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.