DNMT3B C46359T and SHMT1 C1420T polymorphisms in the folate pathway in carcinogenesis of head and neck
DNMT3B C46359T and SHMT1 C1420T polymorphisms in the folate pathway in carcinogenesis of head and neck
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DOI：
10.1007/s11033-013-2895-6
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发表时间：
2014-02-01
影响因子：
2.8
通讯作者：
Goloni-Bertollo, Eny Maria
中科院分区：
文献类型：
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作者：
Succi, Maysa;de Castro, Tialfi Bergamin;Goloni-Bertollo, Eny Maria
叶酸是一种必需的营养物质，在合成、修复和DNA甲基化过程中起着重要作用。参与叶酸代谢的编码酶基因的多态可以改变这些过程，并调节癌症的发展。我们研究了与叶酸途径相关的Dnmt3b C46359T(Rs2424913)和SHMT1 C1420T(Rs1979277)基因多态性与头颈癌(HNC)风险的关系，以及疾病与性别、危险因素和临床组织病理学参数的关系。对725名患者(237名HNC患者和488名对照)进行了病例对照研究。采用实时荧光定量聚合酶链式反应技术进行基因分型。统计分析采用卡方检验和多元Logistic回归分析。男性(OR1.8；95%CI1.11-2.94；P<；0.02)和烟草消费(OR6.14；95%CI4.13-9.13；P<；0.001)与肿瘤的风险增加相关。吸烟、饮酒习惯与SHMT1C1420T基因多态性相关(OR1.48；95%CI1.08~2.03；P=0.014)。SHMT1基因C1420T多态与喉部肿瘤相关(OR0.48；95%CI 0.27~0.86；P<；0.05)。综上所述，吸烟习惯和男性性别是HNC风险的预测因素。在巴西人群中，SHMT1 C1420T和Dnmt3b C46359T多态与HNC的发生无关，但SHMT1 C1420T多态在喉部原发肿瘤患者中的频率较低，而在同时吸烟和饮酒的患者中较高。进一步研究叶酸途径在不同人群中的基因-基因交互作用有助于了解基因多态对HNC风险的影响。
Folate is an essential nutrient with important roles in the synthesis, repair, and DNA methylation. Polymorphisms in genes encoding enzymes involved in folate metabolism can change these processes and modulate cancer development. We investigated DNMT3B C46359T (rs2424913) and SHMT1 C1420T (rs1979277) polymorphisms related to folate pathway in head and neck cancer (HNC) risk and the association of the disease with gender, risk factors and clinical histopathological parameters. A case-control study was conducted in 725 individuals (237 patients with HNC and 488 control individuals). Real-time PCR technique was performed for genotyping. Chi square and multiple logistic regression tests were used for statistical analysis. Male gender (OR 1.80; 95 % CI 1.11-2.94; P < 0.02) and tobacco consumption (OR 6.14; 95 % CI 4.13-9.13; P < 0.001) were associated with increased risk for this neoplasia. There were no significant associations between the polymorphisms and risk of disease, however, the tobacco and alcohol habits together showed association with SHMT1 C1420T polymorphism (OR 1.48; 95 % CI 1.08-2.03; P = 0.014). SHMT1 C1420T polymorphism was associated with larynx tumor (OR 0.48; 95 % CI 0.27-0.86; P < 0.05). In conclusion, tobacco habit and male gender can be predictors for HNC risk. SHMT1 C1420T and DNMT3B C46359T polymorphisms are not associated with HNC development in Brazilian population, however, SHMT1 C1420T polymorphism is less frequent in patients with primary site of tumor in larynx and more frequent in individuals who consume tobacco and alcohol together. Further studies involving gene-gene interactions in folate pathway in different populations can contribute to the understanding of the polymorphisms effect on HNC risk.