8-Ohdg Repair Is Associated With Platinum Sensitivity In High-Grade Serous Ovarian Carcinoma

Objectives: This study investigated 8-OHdG repair-related gene polymorphisms, 8-OHdG concentration and their association with the risk and survival of high-grade serous ovarian carcinoma (HG-SOC). Methods: Germline variants in the 8-OHdG repair pathway were assessed in 350 sporadic HG-SOC patients (HG-SOCs) and 700 healthy controls. The 8-OHdG concentration in leukocyte DNA was measured by ELISA. Cox proportional hazard models and log-rank test were used to conduct the survival analysis. Results: The genotype and allele frequencies of OGG1 c.977C > G, MUTYH c.972G > C, and TP53 codon 72 Arg/Pro were different to those of platinum-sensitive recurrent HG-SOCs and refractory/platinum-resistant recurrent sub HG-SOCs (P = 0.04, 0.05, and 0.03, respectively). The average value of 8-OHdG/106 dG was higher in patients with OGG1 c.977G, MUTYH c.972G, or TP53 codon 72 Arg alleles (all P < 0.01). High 8-OHdG concentrations in leukocyte DNA was independently associated with shorter overall survival (OS) (P < 0.01) and progression-free survival (PFS) in HG-SOCs. Conclusion: Functional polymorphisms in the base excision repair (BER) system were associated with increased 8-OHdG concentrations and thus with platinum sensitivity and prognosis in HG-SOCs.