The association between RAD18 Arg302Gln polymorphism and the risk of human non-small-cell lung cancer
The association between RAD18 Arg302Gln polymorphism and the risk of human non-small-cell lung cancer
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DOI：
10.1007/s00432-007-0272-3
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发表时间：
2008-02-01
影响因子：
3.6
通讯作者：
Shimizu, Kenji
中科院分区：
文献类型：
--
作者：
Kanzaki, Hirotaka;Ouchida, Mamoru;Shimizu, Kenji
目的修复酶RAD 18在从酵母到人类的多种生物体的复制后修复过程中起着关键作用，并阐明了RAD 18蛋白的分子功能。已知RAD 18上第302位密码子精氨酸（Arg，CGA）或谷氨酰胺（Gln，CAA）的单核苷酸多态性（SNP）;然而，SNP与任何人类癌症（包括非小细胞肺癌（NSCLC））风险之间的关联尚未报道。本研究旨在探讨该基因多态性与非小细胞肺癌发生、发展的关系。方法选取159例非小细胞肺癌患者和200例健康对照者作为研究对象。采用聚合酶链反应-对向双引物（PCR-CTPP）法对SNP进行基因分型。结果非小细胞肺癌患者Gln/Gln基因型频率（20.7%）显著高于健康对照组（11.5%）（P = 0.003）;携带Gln/Gln基因型的NSCLC患者的风险增加[比值比（OR）= 2.63，95%可信区间（CI）=1.38-4.98]。RAD 18基因Gln/Gln单核苷酸多态性与非小细胞肺癌（NSCLC）的临床病理参数相关性分析显示，RAD 18基因Gln/Gln单核苷酸多态性与肺癌的发病风险显著相关（OR = 4.40，95%CI = 1.60-12.1）。这是第一份报告，以提供证据的RAD 18 Arg 302 Gln多态性和人类非小细胞肺癌的风险之间的关联。
Purpose The repair enzyme RAD18 plays a key role in the post-replication repair process in various organisms from yeast to human, and the molecular function of the RAD18 protein has been elucidated. Single nucleotide polymorphism (SNP) of arginine (Arg, CGA) or glutamine (Gln, CAA) at codon 302 is known on RAD18; however, the association between the SNP and the risk of any human cancers including non-small-cell lung cancer (NSCLC) has not been reported. We therefore investigated the relationship between the polymorphism and the development and progression of human NSCLC.Methods The study population included 159 patients with NSCLC and 200 healthy controls. The SNP was genotyped by polymerase chain reaction with the confronting two-pair primer (PCR-CTPP) assay. Genotype frequencies were compared between patients and controls, and the association of genotypes with clinicopathological parameters was also studied.Results The Gln/Gln genotype was significantly more frequent in NSCLC patients (20.7%) than in healthy controls (11.5%)(P = 0.003). The increased risk was detected in NSCLC patients with the Gln/Gln genotype [Odds ratio (OR) = 2.63, 95% confidence interval (CI)=1.38-4.98]. As to the relationship of the SNP with clinicopathological parameters of NSCLC, significantly higher risks were detected in lung squamous cell carcinoma (LSC) (OR = 4.40, 95% CI = 1.60-12.1).Conclusions Our results suggested that Gln/Gln genotype of the RAD18 SNP has the increased risk of NSCLC, especially of LSC. This is the first report to provide evidence for an association between the RAD18 Arg302Gln polymorphism and human NSCLC risk.