title: Human RAD 17 Polymorphism at Codon 546 Is Associated with the Risk of Colorectal Cancer.
abstract: Human RAD17 acts as an activator of checkpoint signals in response to DNA damage. Here we evaluated the association of hRAD17 Leu546Arg (rs1045051), a missense single nucleotide polymorphism, with the risk of colorectal cancer (CRC) in relation to smoking and alcohol consumption habits in 212 CRC patients and 1,142 cancer-free controls in a case-control study conducted in Japan. The results showed that the hRAD17 Leu/Arg genotype compared to the Leu/Leu genotypes was significantly associated with the protective effect on CRC risk with the adjusted odds ratio (OR) of 0.68 [95% confidence interval (CI): 0.49-0.95, p=0.024], and the males with the Arg/Arg genotype had a greater risk of CRC compared to those with the Leu/Leu and Leu/Arg genotypes (OR=1.87, 95%CI 1.03-3.40, p=0.04). In stratified studies, the protective effect of the Leu/Arg genotype on CRC risk was markedly higher in the light smokers (< 20 pack years) (OR=0.61, 95%CI 0.40-0.94, p=0.024) and the rectal cancer patients (OR=0.49, 95%CI 0.31-0.78, p=0.003). The risk of the Arg/Arg genotype was associated with heavy smoking (≥ 20 pack-years) (OR=2.24, 95%CI 1.09-4.61, p=0.03). These findings suggest that the genetic variant of hRAD17 Leu546Arg polymorphism has a significant effect on CRC susceptibility in Japanese.
authors.affiliation: Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Yasuda
authors.forename: Akiko
authors.initials: A
authors.lastname: Sakai
authors.forename: Sachio
authors.initials: S
authors.lastname: Ito
authors.forename: Kaori
authors.initials: K
authors.lastname: Sasai
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Nagahide
authors.initials: N
authors.lastname: Matsubara
authors.forename: Mamoru
authors.initials: M
authors.lastname: Ouchida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Katayama
authors.forename: Kenji
authors.initials: K
authors.lastname: Shimizu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking / Q000009:adverse effects*; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D003062:Codon; D015179:Colorectal Neoplasms / Q000209:etiology / Q000235:genetics*; D016001:Confidence Intervals; D004249:DNA Damage; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D018797:Cell Cycle Proteins; D003062:Codon; C113575:Rad17 protein, human
keywords: DNA damage; colorectal cancer; human RAD 17; single nucleotide polymorphism