| Objective: Ovarian cancer has the highest mortality rate of all gynecologic cancers.Epithelial ovarian cancer(EOC)is the most common histological type of ovarian cancer.Approximately 70% of patients are diagnosed at an advanced stage(International Federation of Gynecology and Obstetrics,FIGO stage III and IV)due to the lack of effective screening programs in clinical practice,and the 5-year survival rate is only 20% to 40%.The standard treatment for women with advanced stage EOC is surgical cytoreduction followed by platinum-based chemotherapy.Despite initial high response rate to current treatment,most patients relapse within 18 months.Therefore,the identification of effective biomarkers that could help to predict the risk of EOC,drug resistance to chemotherapy and clinical prognosis may significantly improve the survival rate of EOC patients.DNA mismatch repair(MMR)plays a key role in maintaining genomic stability.Published evidence suggests that the individual DNA repair capacity may affect tumor development,progression,and patients’ prognosis.The polymorphisms in DNA repair genes may be associated with altered DNA repair capacity,thereby affecting the risk of carcinogenesis and the clinical prognosis of patients.In this study,we investigated the relationship between hMSH2 gene rs2303428 and hMHL1 gene rs1800734 single nucleotide polymorphisms(SNPs)and the risk of EOC and the clinical outcome of patients in Northern China.Methods: Genomic DNA was extracted from peripheral blood lymphocytes by the proteinase K digestion-saturated sodium chloride salting out method.The genotypes of hMSH2 gene rs2303428 and hMHL1 gene rs1800734 SNPs were detected by the polymerase chain reaction-ligase detection reaction(PCR-LDR).Associations between hMSH2 gene rs2303428 and hMLH1 gene rs1800734 SNPs and the risk of EOC are investigated in a case-control study(536 patients with EOC and 532 control women).A cohort study was conducted to analyze the relationship between hMSH2 gene rs2303428 and hMLH1 gene rs1800734 SNPs and clinical prognosis of EOC patients.All the statistical analyses were performed using the SPSS 22.0 statistical software package(SPSS Company,Chicago,IL,USA).All statistical tests were two-sided,and P values <0.05 were considered statistically significant.Results:(1)There were no significant differences in the genotype(P=0.97)or allele(P=0.88)frequencies of hMSH2 gene rs2303428 polymorphism between case and control group.(2)There were no significant differences in the genotype(P=0.94)or allele(P=0.95)frequencies of hMLH1 gene rs1800734 polymorphism between case and control group.(3)Multivariate analysis of Cox proportional hazard regression model(adjusted for age,stage,grade,histology,and residual tumour size)identified that rs2303428 polymorphism was associated with clinical prognosis in patients with EOC.A significantly increased risk of EOC recurrence was found during the 3-and 5-year follow-up in patients carrying C/T+C/C genotypes,when compared to patients carrying T/T genotype(HR=1.41,95%CI=1.07~1.87;HR=1.56,95%CI=1.12~2.16).(4)Multivariate analysis of Cox proportional hazard regression model(adjusted for age,stage,grade,histology,and residual tumour size)identified that rs1800734 polymorphism was associated with clinical prognosis in patients with EOC.A significantly decreased risk of EOC recurrence was found during the 5-year follow-up in patients carrying A/G+A/A genotypes,when compared to patients carrying G/G genotype(HR=0.66,95 %CI=0.44~0.98).Conclusions:(1)hMSH2 gene rs2303428 and hMLH1 gene rs1800734 SNPs are not associated with the risk of EOC.(2)hMSH2 gene rs2303428 single nucleotide polymorphism is associated with clinical prognosis of EOC patients,the C allele is an independent risk factor for recurrence in patients with EOC.(3)hMLH1 gene rs1800734 single nucleotide polymorphism is associated with clinical prognosis of EOC patients,the A allele is an independent protective factor for recurrence in patients with EOC. |
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