TITLE:
Genetic Polymorphisms in ADH1B and ALDH2 Are Associated with Colorectal Tumors in Japan: A Case-Control Study
AUTHORS:
Akiko Shiotani, Hideki Ishikawa, Michihiro Mutoh, Tatsuya Takeshita, Tomiyo Nakamura, Kanehisa Morimoto, Toshiyuki Sakai, Keiji Wakabayashi, Nariaki Matsuura
KEYWORDS:
Genetic Polymorphisms, Colorectal Tumor, Alcohol Intake, Alcohol Dehydrogenase-1B, Aldehyde Dehydrogenase-2
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.6 No.12,
November
12,
2015
ABSTRACT: Background: Unlike with esophageal cancer, acetaldehyde levels and
genetic polymorphisms in alcohol dehydrogenase have not yet been shown to be
contributing factors for colorectal cancer (CRC). This study aimed to clarify
the mechanism of CRC development related to alcohol consumption and to the
presence of genetic polymorphisms in the alcohol dehydrogenase, ADH1B and aldehyde
dehydrogenase, ALDH2. Methods: This was a case-control study (221 cases and 179
controls) in patients with adenomas and intramucosal tumors who underwent
endoscopic removal of all tumors. The amount of alcohol consumption was
determined using a self-recorded questionnaire, and the tumor information was
obtained from colonoscopy results. Blood samples were taken to analyze the
following polymorphisms: ALDH2 Glu504Lys and ADH1B His48Arg. Results: The
polymorphisms in ADH1B and ALDH2 had little influence on the development of
colorectal adenoma or intramucosal cancer. Patients with ALDH2 (Glu/Glu) were
more tolerant of alcohol than those with ALDH2 (Glu/Lys and Lys/Lys). Next, we
examined certain combinations of the ADH1B genotypes. In the ALDH2 (Glu/Glu)
group, an increased risk (OR = 3.4; 95% CI 1.4 - 8.4; P = 0.009) was observed
among moderate/heavy drinkers with ADH1B (His/His). In the ALDH2 (Glu/Lys and
Lys/Lys) group, an increased risk (OR = 4.2; 95% CI 1.1 - 16.7; P = 0.041) was
found among moderate/heavy drinkers with ADH1B (Arg/His and Arg/Arg).
Conclusions: ADH1B and ALDH2 activity may be involved in the development of CRC.