Abstract 4669: Genetic variations in telomere pathway genes and ovarian cancer risk, survival and treatment response

Abstract

Abstract Telomere dysfunction has been associated with genomic instability and cancer development. Genetic variations in telomere pathway genes may lead to telomere dysfunction and affect cancer risk and outcome. In this retrospective study, we evaluated the associations between common genetic variations in telomere pathway genes and ovarian cancer risk, survival and treatment response in a population of 417 cases and 417 controls. 472 single nucleotide polymorphisms (SNPs) were selected from 42 genes potentially influencing telomere length, telomerase activity, and telomere-associated protein complex. Twenty SNPs were associated with overall ovarian cancer risk at P < 0.01. Two synonymous SNPs from the TEP1 gene, rs938887 and rs2228026, exhibited the strongest association with odds ratios (ORs) of 3.88 (95% CI, 1.42-10.59) and 3.28 (95% CI, 1.72-6.29), respectively. Seven SNPs were associated with overall survival of ovarian cancer at P < 0.01, and five of them presented higher-order gene-gene interactions as suggested by survival tree analysis. Survival tree analysis categorized patients into low, medium and high risk groups with progressively decreased medium survival time based on distinct genotype combinations. In the analysis of response to chemotherapy, 15 SNPs reached a significance level of P ≤ 0.01. SNP rs7826180 in the intronic region of PINX1 gene was shown to substantially increase the risk of poor response with an OR of 6.77 (95% CI, 1.68-27.27). There were significant gene-dosage effects as evidenced by the increased risk of cancer, risk of death, and risk of poor response with the increasing number of unfavorable genotypes. Our results suggest that common genetic variations in telomere pathway genes are significantly associated with ovarian cancer risk, survival, and treatment response. With further validation, these results may contribute to improve personalized risk assessment, prognosis, and treatment of ovarian cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4669. doi:10.1158/1538-7445.AM2011-4669