Abstract 1342: Genetic variations in the MUC16 gene encoding tumor marker CA125 and their association with the risk of epithelial ovarian cancer.

Abstract

Abstract Purpose: MUC16 is a cell surface mucin that is expressed at high levels by epithelial ovarian tumors, and is detected in serum as the CA125 antigen. MUC16 is clinically used as a tumor marker in the management of ovarian cancer and has been associated with prognosis. MUC16 is also thought to play an important role in ovarian tumor cell survival and metastasis. We studied the association of four tagging SNPs of the MUC16 gene (rs2547065 (C/G), rs1559168 (A/T), rs2121133 (A/G), rs2121133 (A/G)) and risk of ovarian cancer as well as the correlation of these SNPs with CA125 levels. Methods: MUC16 polymorphisms were genotyped using blood samples collected from 760 women diagnosed with ovarian cancer and 788 healthy controls enrolled in the New England Case-Control Study between 2003 and 2008. 388 cases had preoperative CA125 levels abstracted from medical records. Odds ratios and 95%CIs were calculated using logistic regression; polytomous (multinomial) logistic regression was used to estimate multivariate odds ratios by ovarian cancer histological subtype. The association between log normalized pre-operative CA125 levels and MUC 16 SNPs was evaluated using generalized linear models. Results: A significant association was observed between the rs2547065 polymorphism and ovarian cancer risk (per allele: OR=1.30, 95% CI: 1.11-1.52). The risk was greatest for women carrying two copies of the variant allele (OR=1.78, 95% CI: 1.29-2.45). When stratified by histological subtype, these associations were most apparent in the recessive model for women with serous invasive (OR = 1.69; 95%CI: 1.15-2.48) and clear cell (2.49 95% CI: 1.13-5.52) tumors. There were no significant associations between the other three MUC16 SNPs (rs1559168, rs2121133, rs12984471) and ovarian cancer risk. The rs2547065 polymorphism was not found to be associated with pre-operative CA125 levels in cases overall or in the subset of women with serous and clear cell cancers. Conclusions: These results suggest that women who carry one or more variant alleles of MUC16 SNP rs2547065 have an increased risk of ovarian cancer of the serous invasive and clear cell histological subtype. Further study of MUC 16 SNPs in relation to risk of ovarian cancer and their effect on CA125 levels is warranted. Citation Format: Kristina Williams, Kathryn Terry, Allison Vitonis, Daniel Cramer. Genetic variations in the MUC16 gene encoding tumor marker CA125 and their association with the risk of epithelial ovarian cancer. [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 1342. doi:10.1158/1538-7445.AM2013-1342