title: Association between methylenetetrahydrofolate reductase polymorphisms, alcohol intake and oropharyngolaryngeal carcinoma in northern Italy.
abstract: Folate metabolism dysregulation may lead to abnormal cell proliferation and predispose 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 blood leukocytes. 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 was maintained 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.
authors.affiliation: IV Clinica Otorinolaringoiatrica, Azienda Ospedaliera L Sacco, Milan, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Capaccio
authors.forename: Francesco
authors.initials: F
authors.lastname: Ottaviani
authors.forename: Valeria
authors.initials: V
authors.lastname: Cuccarini
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cenzuales
authors.forename: Bruno Mario
authors.initials: BM
authors.lastname: Cesana
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Pignataro
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007558:Italy; D007822:Laryngeal Neoplasms / Q000201:enzymology / Q000235:genetics*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000201:enzymology / Q000235:genetics*; D009154:Mutation; D010610:Pharyngeal Neoplasms / Q000201:enzymology / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2)