Genetics and Molecular Biology Research Unit (UPGEM), Department of Molecular Biology, São José do Rio Preto Medical School (FAMERP), UPGEM-Bloco U6, Avenida Brigadeiro Faria Lima, no. 5416, São José do Rio Preto, SP 15090-000, Brazil.
Mol Biol Rep. 2012 Feb;39(2):887-93. doi: 10.1007/s11033-011-0813-3. Epub 2011 Jun 1.
Alterations in folate metabolism may contribute to the process of carcinogenesis by influencing DNA methylation and genomic stability. Polymorphisms in genes encoding enzymes involved in this pathway may alter enzyme activity and consequently interfere in concentrations of homocysteine and S-adenosylmethionine that are important for DNA synthesis and cellular methylation reactions. The objectives were to investigate MTHFD1 G1958A, BHMT G742A, TC2 C776G and TC2 A67G polymorphisms involved in folate metabolism on head and neck cancer risk and the association between these polymorphisms with risk factors. Polymorphisms were investigated in 762 individuals (272 patients and 490 controls) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Real Time-PCR. Chi-square and Multiple logistic regression were used for the statistical analysis. Multiple logistic regression showed that tobacco and male gender were predictors for the disease (P < 0.05). Hardy-Weinberg equilibrium showed that the genotypic distributions were in equilibrium for both groups in all polymorphisms studied. The BHMT 742GA or AA genotypes associated with tobacco consumption (P = 0.016) increase the risk for head and neck squamous cell carcinoma (HNSCC). The present study suggests that BHMT 742GA polymorphism associated to tobacco modulate HNSCC risk. However, further investigation of gene-gene interactions in folate metabolism and studies in different populations are needed to investigate polymorphisms and HNSCC risk.
叶酸代谢的改变可能通过影响 DNA 甲基化和基因组稳定性而促进致癌过程。参与该途径的基因编码酶的多态性可能改变酶活性，从而干扰同型半胱氨酸和 S-腺苷甲硫氨酸的浓度，这些物质对 DNA 合成和细胞甲基化反应很重要。本研究的目的是探讨叶酸代谢中 MTHFD1 G1958A、BHMT G742A、TC2 C776G 和 TC2 A67G 多态性与头颈部癌症风险的关系，以及这些多态性与危险因素之间的关系。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）和实时 PCR 方法，对 762 名个体（272 名患者和 490 名对照者）进行了多态性研究。采用卡方检验和多因素 logistic 回归进行统计学分析。多因素 logistic 回归显示，吸烟和男性是疾病的预测因素（P < 0.05）。哈迪-温伯格平衡表明，在所有研究的多态性中，两组的基因型分布均处于平衡状态。BHMT 742GA 或 AA 基因型与吸烟有关（P = 0.016），增加了头颈部鳞状细胞癌（HNSCC）的风险。本研究提示，BHMT 742GA 多态性与吸烟共同作用可调节 HNSCC 风险。然而，需要进一步研究叶酸代谢中的基因-基因相互作用以及在不同人群中的研究，以探讨多态性与 HNSCC 风险的关系。
