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About half of all prostate cancer (PCa) patients receive radiotherapy (RT) either as single curative treatment or as adjuvant/salvage treatment after radical prostatectomy. However, RT is associated with a spectrum of side effects (toxicity) in the surrounding normal tissues. Acute toxicity occurs within 90 days of treatment, is usually transient and affects skin and mucosa of bladder and intestine resulting in dermatitis, cystitis or diarrhea. XRCC3 gene encodes for protein that is involved in homologous recombination repair of double-strand breaks created by ionizing radiation. Disruption of these pathways has the potential to affect the normal tissue response to RT. The T variant of XRCC3 Thr241Met single nucleotide polymorphisms (SNP) in exon 7 (C>T, rs861539) was reported to be associated with elevated levels of DNA adducts, chromosomal deletions, sensitivity to ionizing radiation and cross-linking agents. The aim of this study was to examine association between this SNP and RT-induced normal tissue toxicity in PCa patients.

Eighty one patients who had a histologically confirmed localized or locally advanced PCa were included in the study. Patients were treated with 3DC RT (n=70) or ARC RT (n=11) with radical (72 Gy)(47 patients) or postoperative/salvage (66 Gy)(34 patients) RT without previous hormonal therapy. DNA from peripheral blood mononuclear cells was extracted by salting out method. XRCC3 Thr241Met SNP was determined by PCR-RFLP analysis. The restriction fragments were separated on 2100 Bioanalyzer using DNA 1000 kit. The differences in the distribution of genotypes of XRCC3 Thr241Met between patients with or without acute RT-induced genitourinary (GU) or gastrointestinal (GI) toxicity were tested by χ2 and Fisher’s exact test. P values ≤ 0.05 were considered statistically significant, while p values between 0.1 and 0.05 were pointed out as a statistical trend. Data were analyzed by SigmaStat 3.5.

The acute GI toxicity appeared in 100%, 94.6% and 81.8% of ThrThr, ThrMet and MetMet PCa patients, raspectivelly. There was the statistical trend towards higher acute GU toxicity in carriers of Thr variant (ThrThr plus ThrMet) vs. MetMet (p=0.087) as well as ThrThr vs. MetMet (p=0.058). For acute GI toxicity, there was a similar distribution in genotypes: 90.9%, 91.9%, 90.9% for ThrThr, ThrMet, MetMet, respectively. PCa patients with ThrThr genotype had higher rate of acute GU toxicity grade ≥2 (45.5%) than ThrMet (28.6%) and MetMet (22.2%) while in GI toxicity MetMet had higher rate of grade ≥2 (40%) than ThrThr (23.3%) and ThrMet (23.5%) but without statistical significance.

The obtained data indicate that Thr variant of XRCC3 Thr241Met SNP is related to acute GU toxicity. Grade ≥2 acute GU toxicity could be associated with ThrThr while GI toxicity with MetMet genotype. Further study on larger group is necessary to confirm this date and to clarify mechanism underlying this observation.