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Impact of the MTHFR C677T polymorphism on colorectal cancer in a population with low genetic variability.
MedLine Citation:
PMID:  23422951     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Luciano Delgado-Plasencia; Vicente Medina-Arana; Alberto Bravo-Gutiérrez; Julián Pérez-Palma; Hugo Alvarez-Argüelles; Eduardo Salido-Ruiz; Antonia M Fernández-Peralta; Juan J González-Aguilera
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-2-20
Journal Detail:
Title:  International journal of colorectal disease     Volume:  -     ISSN:  1432-1262     ISO Abbreviation:  Int J Colorectal Dis     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-2-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8607899     Medline TA:  Int J Colorectal Dis     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Servicio de Cirugía General y Digestiva, Hospital Universitario de Canarias, Ofra, s/n. La Cuesta, 38320, La Laguna, Santa Cruz de Tenerife, Islas Canarias, Spain, luciano_delgado1@yahoo.es.
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