Single nucleotide polymorphism in the RAD18 gene and risk of colorectal cancer in the Japanese population

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

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14 Citations (Scopus)

Abstract

The RAD18 gene, located on the human chromosome 3p24-p25, plays a crucial role in post-replication repair (PRR) in various organisms from yeast to humans. In the human RAD18 gene, one coding single nucleotide polymorphism (SNP) at codon 302, encoding either arginine (Arg, CGA) or glutamine (Gln, CAA), was reported. Although the molecular function of the RAD18 protein came to be elucidated, the association between the RAD18 Arg302Gln polymorphism and the risk of human cancer development was not examined. Therefore, we investigated the relationship between the polymorphism and the development of human primary colorectal cancer (CRC). The Arg302Gln polymorphism in 100 patients with CRC and 200 healthy controls were genotyped by the polymerase chain reaction with confronting two-pair primer (PCR-CTPP) assay. The Gln/Gln genotype was significantly more frequent in CRC (18.0%) than in the healthy controls (11.5%) (p=0.046). The increased risk was detected in CRC patients with the Gln/Gln genotype (Odds ratio [OR], 2.10; 95% confidence interval [CI], 1.00 to 4.40). When the relationship of the SNP with clinicopathological parameters of CRC was investigated, particularly in the well-differentiated grade and in the lymph node metastasis (N1) CRC patients, significantly higher risks were detected (OR, 7.00; 95% CI, 1.19-41.1 and OR, 3.71; 95% CI, 1.30-10.6, respectively). These results suggested that the RAD18 Arg302Gln polymorphism is associated with the risk of CRC. This report provides evidence for an association between the RAD18 Arg302Gln polymorphism and human CRC risk.

Original languageEnglish
Pages (from-to)1171-1175
Number of pages5
JournalOncology reports
Volume18
Issue number5
Publication statusPublished - Nov 2007

Keywords

  • Cancer predisposition
  • Colorectal cancer
  • Post-replication repair
  • RAD18
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Kanzaki, H., Ouchida, M., Hanafusa, H., Sakai, A., Yamamoto, H., Suzuki, H., Yano, M., Aoe, M., Imai, K., Date, H., Nakachi, K., & Shimizu, K. (2007). Single nucleotide polymorphism in the RAD18 gene and risk of colorectal cancer in the Japanese population. Oncology reports, 18(5), 1171-1175.