The association between RAD18 Arg302Gln polymorphism and the risk of human non-small-cell lung cancer.
OBJECTIVE
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.
Kanzaki
Hirotaka
H
Department of Molecular Genetics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Ouchida
Mamoru
M
Hanafusa
Hiroko
H
Yamamoto
Hiromasa
H
Suzuki
Hiromitsu
H
Yano
Masaaki
M
Aoe
Motoi
M
Imai
Kazue
K
Date
Hiroshi
H
Nakachi
Kei
K
Shimizu
Kenji
K
D000230:Adenocarcinoma / Q000235:genetics / Q000556:secondary; D000368:Aged; D000483:Alleles; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000556:secondary; D016022:Case-Control Studies; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D044767:Ubiquitin-Protein Ligases
D004268:DNA-Binding Proteins; C485954:RAD18 protein, human; D044767:Ubiquitin-Protein Ligases