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Background: The genes RAD51, XRCC2 and XRCC3 encode proteins that are important for the repair of double-strand DNA breaks by homologous recombination. Therefore, genetic variability in these genes may contribute to the occurrence and progression of endometrial cancer. Methods: The subject of investigation in the reported study was the distribution of genotypes and the prevalence of alleles of the RAD51 G135C, XRCC2 Arg188His and XRCC3 Thr241Met polymorphism in 230 cases of sporadic endometrial cancer; the polymorphisms were determined by polymerase chain reaction-restriction fragment-length polymorphism methods. Results: The obtained results demonstrated a significant positive association between the RAD51 C/C genotype and endometrial carcinoma, with an adjusted odds ratio (OR) of 3.75 ( P < 0.0001). The homozygous C/C genotype was found in 72% of endometrial cancer cases and in 19% of the used controls. The variant 135C allele of RAD51 increased the cancer risk (OR = 1.64 [1.28-2.10] P < 0.0001). There were no significant differences between the distribution of G135C, Arg188His and Thr241Met genotypes in the subgroups assigned to histological grades. Conclusions: The obtained results indicate that the polymorphism of RAD51, but not of either XRCC2 or XRCC3 genes, may be positively associated with the incidence of endometrial carcinoma in the population of Polish women. Further studies, including those on a larger group of patients, are required to further clarify this point. [ABSTRACT FROM AUTHOR]

Abstract: Genetic variations in DNA repair genes may affect an individual''s susceptibility to head and neck cancer. We performed a case–control study to test the association between head and neck cancer risk and two polymorphisms: the C722T of the XRCC3 and the G135C of the RAD51 —genes of DNA double strand break (DSB) repair by homologous recombination (HRR). Genotypes were determined by PCR-restriction fragment lenght polymorphism (PCR-RFLP). DNA was isolated from peripheral blood lymphocytes of agroup of 288 patients consisting of 97 subjects with precancerous hyperplastic laryngeal lesions (PHLL) and 191 subjects with head and neck squamous cell carcinoma (HNSCC) as well as 353 healthy control donors. We found an association between PHLL and the 722CT (OR 6.67; 95% CI 3.02–14.74) as well as 722TT (OR 4.65; 95% CI 2.30–9.43) variants of the XRCC3 gene. Similar relation was observed between these genotypes and HNSCC (OR 2.59; 95% CI 1.61–4.16 and OR 5.54; 95% CI 3.22–9.52, respectively). Moreover, we also observed an association between PHLL (OR 6.04; 95% CI 3.69–9.90) and HNSCC (OR 6.04; 95% CI 3.69–9.90) and the135GC variant of the RAD51 gene. The gene–gene interaction between XRCC3 and RAD51 polymorphic variants may contribute to higher prevalence of PHLL. The increased risk of this disease was observed in case of the combination of the 722CT/135GC (OR 3.81; 95% CI 1.55–9.75) as well as the 722TT/135GC genotypes (OR 5.33; 95% CI 1.96–14.47). The presence of the same genes combinations plays a part in higher probability of HNSCC occurrence (OR 2.42; 95% CI 1.22–4.79 for 722CT/135GC and OR 3.63; 95% CI 1.69–7.76 for 722TT/135GC). We also found an association between these XRCC3 or RAD51 polymorphic variants and smoking status in PHLL (ORs 2.85–10.28 and 1.82–7.35, respectively) and HNSCC patients (ORs 2.94–13.93 and 1.36–3.94, respectively) as well as alcohol intake among PHLL (ORs 3.44–6.12 and 3.52–8.43, respectively) and HNSCC subjects (ORs 2.71–7.01 and 2.33–4.62, respectively). In conclusion our data showed that the C722T and the G135C polymorphisms of the XRCC3 and the RAD51 genes might be associated with HNSCC. Finally we suggested that these polymorphisms might be used as predictive factor of precancerous lesion for head and neck cancer in a Polish population. [Copyright &y& Elsevier]