Department of Urology, The Third Affiliated Hospital of Nantong University, Wuxi, Jiangsu, China.
PLoS One. 2012;7(9):e44756. doi: 10.1371/journal.pone.0044756. Epub 2012 Sep 21.
DNA repair genes (EG: xeroderma pigmentosum group D, XPD) may affect the capacity of encoded DNA repair enzymes to effectively remove DNA adducts or lesions, which may result in enhanced cancer risk. The association between XPD gene polymorphisms and the susceptibility of prostate cancer (PCa) was inconsistent in previous studies.
METHODOLOGY/PRINCIPAL FINDINGS: A meta-analysis based on 9 independent case-control studies involving 3165 PCa patients and 3539 healthy controls for XPD Gln751Lys SNP (single nucleotide polymorphism) and 2555 cases and 3182 controls for Asn312Asp SNP was performed to address this association. Meanwhile, odds ratio (OR) and 95% confidence intervals (CIs) were used to evaluate this relationship. Statistical analysis was performed with STATA10.0. No significant association was found between XPD Gln751Lys SNP and PCa risk. On the other hand, in subgroup analysis based on ethnicity, associations were observed in Asian (eg. Asn vs. Asp: OR = 1.34, 95%CI = 1.16-1.55; Asn/Asn+Asn/Asp vs. Asp/Asp: OR = 1.23, 95%CI = 1.07-1.42) and African (eg. Asn vs. Asp: OR = 1.31, 95%CI = 1.01-1.70; Asn/Asn vs. Asp/Asp: OR = 1.71, 95%CI = 1.03-7.10) populations for Asn312Asp SNP. Moreover, similar associations were detected in hospital-based controls studies; the frequency of Asn/Asn genotype in early stage of PCa men was poorly higher than those in advanced stage of PCa men (OR = 1.45, 95%CI = 1.00-2.11).
CONCLUSION/SIGNIFICANCE: Our investigations demonstrate that XPD Asn312Asp SNP not the Gln751Lys SNP, might poorly increase PCa risk in Asians and Africans, moreover, this SNPs may associate with the tumor stage of PCa. Further studies based on larger sample size and gene-environment interactions should be conducted to determine the role of XPD gene polymorphisms in PCa risk.
DNA 修复基因（例如，着色性干皮病组 D，XPD）可能会影响编码的 DNA 修复酶有效去除 DNA 加合物或损伤的能力，从而导致癌症风险增加。先前的研究中，XPD 基因多态性与前列腺癌（PCa）易感性之间的关联并不一致。
方法/主要发现：我们进行了一项基于 9 项独立病例对照研究的荟萃分析，共纳入 3165 例 PCa 患者和 3539 例健康对照者，用于研究 XPD Gln751Lys SNP（单核苷酸多态性）；纳入 2555 例病例和 3182 例对照者，用于研究 Asn312Asp SNP。同时，使用比值比（OR）和 95%置信区间（CI）来评估这种相关性。统计分析采用 STATA10.0 软件。未发现 XPD Gln751Lys SNP 与 PCa 风险之间存在显著关联。另一方面，基于种族的亚组分析显示，亚洲人群（例如，Asn 对 Asp：OR=1.34，95%CI=1.16-1.55；Asn/Asn+Asn/Asp 对 Asp/Asp：OR=1.23，95%CI=1.07-1.42）和非洲人群（例如，Asn 对 Asp：OR=1.31，95%CI=1.01-1.70；Asn/Asn 对 Asp/Asp：OR=1.71，95%CI=1.03-7.10）中 XPD Asn312Asp SNP 与 PCa 风险相关。此外，我们还在医院对照研究中发现了类似的关联；早期 PCa 男性中 Asn/Asn 基因型的频率明显高于晚期 PCa 男性（OR=1.45，95%CI=1.00-2.11）。
结论/意义：我们的研究表明，XPD Asn312Asp SNP 而非 Gln751Lys SNP 可能会轻微增加亚洲人和非洲人患 PCa 的风险，此外，该 SNP 可能与 PCa 的肿瘤分期相关。应进行基于更大样本量和基因-环境相互作用的进一步研究，以确定 XPD 基因多态性在 PCa 风险中的作用。
