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Colorectal cancer and polymorphism of methylenetetrahydrofolate reductase (C677T) in Morocco

Cancer colorectal et polymorphisme du méthylènetétrahydrofolate réductase (C677T) au Maroc

  • Original Article / Article Original
  • Published:
Journal Africain du Cancer / African Journal of Cancer

Abstract

Introduction

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism. It is involved in the synthesis, repair, and methylation of deoxyribonucleic acid (DNA). The most frequently studied MTHFR gene polymorphism is C677T, which is involved in the pathogenesis of many diseases including cancer. This case-control study was undertaken to analyze the association of MTHFR C677T polymorphism and the risk of colorectal cancer (CRC).

Methods

We determined the genotypes and alleles of MTHFR gene in 36 patients with histological confirmed CRC (19 women and 17 men) and in 36 normal controls matched for sex without a history of cancer. DNA was isolated from peripheral blood samples, and genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Results

In light of our results, the association of combined CT and TT genotypes and T allele was associated with an increased risk of CRC odds ratio 6.88 [95% confidence interval (CI): 2.30–20.49, P = 0.0005), 5.91 (95% CI: 2.14–16.34, P = 0.0006), and 2.96 (95% CI: 1.4–6.25, P = 0.0045), respectively. TT homozygous was not a protective factor in our study with an odds ratio of 2.36 (95% CI: 0.63–17.65, P = 0.16). Relative risk, individuals carrying at least one T allele have a 2-fold greater risk of developing CRC.

Conclusion

The MTHFR C677T gene variant was a risk factor for CRC in our population under study.

Résumé

Présentation

La méthylènetétrahydrofolate réductase (MTHFR) est une enzyme clé dans le métabolisme folique. Elle est impliquée dans la synthèse, la réparation et la méthylation de l’ADN. Le polymorphisme du gène MTHFR le plus souvent étudié est le C677T, qui est impliqué dans la pathogenèse de nombreuses maladies, dont le cancer. Cette étude, portant sur un groupe cas-témoins apparié, a été menée pour analyser l’association du polymorphisme MTHFR C677T et du risque de cancer colorectal.

Méthodes

Nous avons déterminé les génotypes et les allèles du gène MTHFR chez 36 patients présentant un cancer colorectal confirmé histologiquement (19 femmes et 17 hommes) et chez 36 témoins normaux appariés selon le sexe sans antécédents de cancer. L’ADN a été isolé à partir de sang périphériques et les génotypes ont été déterminés par PCR-RFLP.

Résultats

Nos résultats montrent que la combinaison de génotypes CT et TT et d’allèles T est associée à un risque accru de CRC de 6,88 (avec un intervalle de confiance [IC] de 95 %: 2,30–20,49, p = 0,0005), de 5,91 (IC 95 %: 2,14–16,34, p = 0,0006) et de 2,96 (IC 95 %: 1,4–6,25, p = 0,0045). Les homozygotes TT n’ont pas été un facteur de protection dans notre étude, avec un taux de 2,36 (IC 95 %: 0,63–17,65, p = 0,16). Concernant le risque relatif, une personne porteuse d’au moins un allèle T présente un risque deux fois plus élevé de développer un CRC.

Conclusion

La variante génétique MTHFR C677T constitue un facteur de risque de cancer colorectal dans la population que nous avons étudiée.

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Abbreviations

5-MTHF:

5-methyltetrahydrofolate

5,10-MTHF:

5,10-methylene tetrahydrofolate reductase

ADK:

adenocarcinoma

al :

collaborator

DNA:

deoxyribonucleic acid

dTMP:

deoxythymidylate monophosphate

dUMP:

deoxyuridylate monophosphate

CI:

confidence interval

CRC:

colorectal cancer

LGPM:

genetics and molecular pathology laboratory

Ml:

milliliter

MS:

methionine synthase

MTHFR:

methylene tetrahydrofolate reductase

OR:

odd ratio

PCR:

polymerase chain reaction

RFLP:

restriction fragment length polymorphism

RNA:

ribonucleic acid

RR:

relative risk

SAM:

S-adenosylmethionine

TNM:

tumor, node, metastasis

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Correspondence to S. Nadifi.

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Diakite, B., Benmoussa, A., Hamzi, K. et al. Colorectal cancer and polymorphism of methylenetetrahydrofolate reductase (C677T) in Morocco. J Afr Cancer 4, 238–244 (2012). https://doi.org/10.1007/s12558-012-0233-x

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  • DOI: https://doi.org/10.1007/s12558-012-0233-x

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