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Ann Coloproctol > Volume 24(5); 2008 > Article
Journal of the Korean Society of Coloproctology 2008;24(5):329-336.
DOI: https://doi.org/10.3393/jksc.2008.24.5.329   
Polymorphism of the 5,10-Methylenetetrahydrofolate Reductase (MTHFR) Gene and Microsatellite Instability (MSI) in Mucinous Colorectal Cancer.
Kim, Hae Sol , Kang, Bong Su , Kim, Jong Woo , Ahn, Dae Ho , Bae, Su Jin , Kim, Nam Gun
1Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
2Department of Surgery, College of Medicine, Pochon CHA University, Seongnam, Korea. kjw@cha.ac.kr
3Clinical Medicine Research Center, College of Medicine, Pochon CHA University, Seongnam, Korea.
Abstract
PURPOSE
Generally, a mucinous carcinoma (Muc) of the colon show higher rates of microsatellite instability (MSI) than a non-mucinous carcinoma (non-Muc). Mutated methylenetetrahydrofolate reductase (MTHFR) brings about low enzyme activity, which may reduce genomic DNA methylation. These processes may be critical for the oncogenic transformation of human cells. We compared the relationship of MSI and MTHFR polymorphism in Muc to that in non-Muc.
METHODS
From March 2003 to August 2007, genomic DNA was isolated from whole blood and tissue specimens of 285 colorectal cancer patients (Muc: 31 cases, non-Muc: 254 cases) and 448 normal control patients. These were subjected to MSI analysis and MTHFR genotyping by using PCR-based restriction fragment length polymorphism analyses.
RESULTS
MSI was significantly more frequent in the Muc group (40.7%) than in the non- Muc group (14.8%). The frequencies of polymorphism of MTHFR 677C>T were CC (31.5%), CT (57%), and TT (11.5%) in the patient group and 32.4%, 53.1%, and 14.5% in the control group. In the Muc group, the frequencies of polymorphism of MTHFR 677C>T were CC (36%), CT (56%), TT (8%), and in the non-Muc group, they were 31.1%, 57%, and 11.9%. The frequencies of polymorphism of MTHFR 1298A>C were AA (73%), AC (21.3%), and CC (5.7%) in the patient group and 69.6%, 28.6%, and 1.8% in the control group. In the Muc group, the frequencies of polymorphism of MTHFR 1298A>C were AA (50%), AC (30%), and CC (20%), and in the non-Muc group, they were 76%, 20.3%, and 3.7%. The Muc group showed higher frequencies of the CC variant than the non-Muc group (P-value=0.018). No relation between MSI and MTHFR polymorphisms were seen in any comparison of the Muc and the non-Muc groups.
CONCLUSIONS
The Muc group showed higher rates of MSI than the non-Muc group, but no definite difference between the Muc and the non-Muc groups was noted in the case of polymorphism of MTHFR 677C>T. However, the TT-type variant showed slightly lower frequencies in the Muc group than in the non-Muc group. On the contrary, the Muc group showed a higher rate of the CC variant in polymorphism of MTHFR 1298A>C. These inconsistent results seem to be due to the small size of the Muc group, so further study is needed.
Key Words: Mucinous colorectal cancer; MTHFR polymorphism; MSI


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