Abstract 4846: Genetic variants in the Wnt/beta-catenin signaling pathway as indicators of ovarian cancer risk and survival.

Abstract

Abstract Ovarian cancer is the ninth most common cancer in women and the fifth leading cause of cancer death in 2012. Much is known about the correlation between BRCA mutations and ovarian cancer, but less is known about the impact of common, germline genetic variants on ovarian cancer risk and clinical outcomes. The Wnt/beta-catenin pathway has major roles in regulation of stem cells and other cellular pathways and has been shown to be involved in the development of several different cancers. Therefore, we examined 434 Single Nucleotide Polymorphisms (SNPs) in the Wnt/beta-catenin pathway in 339 ovarian cancer cases and 349 controls. These variants were then assessed for association with risk and clinical outcomes of ovarian cancer. Sixteen polymorphisms had a statistically significant association with ovarian cancer risk with the most significant association being for rs11668593 in APC2 under the dominant model [odds ratio (OR)=0.61; 95% confidence interval (CI), 0.44-0.83]. Unfavorable analysis showed a highly significant cumulative effect of these 16 SNPs on risk (P for trend = 4.22x10−15). In the clinical outcomes analysis, there were eight SNPs that showed an association with ovarian cancer survival. The most significant association with survival was seen for rs11054760 in LRP6 [OR=2.16; 95% CI, 1.33-3.50] which resulted in a poorer survival in patients carrying the heterozygous or homozygous variant genotypes compared to those with the homozygous common genotype. Individuals with the common genotype for rs11054760 had a longer median survival time of 52.7 months compared to only 25.9 months for those with variant containing genotypes (Plog-rank = 3.54x10−4). A gene-dosage effect with a decrease in survival as the number of unfavorable genotypes increased was evident (P for trend = 4.57x10−9). These results implicate genetic variation in the Wnt/beta-catenin signaling pathway as having an impact on risk and clinical outcomes of ovarian cancer. Citation Format: Jeanne A. Pierzynski, Michelle AT Hildebrandt, Xifeng Wu, Karen H. Lu, Dong Liang. Genetic variants in the Wnt/beta-catenin signaling pathway as indicators of ovarian cancer risk and survival. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4846. doi:10.1158/1538-7445.AM2013-4846