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Polymorphisms of XPG/ERCC5 and risk of squamous cell carcinoma of the head and neck.

机译：XPG / ERCC5的多态性和头颈部鳞状细胞癌的风险。

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OBJECTIVES: Xeroderma pigmentosum group G (XPG) protein is essential for the nucleotide excision repair system, and genetic variations in XPG/ERCC5 that affect DNA repair capacity may contribute to the risk of tobacco-induced cancers, including squamous cell carcinoma of the head and neck (SCCHN). We investigated the association between XPG/ERCC5 polymorphisms and risk of SCCHN. METHODS: We genotyped 12 tagging and potentially functional single nucleotide polymorphisms (SNPs) of XPG/ERCC5 in a case-control study of 1059 non-Hispanic white patients with SCCHN and 1066 cancer-free age- and sex-matched controls, and evaluated their associations with the risk of SCCHN. RESULTS: Multivariate logistic regression showed that only an intronic tagging SNP (rs4150351A/C) of XPG/ERCC5 was associated with a decreased risk of SCCHN (adjusted odds ratio=0.76, 95% confidence interval=0.62-0.92 for AC vs. AA; adjusted odds ratio=0.81, 95% confidence interval=0.67-0.98 for AC/CC vs. AA), but this association was nonsignificant after corrections by the permutation test (empirical P=0.105). In the genotype-phenotype correlation analysis using peripheral lymphocytes from 44 patients with SCCHN, we found that rs4150351 AC/CC was associated with a statistically significant increase in the XPG/ERCC5 mRNA expression. CONCLUSION: These findings suggest that genetic variation in XPG/ERCC5 may not affect the risk of SCCHN, although rs4150351 C variant genotypes were associated with an increased expression of XPG/ERCC5 mRNA and nonsignificantly decreased risk of SCCHN. Larger population-based and additional functional studies are warranted to validate our findings.
机译：目的：色皮干燥菌G（XPG）蛋白对于核苷酸切除修复系统必不可少，而且影响DNA修复能力的XPG / ERCC5基因变异可能会导致烟草诱发的癌症，包括头部和头部鳞状细胞癌脖子（SCCHN）。我们调查了XPG / ERCC5多态性与SCCHN风险之间的关联。方法：我们对1059名非西班牙裔SCCHN白人患者和1066名无年龄和性别匹配的对照的病例对照研究中，对XPG / ERCC5的12个标签和潜在功能性单核苷酸多态性（SNP）进行了基因分型，并评估了他们的与SCCHN风险相关。结果：多因素logistic回归分析显示，只有内含标签的SNP（rs4150351A / C）XPG / ERCC5与SCCHN的风险降低相关（AC与AA的校正比值比= 0.76，95％置信区间= 0.62-0.92）。调整后的优势比= 0.81，AC / CC与AA的95％置信区间= 0.67-0.98），但是在通过排列检验校正后，这种关联不显着（经验P = 0.105）。在使用44例SCCHN患者的外周血淋巴细胞的基因型与表型相关性分析中，我们发现rs4150351 AC / CC与XPG / ERCC5 mRNA表达的统计学显着增加相关。结论：这些发现表明，尽管rs4150351 C变异基因型与XPG / ERCC5 mRNA的表达增加和SCCHN风险的降低无关，但XPG / ERCC5的遗传变异可能不会影响SCCHN的风险。有必要进行更大范围的基于人群的研究和其他功能研究，以验证我们的发现。

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