Association Between Key Genes Of Non-homologous End Joining Pathway And Response To Concurrent Chemoradiotherapy In Squamous Cell Cervical Carcinoma

Squamous cell cervical carcinoma (SCC) is the most common types of cervical cancer and threat the health of female individuals. At present, concurrent chemoradiotherapy (CCRT), cisplatin-based chemotherapy concurrent with radiotherapy, has been used as the standard treatment for locally advanced carcinoma of the cervix in clinical setting. Patients treated with CCRT have a longer survival time and less toxic effects, when compared to those received radiation therapy alone or other treatments. However, a part of patients still failed to benefit from it. Therefore, identifying molecular markers which can predict the response to CCRT is very important for clinical treatment of SCC.Impact of CCRT on DNA or DNA metabolic processes can induce DNA double strand break (DSB) directly or indirectly and then trigger the death of tumor cells. NHEJ pathway can repair DSB in mammalian cells, so the function of NHEJ is closely related to the sensitivity to radiation or chemoradiotherapy. Many studies have reported that the mRNA expression levels and single nucleotide polymorphisms (SNPs) of genes involved in NHEJ pathway including XRCC4, XRCC5, XRCC6, LIG4, PRKDC and DCLRE1C can affect cells sensitivity to radiotherapy or chemotherapy.A cohort of 42 pre-treatment biopsies obtained from SCC was included. The mRNA levels of 6 genes listed in NHEJ pathway were analyzed by realtime PCR, and the association between mRNA levels and the response of CCRT were further investigated. The results showed that, the response rate was 47.6% in patients with high XRCC6 mRNA expression level and 90.5% in patients with low mRNA expression level of XRCC6 (P=0.003); No statistically association was found between the response rate and the mRNA expression level of each of the rest five genes. Then, the association between genetic polymorphisms of XRCC6 (rs2267437) and CCRT was analyzed. There was no significant association between the rs2267437 genetic polymorphisms and response rate. The expression of XRCC6 mRNA could be used as a predictive molecular marker in the clinical treatment of SCC patients receiving CCRT.