Association Study Between DNA Repair Pathway Gene Polymorphism And Sensitivity Of Cervical Cancer With Concurrent Chemoradiotherapy

Cervical carcinoma is one of the most common malignant tumor in women, with high morbidity and mortality in developing countries. The current standard treatment of patients with locally advanced cervical cancer is cisplatin-based concurrent chemoradiotherapy (CCRT). Compared to other therapies, CCRT decreased drug toxicity and improved overall survival at the same time. However, owing to genetical characteristics, there remains a subset of patients who showed little response to this therapy.CCRT induces various kinds of DNA lesions and then thereby caused cell cycle arrest and apoptosis in the long run. The anti-tumor ability of CCRT is largely compromised in patients whose tumor cells efficiently repair the induced DNA lesions. As a result, the response rate decreases and clinical outcome is poor. According to a research, DNA repair gene polymorphisms was closely associated with tumor response in non-small cell lung cancer patients receiving chemoradiotherapy. However, no relative research in cervical cancer have been reported. Thus, we aim to reveal potential biomarkers predicting sensitivity of CCRT in patients with cervical cancer by evaluating the association of DNA repair genes polymorphisms and tumor response.In this study, we carried out a retrospective analysis of 72 patients with cervical carcinoma to elucidate associations of 29 SNPs in 25 DNA repair genes with the patients' response to cisplatin-based chemoradiotherapy. We demonstated that the SNP rs9350 in the DNA repair gene Exonuclease 1 (EXO1) was associated with tumor response rate(odds ratio [OR],8.316; 95% CI,2.245-30.807; p=0.002). Furthermore, rs9350 is an independent predictive factor in cervical cancer patients receiving CCRT.