Based on these results, the XRCC1-Arg399Gln polymorphism might be a risk factor for PCa and it could be considered as a prognostic and predictive biomarker for susceptible men.
Overall, the results of this meta-analysis show that the XRCC1-Arg399Gln polymorphism may be associated with an increased risk for prostate cancer under the homozygote model and the recessive model.
We examined the association between PC risk with nonsynonymous SNPs (nsSNPs) in 5 genes involved in 3 DNA-repair pathways: (1) base excision repair (BER): hOGG1 C1245G (Ser326Cys) and XRCC1 G28152A (Arg399Gln); (2) nucleotide excision repair (NER): XPD G23591A (Asp312Asn); (3) homologous recombination repair: RAD51 G135C (in 5' untranslated region) and XRCC3 C18067T (Thr241Met).
Haplotype analysis of XRCC1 Arg194Trp (C/T) and Arg399Gln (G/A) revealed that the frequency of the T-A haplotype was significantly higher in PC patients.
Among the three polymorphisms, we found that the XRCC1 Arg399Gln variant allele was associated with increased PCa risk (adjusted odd ratio [OR]: 1.67, 95% confident interval [CI]: 1.11-2.51), but the XRCC1 Arg194Trp variant allele had a 38% reduction in risk of PCa (adjusted OR: 0.62, 95% CI: 0.41-0.93).
We found that the XRCC1-Arg399Gln AA and the MGMT-Leu84Phe CT+TT genotypes were associated with an increased risk of prostate cancer [odds ratio (OR), 2.18; 95% confidence interval (CI), 0.99-4.81 and OR, 1.99; 95% CI, 1.19-3.34, respectively].
To determine whether the XRCC1 (codon Arg399Gln) and XPD (codon Asp312Asn and codon Lys751Gln) polymorphisms are associated with prostate cancer susceptibility, we genotyped these polymorphisms in a primarily Caucasian sample of 506 sibships (n = 1,117) ascertained through a brother with prostate cancer.