TY - JOUR
T1 - Human RAD 17 polymorphism at codon 546 is associated with the risk of colorectal cancer
AU - Yasuda, Yukiko
AU - Sakai, Akiko
AU - Ito, Sachio
AU - Sasai, Kaori
AU - Yamamoto, Hiromasa
AU - Matsubara, Nagahide
AU - Ouchida, Mamoru
AU - Katayama, Hiroshi
AU - Shimizu, Kenji
N1 - Publisher Copyright:
© 2017 by Okayama University Medical School.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - Colorectal cancer
KW - DNA damage
KW - Human RAD17
KW - Single nucleotide polymorphism
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M3 - Article
C2 - 28238011
AN - SCOPUS:85013092918
VL - 71
SP - 59
EP - 68
JO - Acta Medica Okayama
JF - Acta Medica Okayama
SN - 0386-300X
IS - 1
ER -