Significant association of the EXO1 rs851797 polymorphism with clinical outcome of ovarian cancer

Abstract

Tingyan Shi,1,2 Rong Jiang,1 Pan Wang,1 Yuan Xu,2 Sheng Yin,1 Xi Cheng,3 Rongyu Zang1,3 1Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Zhongshan Hospital, Fudan University, 2Cancer Institute, 3Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, China Background: Exonuclease 1 (EXO1), one of DNA mismatch repair pathway genes, functions in maintaining genomic stability and affects tumor progression. We hypothesized that genetic variations in EXO1 may predict clinical outcomes in epithelial ovarian cancer (EOC). Methods: In this cohort study with 1,030 consecutive EOC patients, we genotyped four potentially functional polymorphisms in EXO1 by the Taqman assay and evaluated their associations with patients’ survival. Results: Using multivariate Cox proportional hazards regression models, we found that rs851797AG/GG genotypes were significantly associated with recurrence and cancer death (HR =1.30 and 1.38, 95% CI =1.11–1.52 and 1.02–1.88, respectively). Kaplan–Meier survival estimates showed that patients who carried rs851797AG/GG genotypes had poorer progression-free survival and poorer overall survival, compared with rs851797AA genotype carriers (log-rank test, P=0.002 and 0.025, respectively). Moreover, patients with older age at menophania, advanced stage tumor, or being received incomplete cytoreduction were more likely to be recurrent and dead. Conclusion: EXO1 rs851797 polymorphism can predict the clinical outcomes in EOC patients. In addition, age at menophania, FIGO stage, and complete cytoreduction might be independently prognostic factors of ovarian cancer. Large studies with functional experiments are warranted to validate these findings. Keywords: EXO1, ovarian cancer, polymorphism, prognosis

Keywords

• EXO1
• ovarian cancer
• polymorphism
• prognosis