Li Su-Xia, Dai Qiang-Sheng, Chen Su-Xiu, Zhang Shao-Dan, Liao Xiao-Yu, Deng Xia, Chi Hong-Bo, Li Feng-Jie, Zhu Jin-Hong, Jiang Yi-Yan
Department of Tumor Rehabilitation, First Hospital, Wenzhou Medical University, No.2 Fuxue Lane, Wenzhou, Zhejiang, 325000, China.
Tumour Biol. 2014 Apr;35(4):3905-15. doi: 10.1007/s13277-013-1519-z. Epub 2013 Dec 18.
Numerous epidemiological studies have been conducted to investigate the association between Xeroderma pigmentosum complementation group D (XPD) Asp312Asn (rs1799793 G > A) and Lys751Gln (rs13181 A > C) polymorphisms and bladder cancer risk; however, the conclusions remain controversial. With this in mind, we performed this meta-analysis with 11 studies including 3,797 cases and 5,094 controls for Asp312Asn and 21 studies including 6,360 cases and 7,894 controls for Lys751Gln polymorphism. We searched available literatures from PubMed, Embase, and CBM databases. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of the associations. Moreover, to validate biological plausibility of our findings, the effects of these two polymorphisms on XPD gene expression within three ethnicities was determine by gene expression analysis based on imputed genotypes from HapMap. Overall, the variant allele of Asp312Asn polymorphism was associated with an increased risk of bladder cancer (Asn/Asn vs. Asp/Asp: OR = 1.51, 95% CI = 1.19-1.91; Asp/Asn vs. Asp/Asp: OR = 1.23, 95% CI = 1.12-1.35; recessive model: OR = 1.33, 95% CI = 1.10-1.61; dominant model: OR = 1.32, 95% CI = 1.14-1.52; and allele comparing: OR = 1.26, 95% CI = 1.11-1.42). We found the Lys751Gln was associated with increased bladder cancer risk only under the recessive model (OR = 1.14, 95% CI = 1.01-1.29). Stratification analyses demonstrated an increased risk for Asians and hospital-based studies under all genetic models while only under the dominant model for Caucasians as to the Asp312Asn polymorphism and for Caucasians under the recessive model as to the Lys751Gln polymorphism. We also found the Asp312Asn polymorphism can significantly influence mRNA expression levels among Asians and Caucasians, and the Lys751Gln polymorphism has a similar effect for Caucasians. Despite some limitations, this meta-analysis suggests that polymorphisms in XPD gene may contribute to bladder cancer susceptibility. These findings need further validation by large well-designed prospective studies.
已开展了大量流行病学研究，以调查着色性干皮病互补组D（XPD）Asp312Asn（rs1799793 G＞A）和Lys751Gln（rs13181 A＞C）多态性与膀胱癌风险之间的关联；然而，结论仍存在争议。考虑到这一点，我们进行了这项荟萃分析，其中包括11项研究（3797例病例和5094例对照）用于分析Asp312Asn，以及21项研究（6360例病例和7894例对照）用于分析Lys751Gln多态性。我们检索了来自PubMed、Embase和中国生物医学文献数据库（CBM）的现有文献。计算了粗比值比（OR）和95%置信区间（CI），以评估关联强度。此外，为了验证我们研究结果的生物学合理性，基于HapMap的推算基因型，通过基因表达分析确定了这两种多态性对三个种族中XPD基因表达的影响。总体而言，Asp312Asn多态性的变异等位基因与膀胱癌风险增加相关（Asn/Asn与Asp/Asp比较：OR = 1.51，95% CI = 1.19 - 1.91；Asp/Asn与Asp/Asp比较：OR = 1.23，95% CI = 1.12 - 1.35；隐性模型：OR = 1.33，95% CI = 1.10 - 1.61；显性模型：OR = 1.32，95% CI = 1.14 - 1.52；等位基因比较：OR = 1.26，95% CI = 1.11 - 1.42）。我们发现Lys751Gln仅在隐性模型下与膀胱癌风险增加相关（OR = 1.14，95% CI = 1.01 - 1.29）。分层分析表明，对于Asp312Asn多态性，亚洲人和基于医院的研究在所有遗传模型下风险增加，而对于白种人仅在显性模型下风险增加；对于Lys751Gln多态性，白种人在隐性模型下风险增加。我们还发现Asp312Asn多态性可显著影响亚洲人和白种人的mRNA表达水平，Lys751Gln多态性对白种人有类似影响。尽管存在一些局限性，但这项荟萃分析表明XPD基因多态性可能与膀胱癌易感性有关。这些发现需要通过大规模精心设计的前瞻性研究进一步验证。
