Human RAD 17 polymorphism at codon 546 is associated with the risk of colorectal cancer

Yukiko Yasuda, Akiko Sakai, Sachio Itou, Kaori Sasai, Hiromasa Yamamoto, Nagahide Matsubara, Mamoru Oouchida, Hiroshi Katayama, Kenji Shimizu

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)59-68
Number of pages10
JournalActa Medica Okayama
Volume71
Issue number1
Publication statusPublished - 2017

Fingerprint

Polymorphism
Codon
Colorectal Neoplasms
Genotype
Odds Ratio
Confidence Intervals
Smoking
Rectal Neoplasms
Alcohol Drinking
Nucleotides
DNA Damage
Habits
Single Nucleotide Polymorphism
Alcohols
Case-Control Studies
Japan
DNA
Neoplasms

Keywords

  • Colorectal cancer
  • DNA damage
  • Human RAD17
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Human RAD 17 polymorphism at codon 546 is associated with the risk of colorectal cancer. / Yasuda, Yukiko; Sakai, Akiko; Itou, Sachio; Sasai, Kaori; Yamamoto, Hiromasa; Matsubara, Nagahide; Oouchida, Mamoru; Katayama, Hiroshi; Shimizu, Kenji.

In: Acta Medica Okayama, Vol. 71, No. 1, 2017, p. 59-68.

Research output: Contribution to journalArticle

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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.",
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AU - Sakai, Akiko

AU - Itou, Sachio

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AU - Matsubara, Nagahide

AU - Oouchida, Mamoru

AU - Katayama, Hiroshi

AU - Shimizu, Kenji

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