Sequence variations in the DNA repair gene XPD and risk of lung cancer in a chinese population
Sequence variations in the DNA repair gene XPD and risk of lung cancer in a chinese population
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DOI：
10.1002/ijc.11136
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发表时间：
2003-07-10
影响因子：
6.4
通讯作者：
Lin, DX
中科院分区：
文献类型：
--
作者：
Liang, G;Xing, DY;Lin, DX
DNA修复能力的变化被认为在很大程度上由遗传特征决定，与某些癌症的风险有关。着色性干皮病互补D组（XPD）基因Asp 312 Asn和Lys 751 Gin多态性可能改变DNA修复能力。因此，我们通过在中国人中进行的一项大型医院病例对照研究，验证了这2个XPD多态性与肺癌风险相关的假设。研究对象包括1,006名原发性肺癌患者和1,020名年龄和性别匹配的对照人群。使用PCR-RFLP技术确定XPD基因型，并通过无条件逻辑回归计算的比值比（OR）及其95%置信区间（CI）来估计基因型与肺癌风险之间的关联。与312 Asp/Asp基因型纯合子受试者相比，312 Asn/Asn基因型纯合子受试者患肺癌的风险增加（校正OR = 10.33，95%CI = 1.29-8230）。与751 Lys/Lys基因型相比，751 Gln/Gln基因型也与癌症风险增加相关（校正OR = 2.71，95%CI = 1.01-7.24）。分层分析显示，风险增加主要限于肺鳞状细胞癌，312 Asn/Asn基因型的OR为2030（95%CI = 2.25-179.05），751 Gln/Gln基因型的OR为4.24（95%CI = 1.34-13.38）。单倍型分析表明，这些多态性可能与不同的致病基因座连锁不平衡，或与XPD基因座内或附近的其他功能变体一起起作用。
Variation in DNA repair capacity, which is believed to be largely determined by genetic traits, is linked to risk of certain cancers. The Asp312Asn and Lys751Gin polymorphisms in the xeroderma pigmentosum complementary group D (XPD) gene may alter DNA repair capacity. We thus examined the hypothesis that these 2 XPD polymorphisms are associated with risk of lung cancer via a large hospital-based, case-control study among Chinese. The study subjects consisted of 1,006 patients with primary lung cancer and 1,020 age- and sex-matched population controls. XPD genotypes were determined using PCR-RFLP techniques, and the associations between genotypes and risk of lung cancer were estimated by odds ratios (ORs) and their 95% confidence intervals (CIs) calculated by unconditional logistic regression. Subjects homozygous for the 312Asn/Asn genotype had an increased risk of lung cancer (adjusted OR = 10.33, 95% CI = 1.29-8230) compared with subjects homozygous for the 312Asp/Asp genotype. The 751Gln/Gln genotype was also associated with increased risk for the cancer compared with the 751Lys/Lys genotype (adjusted OR = 2.71, 95% CI = 1.01-7.24). Stratification analysis revealed that the increased risk was mainly confined to lung squamous cell carcinoma, with the ORs being 2030 (95% CI = 2.25-179.05) for the 312Asn/Asn genotype and 4.24 (95% CI = 1.34-13.38) for the 751Gln/Gln genotype, respectively. Haplotype analysis with the 2 polymorphisms suggested these polymorphisms might be in linkage disequilibrium with a different causative locus or act together with other functional variants in or close to the XPD locus.