Methylenetetrahydrofolate reductase gene germ-line C677T and A1298C SNPs are associated with colorectal cancer risk in the Turkish population.

Filiz Ozen,Ozturk Ozdemir,Metin Sen

doi:10.7314/apjcp.2014.15.18.7731

Filiz Ozen, Ozturk Ozdemir + Show 1 more

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https://doi.org/10.7314/apjcp.2014.15.18.7731

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Abstract

Colorectal cancer (CRC) is the third most common cause of death due to cancer in the worldwide and the incidence is also increasing in Turkey. Our present aim was to investigate any association between germ-line methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and CRC risk in Turkey. A total of 86 CRC cases and 212 control individuals of the same ethnicity were included in the current study. Peripheral blood-DNA samples were used for genotyping by StripAssay technique, based on the reverse- hybridization principle and real-time PCR methods. Results were compared in Pearson Chi-square and multiple logistic regression models. The MTHFR 677TT (homozygous) genotype was found in 20.9% and the T allele frequency 4.2-fold increased in CRC when compared with the control group.The second SNP MTHFR 1298CC (homozygous) genotype was found in 14.0% and the C allele frequency 1.4-fold elevated in the CRC group. The current data suggest strong associations between both SNPs of germ-line MTHFR 677 C>T and 1298 A>C genotypes and CRC susceptibility in the Turkish population. Now the results need to be confirmed with a larger sample size.

Highlights

Colorectal cancer is one of the most common types of cancer and the incidence varies and appears to be increasing in worldwide
The methylenetetrahydrofolate reductase (MTHFR) 677TT genotype was found in 20.9% and the T allele frequency 4.2-fold increased in Colorectal cancer (CRC) when compared with the control group.The second SNP MTHFR 1298CC genotype was found in 14.0% and the C allele frequency 1.4-fold elevated in the CRC group
Most of tumour were in grade 2 in the current CRC cohort histopathologically; 9 (10.5) samples were in grade1, 54 (62.8%) samples were in grade 2, 8 (9.3%) samples were in grade 3 and 7(8.1%) samples were in unknown profile (Table 1)

Summary

Introduction

Colorectal cancer is one of the most common types of cancer and the incidence varies and appears to be increasing in worldwide. The folate status in some cases was reported in the CRC risk (Choi et al, 2000; Xu et al, 2004). The methylene tetrahydrofolate reductase (MTHFR) enzyme plays a crucial role in the folate metabolism that catalyzes the irreversible reaction of 5,10-methylene-tetrahydrofolate to 5-methyl tetrahydrofolate, which serves as a substrate for the remethylation of homocysteine to methionine, with the subsequent synthesis of S adenosylmethionine(Friedman et al, 1999; Parle et al, 2006; Slattery et al, 1999; Pardini et al, 2011). The substrate of MTHFR 5,10-methylenetetrahydrofolate, is required for thymidine synthesis via thymidylate synthase, and indirectly for purine biosynthesis(Frosst et al, 1995; Weisberg et al, 1998). Decreasing the MTHFR enzyme function may cause to the global DNA hypomethylation due to lack of the intracelular methyl sources and initiates carcinogenesis process. Decreasing the MTHFR enzyme function may cause to the global DNA hypomethylation due to lack of the intracelular methyl sources and initiates carcinogenesis process. (Blount et al, 1997; Stern et al, 2000; Fang et al, 2003)

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