Capaccio Pasquale, Ottaviani Francesco, Cuccarini Valeria, Cenzuales Salvatore, Cesana Bruno Mario, Pignataro Lorenzo
IV Clinica Otorinolaringoiatrica, Azienda Ospedaliera L Sacco, Milan, Italy.
J Laryngol Otol. 2005 May;119(5):371-6. doi: 10.1258/0022215053945831.
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.
叶酸代谢失调可能导致细胞异常增殖，并通过诱导DNA低甲基化而易于引发癌变。叶酸途径可能会因相关基因（如亚甲基四氢叶酸还原酶（MTHFR）基因）的多态性或饮酒而发生改变。我们调查了导致MTHFR酶活性降低的核苷酸C677T和A1298C处的MTHFR突变与65例口咽喉癌患者和100例对照者对口咽喉癌易感性之间的关系。我们从外周血白细胞中分离出DNA。在口咽喉癌病例中，C677T杂合基因型更为常见（p = 0.018），MTHFR 677T的等位基因频率更高（p = 0.019），且基因型677TT/1298AA更为常见（p = 0.001）。在具有突变型MTHFR纯合子或双杂合子的中度饮酒者中发现患癌风险更高（OR分别为21.2和9.1；p趋势 = 0.002），并且这种关联在不同癌症部位（声门、声门上、口咽）均存在。我们的研究结果支持这样的假设，即饮酒与MTHFR多态性的相互作用可能对口咽喉道癌变易感性有影响。
