Carcinogenesis Advance Access published online on March 24, 2005
Carcinogenesis, doi:10.1093/carcin/bgi076
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1 Department of Epidemiology, Huaxi Public Health School, Sichuan University, Chengdu 610041, China; Division of Epidemiology and Prevention, Aichi Cancer Center, Nagoya, Japan
* To whom correspondence should be addressed. Folate takes part in two biological pathways involved in DNA methylation and synthesis and a potential protective influence of this nutrient chemical against carcinogenicity has been recognized in several sites, including the esophagus. Therefore, the functional polymorphisms in genes encoding folate metabolizing enzymes, MTHFR C677T and MTR A2756G, might be suspected of impacting on esophageal cancer risk. We therefore conducted a matched case-control study of 165 esophageal cancer cases and 495 non-cancer controls to clarify associations among folate intake, MTHFR C677T and MTR A2756G polymorphisms and esophageal cancer risk. Gene-environment interactions between the two polymorphisms and drinking and smoking were also evaluated. Folate consumption and MTHFR 677TT were associated with a non-significant tendency for decreased risk while the MTR genotypes did not show any links in themselves; further, when analysis was limited to heavy drinkers, the MTHFR TT genotype significantly decreased esophageal cancer risk (odds ratio (OR)=0.27, 95% confidence interval (CI): 0.09-0.76). The OR for the gene-environment interaction between heavy drinking and the 677TT genotype in the case-only design was 0.31 (0.10-0.94), indicating risk with heavy drinking to be 69% decreased in individuals harboring the 677TT genotype. We failed to find any significant interaction between either of the polymorphisms and smoking.
Received January 16, 2005
Revised March 4, 2005
Accepted March 16, 2005
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Gene-environment interactions between alcohol drinking and the MTHFR C677T polymorphism impact on esophageal cancer risk: results of a case-control study in Japan
2 Division of Epidemiology and Prevention, Aichi Cancer Center, Nagoya, Japan
3 Department of Rehabilitation Service, Aichi Cancer Center, Nagoya, Japan
4 Department of Thoracic Surgery, Aichi Cancer Center, Nagoya, Japan
5 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
6 Department of Clinical Laboratory, Aichi Cancer Center, Nagoya, Japan
Keitaro Matsuo, E-mail: kmatsuo{at}aichi-cc.jp
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