Kanzaki Hirotaka, Ouchida Mamoru, Hanafusa Hiroko, Yamamoto Hiromasa, Suzuki Hiromitsu, Yano Masaaki, Aoe Motoi, Imai Kazue, Date Hiroshi, Nakachi Kei, Shimizu Kenji
Department of Molecular Genetics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
J Cancer Res Clin Oncol. 2008 Feb;134(2):211-7. doi: 10.1007/s00432-007-0272-3. Epub 2007 Jul 12.
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.
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.
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).
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.
修复酶RAD18在从酵母到人类的各种生物体的复制后修复过程中起关键作用，并且RAD18蛋白的分子功能已得到阐明。已知RAD18密码子302处存在精氨酸（Arg，CGA）或谷氨酰胺（Gln，CAA）的单核苷酸多态性（SNP）；然而，尚未报道该SNP与包括非小细胞肺癌（NSCLC）在内的任何人类癌症风险之间的关联。因此，我们研究了该多态性与人类NSCLC发生发展的关系。
研究人群包括159例NSCLC患者和200例健康对照。通过聚合酶链反应与双引物对法（PCR-CTPP）对SNP进行基因分型。比较患者和对照之间的基因型频率，并研究基因型与临床病理参数的关联。
NSCLC患者中Gln/Gln基因型的频率（20.7%）显著高于健康对照（11.5%）（P = 0.003）。在具有Gln/Gln基因型的NSCLC患者中检测到风险增加[比值比（OR）= 2.63，95%置信区间（CI）= 1.38 - 4.98]。关于该SNP与NSCLC临床病理参数的关系，在肺鳞状细胞癌（LSC）中检测到显著更高的风险（OR = 4.40，95% CI = 1.60 - 12.1）。
我们的结果表明，RAD18 SNP的Gln/Gln基因型具有增加的NSCLC风险，尤其是LSC。这是首次报道为RAD18 Arg302Gln多态性与人类NSCLC风险之间的关联提供证据。
