Polymorphisms in the XPG gene and risk of gastric cancer in Chinese populations
Polymorphisms in the XPG gene and risk of gastric cancer in Chinese populations
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XPG基因多态性与中国人群胃癌风险
DOI：
10.1007/s00439-012-1152-8
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发表时间：
2012-07-01
期刊：
影响因子：
5.3
通讯作者：
Li, Jin
中科院分区：
文献类型：
--
作者：
He, Jing;Qiu, Li-Xin;Li, Jin
DNA修复基因在维持基因组DNA的稳定性和完整性方面起着重要作用。核苷酸切除修复基因的多态性可能导致DNA修复能力表型的变化，从而导致癌症风险。在这项包含1,125例胃癌患者和1,196例无癌对照的病例对照研究中，我们研究了着色性干皮病G组（XPG）基因的三种功能性单核苷酸多态性（SNPs，rs 2296147 T> C，rs 2094258 C> T和rs 873601 G> A）与胃癌风险之间的关系。我们使用Taqman分析对这三种SNP进行基因分型，并使用逻辑回归模型估计比值比（OR）和95%置信区间（95%CI）。我们发现只有rs 873601 A变异基因型与胃腺癌的显著高风险相关（AA vs. GG的校正OR = 1.30，95%CI = 1.03-1.64，AA vs. GG/AG的校正OR = 1.23，95%CI = 1.01-1.49）。分层分析表明，这种风险在老年（> 59岁）、男性、既往吸烟者和NGCA患者亚组中更为明显。而rs 2296147 T> C和rs 2094258 C> T两个单核苷酸多态性位点均未检测到。然后，我们对141例患者的胃癌癌旁正常组织进行了表达分析，发现A变异等位基因与XPG mRNA表达的非显著降低相关（P（趋势）= 0.107）。使用来自HapMap的mRNA表达数据的进一步分析表明，A等位基因与45名中国人（P（趋势）= 0.003）以及261名不同种族受试者（P（趋势）= 0.001）的正常细胞系中XPG mRNA表达显著降低相关。这些支持了功能性XPG变体可能有助于胃癌风险的假设。需要对不同种族人群进行更大规模的研究来验证我们的发现。
DNA repair genes play an important role in maintaining stability and integrity of genomic DNA. Polymorphisms in nucleotide excision repair genes may cause variations in DNA repair capacity phenotype and thus contribute to cancer risk. In this case-control study of 1,125 gastric cancer cases and 1,196 cancer-free controls, we investigated the association between three functional single nucleotide polymorphisms (SNPs, rs2296147T > C, rs2094258C > T and rs873601G > A) in the xeroderma pigmentosum group G (XPG) gene and gastric cancer risk. We used the Taqman assays to genotype these three SNPs and logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). We found that only the rs873601A variant genotypes were associated with a significant higher risk for gastric adenocarcinoma (adjusted OR = 1.30, 95% CI = 1.03-1.64 for AA vs. GG and adjusted OR = 1.23, 95% CI = 1.01-1.49 for AA vs. GG/AG). Stratification analysis indicated that this risk was more pronounced in subgroups of older age (> 59 years), males, ever-smokers, and patients with NGCA. All these were not found for the other two SNPs (rs2296147T > C and rs2094258C > T). We then performed expression analysis using gastric cancer adjacent normal tissues from 141 patients and found that the A variant allele was associated with non-significantly reduced expression of XPG mRNA (P (trend) = 0.107). Further analysis using mRNA expression data from the HapMap suggested that the A allele was associated with significantly reduced expression of XPG mRNA in normal cell lines for 45 Chinese (P (trend) = 0.003) as well as for 261 subjects with different ethnicities (P (trend) = 0.001). These support the hypothesis that functional XPG variants may contribute to the risk of gastric cancer. Larger studies with different ethnic populations are warranted to validate our findings.