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Association between methylenetetrahydrofolate reductase polymorphisms, alcohol intake and oropharyngolaryngeal carcinoma in northern Italy

Published online by Cambridge University Press:  08 March 2006

Pasquale Capaccio
Affiliation:
IV Clinica Otorinolaringoiatrica, Azienda Ospedaliera ’L Sacco’, Milan, Italy.
Francesco Ottaviani
Affiliation:
IV Clinica Otorinolaringoiatrica, Azienda Ospedaliera ’L Sacco’, Milan, Italy.
Valeria Cuccarini
Affiliation:
IV Clinica Otorinolaringoiatrica, Azienda Ospedaliera ’L Sacco’, Milan, Italy.
Salvatore Cenzuales
Affiliation:
Centro Trasfusionale, Azienda Ospedaliera ’L Sacco’, Milan, Italy.
Bruno Mario Cesana
Affiliation:
Laboratorio Epidemiologico, Ospedale Maggiore di Milano IRCCS, Milan, Italy.
Lorenzo Pignataro
Affiliation:
I Clinica Otorinolaringoiatrica, Ospedale Maggiore di Milano IRCCS, Milan, Italy.

Abstract

Folate metabolism dysregulation may lead to abnormal cell proliferation andpredispose to carcinogenesis by inducing DNA hypomethylation. Folate pathways may be modified by polymorphisms in relevant genes, such as that for methylenetetrahydrofolate reductase (MTHFR), or by alcohol consumption. We investigated the relationship between MTHFR mutations at nucleotides C677T and A1298C, which cause reduced MTHFR enzyme activity, and susceptibility to oropharyngolaryngeal carcinoma in 65 patients and 100 controls. We isolated DNA from peripheral bloodleukocytes. In oropharyngolaryngeal carcinoma cases the C677T heterozygous genotype was more frequent (p = 0.018), the allele frequency of MTHFR 677T was greater (p = 0.019) and the genotype 677TT/1298AA was more frequent (p = 0.001). A higher risk of carcinoma was found in the case of moderate drinkers with mutant MTHFR homozygosis or double heterozygosis (OR = 21.2 and OR = 9.1, respectively; p trend = 0.002), and the association wasmaintained for the different cancer sites (glottic, supraglottic, oropharyngeal). Our findings support the hypothesis that the interaction of alcohol intake and MTHFR polymorphisms might contribute to susceptibility to carcinogenesis of the oropharyngolaryngeal tract.

Type
Research Article
Copyright
© 2005 Royal Society of Medicine Press

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