Journal
INTERNATIONAL JOURNAL OF COLORECTAL DISEASE
Volume 28, Issue 9, Pages 1187-1193Publisher
SPRINGER
DOI: 10.1007/s00384-013-1644-6
Keywords
Colorectal cancer risk; MTHFR C677T polymorphism; Survival; 5-FU-based chemotherapy
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Purposes Methylenetetrahydrofolate reductase (MTHFR) plays a key role in folate metabolism, and folate is implicated in carcinogenesis by its role in DNA methylation, repair, and synthesis. We analyzed the impact of MTHFR C677T polymorphism in colorectal cancer in a region of the Tenerife Island whose population has a history of genetic isolation and a low genetic variability. This allows analyzing the effects of the polymorphism that are not due to interactions with different genetic variants. Methods Genomic DNA of 50 Spanish sporadic colorectal cancer (CRC) patients and 103 controls was analyzed by PCR/RFLP and sequencing. Results The T allele is more frequent in controls than in patients (P<0.01). The variant (T) carriers displayed significant odds ratio values for the CT heterozygotes (P=0.026) and even when grouping heterozygote (CT) and homozygotes (TT) (P=0.015). Patients carriers of the variant T (CT y TT) show a higher survival rate after chemotherapy than the CC homozygotes (log rank; P=0.001). Conclusions The MTHRF C677T variant has a protective effect on CRC development in a population with low allelic variability and an optimal intake of folic acid. Moreover, patients carrying the variant (T) show a better prognosis after 5-fluorouracil/folinic acid-based chemotherapy.
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