Carcinogenesis Advance Access published online on July 28, 2005
Carcinogenesis, doi:10.1093/carcin/bgi196
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1 Division of Epidemiology and Prevention, Aichi Cancer Center, Nagoya, Japan
* To whom correspondence should be addressed. One-carbon metabolism, in which folate plays an essential role, is involved in DNA methylation and synthesis and is suspected of impacting on colorectal carcinogenesis. Alcohol is well recognized as a risk factor for colorectal cancer (CRC) and interactions with one-carbon metabolism have also been suggested. Therefore, functional polymorphisms in genes encoding members of this pathway, MTHFR C677T and A1298C, MTR A2756G and TS tandem repeats polymorphisms, have attracted attention. We here conducted a matched case-control study with 257 incident CRC cases and 771 non-cancer controls at Aichi Cancer Center to clarify associations among folate intake and four polymorphisms with reference to CRC risk. Gene-environment interaction between polymorphisms, drinking and folate consumption was also evaluated. None of the polymorphisms showed any significant impact on CRC risk by genotype alone, but when combined with alcohol consumption, the MTHFR 677CC type showed a significantly reduced risk (OR=0.45, 95% confidence interval (CI): 0.23-0.86) (p=0.01). MTR GG showed increased risk only among drinker (OR=3.35, 1.40-8.05) (p=0.047). TS polymorphism did not show statistical significance by genotype alone, while interaction with drinking was significant (p=0.028). The association was not changed even after stratification by daily folate consumption and drinking habit. In conclusion, we found consistently significant interactions between one-carbon metabolism related polymorphisms and alcohol drinking.
Received April 10, 2005
Revised July 19, 2005
Accepted July 22, 2005
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
One-carbon metabolism related gene polymorphisms interact with alcohol drinking to influence the risk of colorectal cancer in 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
3 Department of Gastroenterological Surgery, Aichi Cancer Center, Nagoya, Japan
4 Department of Clinical Laboratory, Aichi Cancer Center, Nagoya, Japan
Keitaro Matsuo, E-mail: kmatsuo{at}aichi-cc.jp
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