Hypermethylation of RAD51L3 and XRCC2 genes to predict late toxicity in chemoradiotherapy-treated cervical cancer patients.

ABSTRACT

Cervical cancer affects women worldwide, especially in developing countries. Approximately 500,000 cases of this disease are diagnosed per year. The method of choice in the treatment of advanced cervical cancers (in accordance with the International Federation of Gynecology and Obstetrics staging system (FIGO) starting from stage IIB) is combined radiotherapy with concomitant chemotherapy. This treatment provides good tumour control, but it carries a risk of late complications in the irradiated area in 10-15 % of cases. Methylation is one of the methods of epigenetic control, which has an important role in gene expression. Aberrant methylation of normal CpG islands in promoters of tumour suppressor genes such as RB, p53 or DNA reparation genes ATM, BRCA1,2, and RAD51 gene family causes silencing of their function and cell cycle deregulation, which is one of the efficient ways of neoplastic transformation. The significantly decreased expression of molecules involved in DNA response may cause facilitated radiosensitivity in predisposed individuals. We looked for the relationship between hypermethylation of 18 DNA reparation genes and late toxicity occurrence in cervical cancer patients treated by chemoradiotherapy using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). The cut-off value for the hypermethylation was set at 10 %. We confirmed significant association between promoter hypermethylation in the XRCC2 gene and occurrence of late grade III-IV toxicity in cervical cancer patients (P = 0.0357). This finding could be useful in the late toxicity prediction in radiotherapy-treated patients.