Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and colorectal cancer: The Fukuoka Colorectal Cancer Study

Guang Yin, Suminori Kono, Kengo Toyomura, Tomoko Hagiwara, Jun Nagano, Tetsuya Mizoue, Ryuichi Mibu, Masao Tanaka, Yoshihiro Kakeji, Yoshihiko Maehara, Takeshi Okamura, Koji Ikejiri, Kitaroh Futami, Yohichi Yasunami, Takafumi Maekawa, Kenji Takenaka, Hitoshi Ichimiya, Nobutoshi Imaizumi

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Abstract

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme regulating folate metabolism, which affects DNA synthesis and methylation. This study investigated the relation of MTHFR C677T and A1298C polymorphisms to colorectal cancer in a case-control study in Fukuoka, Japan. The subjects comprised 685 incident cases of histologically confirmed colorectal adenocarcinomas and 778 community controls selected randomly in the study area. The genotype was determined by the PCR-RFLP method using genomic DNA extracted from buffy coat. Alcohol use was ascertained by in-person interview. Statistical adjustment was made for gender, age class, area, and alcohol use. The MTHFR 677TT genotype was associated with a statistically significant decrease in the risk with an adjusted odds ratio of 0.69 (95% confidence interval 0.51-0.93) compared with the 677CC and 677CT combined, and the decrease was most evident in individuals with no alcohol consumption. While the A1298C polymorphism showed no measurable association with the overall risk of colorectal cancer, the 1298CC genotype was associated with a statistically significant increase in the risk when alcohol consumption was high, and was also associated with an approximately 2-fold increase in the risk of each of proximal and distal colon cancer. The findings add to evidence that individuals with the MTHFR 677TT genotype have a decreased risk of colorectal cancer in the absence of folate depletion, suggesting a protective role of folate by ensuring a sufficient thymidylate pool for DNA synthesis. Because very few individuals had the 1298CC genotype, the findings regarding the A1298C polymorphism need careful interpretation and confirmation in larger studies.

Original languageEnglish
Pages (from-to)908-913
Number of pages6
JournalCancer Science
Volume95
Issue number11
DOIs
Publication statusPublished - Nov 1 2004

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Yin, G., Kono, S., Toyomura, K., Hagiwara, T., Nagano, J., Mizoue, T., Mibu, R., Tanaka, M., Kakeji, Y., Maehara, Y., Okamura, T., Ikejiri, K., Futami, K., Yasunami, Y., Maekawa, T., Takenaka, K., Ichimiya, H., & Imaizumi, N. (2004). Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and colorectal cancer: The Fukuoka Colorectal Cancer Study. Cancer Science, 95(11), 908-913. https://doi.org/10.1111/j.1349-7006.2004.tb02201.x