DNA repair gene X-ray repair cross-complementing group 1 and xeroderma pigmentosum group D polymorphisms and risk of prostate cancer: a study from North India

Abstract

Interindividual variation in prostate cancer (PCa) susceptibility may be modulated in part through genetic polymorphisms in the DNA repair genes, especially the genes involved in the base excision repair and nucleotide excision repair pathway. Two of the common single-nucleotide polymorphisms X-ray repair cross-complementing group 1 (XRCC1) and Xeroderma pigmentosum group D (XPD) genes in PCa, which is one of the most common neoplasias in men all over the world, have been studied. In a case-control study of 171 PCa patients and 200 age-matched healthy controls, of similar ethnicity, genotyping was done to determine XPD exon 10 (G23592A), exon 23 (A35931C), and XRCC1 exon 6 (C26304T), exon 9 (G27466A), exon 10 (G23591A) gene polymorphisms by amplification refractory mutation-specific and polymerase chain reaction-restriction fragment length polymorphism methods, respectively. We observed that XPD exon 10 variant AA genotype was associated with increased risk for PCa (adjusted odds ratio [OR] 2.63, 95% confidence interval [95% CI] 1.40-4.92, p = 0.003), and XRCC1 exon 9 GA genotype was also statistically associated with PCa (adjusted OR 2.61, 95% CI 1.53-4.43, p < 0.001). However, XPD exon 23 (A>C) and XRCC1 exon 6 (C>T) and exon 10 (G>A) did not have significantly increased risk for PCa. The haplotype analysis of XPD exon 10 and exon 23 G-C (OR 3.44, 95% CI 2.15-5.51, p < 0.0001) and A-A (OR 4.96, 95% CI 3.08-7.98, p < 0.0001) was associated with a significant increase in PCa risk. Similarly, the combined analysis of XRCC1 exon 6, exon 9, and exon 10 C-G-A (OR 2.93, 95% CI 1.91-4.50, p < 0.001) and C-A-G (OR 2.48, 95% CI 1.62-3.80, p < 0.001) demonstrated statistically significant risk in PCa. XRCC1 exon 9 GA genotype showed protective association with high grade of PCa. Our results suggest a positive association of XRCC1 exon 9 and XPD exon 10 genotypes that may play an important role in the pathophysiology and may modulate the risk of PCa.