The association between RAD18 Arg302Gln polymorphism and the risk of human non-small-cell lung cancer |
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Authors: | Hirotaka Kanzaki Mamoru Ouchida Hiroko Hanafusa Hiromasa Yamamoto Hiromitsu Suzuki Masaaki Yano Motoi Aoe Kazue Imai Hiroshi Date Kei Nakachi Kenji Shimizu |
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Institution: | (1) Department of Molecular Genetics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558, Japan;(2) Department of Cancer and Thoracic Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan;(3) Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation, Hiroshima 732-0815, Japan |
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Abstract: | 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. |
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Keywords: | SNPs RAD18 Non-small-cell lung cancer (NSCLC) Cancer predisposition |
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