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Carcinogenesis Advance Access published online on December 6, 2005
Carcinogenesis, doi:10.1093/carcin/bgi282
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© The Author 2005. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org
Received September 12, 2005
Revised October 19, 2005
Accepted November 20, 2005

MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

A gene-gene interaction between ALDH2 Glu487Lys and ADH2 His47Arg polymorphisms regarding the risk of colorectal cancer in Japan

Keitaro Matsuo 1 *, Kenji Wakai 1, Kaoru Hirose 1, Hidemi Ito 1, Toshiko Saito 1, Takeshi Suzuki 2, Tomoyuki Kato 3, Takashi Hirai 3, Yukihide Kanemitsu 3, Hiroshi Hamajima 4, and Kazuo Tajima 1

1 Division of Epidemiology and Prevention, Aichi Cancer Center, Nagoya, Japan
2 Division of Epidemiology and Prevention, Aichi Cancer Center, Nagoya, Japan; Department of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Science, Nagoya
3 Department of Gastroenterological Surgery, Aichi Cancer Center, Nagoya, Japan
4 Department of Clinical Laboratory, Aichi Cancer Center, Nagoya, Japan

* To whom correspondence should be addressed.
Keitaro Matsuo, E-mail: kmatsuo{at}aichi-cc.jp


  Abstract

Alcohol consumption is recognized as a potential risk factor for colorectal cancer (CRC). Genetic polymorphisms, aldehyde dehydrogenase (ALDH2) Glu487Lys and alcohol dehydrogenase 2 (ADH2) His47Arg, which have a strong impact on alcohol metabolism, are common in Japanese population but their significance for CRC carcinogenesis remains to be clarified in detail. We therefore conducted a matched case-control study with 257 incident CRC cases and 771 non-cancer controls at Aichi Cancer Center, including analysis of gene-environment interaction between polymorphisms, drinking and folate consumption. The ADH2 Arg allele was found to be associated with increased risk, the odds ratios (ORs) being 1.35 (95% confidence interval: 1.00-1.84) and 1.93 (1.06-3.53) for the His/Arg and Arg/Arg genotypes, respectively. In contrast, no apparent links were observed with the ALDH2 genotypes. Individuals having ALDH2 Glu/Glu with ADH2 Arg+, ALDH2 Lys+ with ADH2 His/His and ALDH2 Lys+ with ADH2 Arg+ showed ORs of 0.10(0.04-0.21), 0.10 (0.06-0.19), and 1.36 (0.94-1.97), respectively, compared with ALDH2 Glu/Glu with ADH2 His/His. Statistical gene-gene interaction was significant between the two polymorphisms for the risk of CRC (p<0.001). The impact of ALDH2 Lys+ with ADH2 Arg+ was more evident in low folate consumer (OR=2.32, 1.19-4.55) than high folate consumer (OR 1.38, 0.80-2.38). In conclusion, while we failed to find any significant association with the ALDH2 polymorphism itself, significant interaction between ALDH2 and ADH2 polymorphism was observed. Replication in the future study is warranted.

Keywords: colorectal cancer; drinking; gene-environment interaction; ALDH2; ADH2.
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