and risk alleles could facilitate the understanding of the functions of these GWAS discovered risk alleles in the genetic etiology of ovarian 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 1659. doi:1538-7445.AM2012-1659