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

Abstract

BackgroundExonuclease 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).MethodsIn 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.ResultsUsing 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.ConclusionEXO1 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.

Differentially expressed genes and key molecules of BRCA1/2-mutant breast cancer: evidence from bioinformatics analyses

“…EXO1, a DNA mismatch repair gene, its polymorphisms have been reported to play a critical role in the development of many tumors (Shi et al, 2017;Zhang et al, 2016). Also, due to its role in DNA replication repair and homology-directed repair, the relationships of EXO1 and BRCA1/2 mutations and its underlying mechanism have become an important focus to be studied (Lemacon et al, 2017).…”

Polymorphisms in DNA mismatch repair pathway genes predict toxicity and response to cisplatin chemoradiation in head and neck squamous cell carcinoma patients

“…Variations in toxicity and response to therapy and/or in survival were seen in patients with lung [ 8 – 11 ], pancreatic [ 12 ], breast [ 13 , 14 ], laryngeal [ 15 ], cervical [ 16 ], and ovarian [ 17 ] cancer treated with CDDP-based schemes and/or RT, which were attributed to abnormalities in production or function of proteins encoded by single nucleotide polymorphisms (SNPs) in genes of MMR pathway. In fact, variant “A”, “G”, “A”, and “A” alleles of MLH1 c.-93G>A (rs1800734) [ 18 ], MSH2 c.211+9C>G (rs2303426) [ 19 ], MSH3 c.3133G>A (rs26279) [ 20 ], and EXO1 c.1765G>A (rs1047840) [ 21 ], reduce levels of expressed protein compared with respective wild-type alleles, and have reduced DNA repair as consequence.…”

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“…Variations in toxicity and response to therapy and/ or in survival were seen in patients with lung [8][9][10][11], pancreatic [12], breast [13,14], laryngeal [15], cervical [16], and ovarian [17] cancer treated with CDDPbased schemes and/or RT, which were attributed to abnormalities in production or function of proteins encoded by single nucleotide polymorphisms (SNPs) in genes of MMR pathway. In fact, variant "A", "G", "A", and "A" alleles of MLH1 c.-93G>A (rs1800734) [18], MSH2 c.211+9C>G (rs2303426) [19], MSH3 c.3133G>A (rs26279) [20], and EXO1 c.1765G>A (rs1047840) [21], reduce levels of expressed protein compared with respective wild-type alleles, and have reduced DNA repair as consequence.…”