The association between RAD18 Arg302Gln polymorphism and the risk of human non-small-cell lung cancer

Hirotaka Kanzaki, Mamoru Ouchida, Hiroko Hanafusa, Hiromasa Yamamoto, Hiromitsu Suzuki, Masaaki Yano, Motoi Aoe, Kazue Imai, Hiroshi Date, Kei Nakachi, Kenji Shimizu

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)211-217
Number of pages7
JournalJournal of Cancer Research and Clinical Oncology
Volume134
Issue number2
DOIs
Publication statusPublished - Feb 2008

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Non-Small Cell Lung Carcinoma
Single Nucleotide Polymorphism
Genotype
Squamous Cell Carcinoma
Odds Ratio
Confidence Intervals
Human Development
Glutamine
Codon
Arginine
Lung Neoplasms
Yeasts
Polymerase Chain Reaction
Lung
Enzymes
Population
Neoplasms
Proteins

Keywords

  • Cancer predisposition
  • Non-small-cell lung cancer (NSCLC)
  • RAD18
  • SNPs

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

The association between RAD18 Arg302Gln polymorphism and the risk of human non-small-cell lung cancer. / Kanzaki, Hirotaka; Ouchida, Mamoru; Hanafusa, Hiroko; Yamamoto, Hiromasa; Suzuki, Hiromitsu; Yano, Masaaki; Aoe, Motoi; Imai, Kazue; Date, Hiroshi; Nakachi, Kei; Shimizu, Kenji.

In: Journal of Cancer Research and Clinical Oncology, Vol. 134, No. 2, 02.2008, p. 211-217.

Research output: Contribution to journalArticle

Kanzaki, Hirotaka ; Ouchida, Mamoru ; Hanafusa, Hiroko ; Yamamoto, Hiromasa ; Suzuki, Hiromitsu ; Yano, Masaaki ; Aoe, Motoi ; Imai, Kazue ; Date, Hiroshi ; Nakachi, Kei ; Shimizu, Kenji. / The association between RAD18 Arg302Gln polymorphism and the risk of human non-small-cell lung cancer. In: Journal of Cancer Research and Clinical Oncology. 2008 ; Vol. 134, No. 2. pp. 211-217.
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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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T1 - The association between RAD18 Arg302Gln polymorphism and the risk of human non-small-cell lung cancer

AU - Kanzaki, Hirotaka

AU - Ouchida, Mamoru

AU - Hanafusa, Hiroko

AU - Yamamoto, Hiromasa

AU - Suzuki, Hiromitsu

AU - Yano, Masaaki

AU - Aoe, Motoi

AU - Imai, Kazue

AU - Date, Hiroshi

AU - Nakachi, Kei

AU - Shimizu, Kenji

PY - 2008/2

Y1 - 2008/2

N2 - 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.

AB - 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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KW - SNPs

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