Association between single nucleotide polymorphisms in the gene for XRCC1 and radiation-induced late toxicity in prostate cancer patients

Abstract

Background and purposePolymorphisms in genes responsible for DNA damage signaling and repair might modulate DNA repair capacity and, therefore, affect cell and tissue response to radiation and influence individual radiosensitivity. The purpose of the present prospective investigation was to evaluate the association of single nucleotide polymorphisms in XRCC1 with radiation-induced late side effects in prostate cancer patients treated with radiotherapy. Material and methodsTo analyze the role of XRCC1 polymorphisms for late toxicity 603 participants from the Austrian PROCAGENE study treated with three-dimensional conformal radiotherapy were included in the present investigation. Three non-synonymous candidate polymorphisms in the X-ray repair cross-complementing group 1 (XRCC1) gene (Arg194Trp; Arg280His; Arg399Gln) were selected and determined by 5´-nuclease (TaqMan) assays. ResultsWithin a median follow-up time of 35months, 91 patients (15.7%) developed high-grade late toxicities (defined as late bladder and/or rectal toxicity RTOG⩾2). In a Kaplan–Meier analysis, carriers of the XRCC1 Arg280His polymorphism were at decreased risk of high-grade late toxicity (p=0.022), in multivariate analysis including clinical and dosimetric parameters as potential confounders the XRCC1 Arg280His polymorphism remained a significant predictor for high-grade late toxicity (HR=0.221, 95% CI 0.051–0.956; p=0.043). No significant associations were found for the remaining polymorphisms. ConclusionsWe conclude that the XRCC1 Arg280His polymorphism may be protective against the development of high-grade late toxicity after radiotherapy in prostate cancer patients.