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Impact of the MTHFR C677T polymorphism on colorectal cancer in a population with low genetic variability

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

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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Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. 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 Delgado-Plasencia, Vicente Medina-Arana, Alberto Bravo-Gutiérrez & Julián Pérez-Palma

  2. Servicio de Anatomía Patológica, Hospital Universitario de Canarias, Ofra, s/n. La Cuesta, 38320, La Laguna, Santa Cruz de Tenerife, Islas Canarias, Spain

    Hugo Álvarez-Argüelles

  3. Unidad de Investigación, Hospital Universitario de Canarias, Ofra, s/n. La Cuesta, 38320, La Laguna, Santa Cruz de Tenerife, Islas Canarias, Spain

    Eduardo Salido-Ruiz

  4. Unidad de Genética, Departamento de Biología, Universidad Autónoma de Madrid, Cantoblanco, 28049, Madrid, Spain

    Antonia M. Fernández-Peralta & Juan J. González-Aguilera

  5. 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 Delgado-Plasencia

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  1. Luciano Delgado-Plasencia
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  2. Vicente Medina-Arana
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  5. Hugo Álvarez-Argüelles
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  6. Eduardo Salido-Ruiz
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  8. Juan J. González-Aguilera
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Correspondence to Luciano Delgado-Plasencia.

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Delgado-Plasencia, L., Medina-Arana, V., Bravo-Gutiérrez, A. et al. Impact of the MTHFR C677T polymorphism on colorectal cancer in a population with low genetic variability. Int J Colorectal Dis 28, 1187–1193 (2013). https://doi.org/10.1007/s00384-013-1644-6

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  • DOI: https://doi.org/10.1007/s00384-013-1644-6

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