Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
DNA Cell Biol. 2010 Apr;29(4):183-90. doi: 10.1089/dna.2009.0956.
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.
个体间前列腺癌（PCa）易感性的差异可能部分受到 DNA 修复基因中遗传多态性的调节，特别是涉及碱基切除修复和核苷酸切除修复途径的基因。X 射线修复交叉互补组 1（XRCC1）和着色性干皮病组 D（XPD）是 PCa 中两个常见的单核苷酸多态性，XPD 基因位于 PCa 中，是全世界男性中最常见的肿瘤之一，对其进行了研究。在一项针对 171 名 PCa 患者和 200 名年龄匹配的健康对照者的病例对照研究中，通过扩增受阻突变特异性聚合酶链反应-限制性片段长度多态性方法，分别对 XPD 外显子 10（G23592A）、外显子 23（A35931C）和 XRCC1 外显子 6（C26304T）、外显子 9（G27466A）、外显子 10（G23591A）进行基因分型。我们观察到 XPD 外显子 10 变体 AA 基因型与 PCa 风险增加相关（调整后的优势比[OR]2.63，95%置信区间[95%CI]1.40-4.92，p=0.003），XRCC1 外显子 9 GA 基因型也与 PCa 统计学相关（调整后的 OR 2.61，95%CI 1.53-4.43，p<0.001）。然而，XPD 外显子 23（A>C）和 XRCC1 外显子 6（C>T）和外显子 10（G>A）与 PCa 风险无显著增加。XPD 外显子 10 和外显子 23 G-C（OR 3.44，95%CI 2.15-5.51，p<0.0001）和 A-A（OR 4.96，95%CI 3.08-7.98，p<0.0001）的单体型分析与 PCa 风险显著增加相关。类似地，XRCC1 外显子 6、外显子 9 和外显子 10 C-G-A（OR 2.93，95%CI 1.91-4.50，p<0.001）和 C-A-G（OR 2.48，95%CI 1.62-3.80，p<0.001）的联合分析显示与 PCa 风险具有统计学意义。XRCC1 外显子 9 GA 基因型与高级别 PCa 具有保护相关性。我们的结果表明，XRCC1 外显子 9 和 XPD 外显子 10 基因型之间存在正相关，可能在病理生理学中发挥重要作用，并可能调节 PCa 的风险。
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