Zara-Lopes Tairine, Galbiatti-Dias Ana Lívia Silva, Castanhole-Nunes Márcia M Urbanin, Padovani-Júnior João Armando, Maniglia José Victor, Pavarino Erika Cristina, Goloni-Bertollo Eny Maria
Genetics and Molecular Biology Research Unit - UPGEM, Molecular Biology Department, São José do Rio Preto Medical School - FAMERP, São Paulo, Brazil.
Otorhinolaryngology and Head and Neck Surgery Department, São José do Rio Preto Medical School - FAMERP, São Paulo, Brazil.
Arch Med Sci. 2019 Mar;15(2):522-530. doi: 10.5114/aoms.2018.73091. Epub 2019 Feb 5.
Polymorphisms in genes coding enzymes involved in folate metabolism may cause alterations in this metabolic pathway and contribute to carcinogenesis, because folate is essential for DNA synthesis, methylation and repair. The objective of this study was to investigate the association of 677C>T (rs1801133), 2756A>G (rs1805087), 80A>G (rs1051266) and 844ins(68) (no rs#) polymorphisms and thyroid cancer development. The association of these polymorphisms with demographic risk factors and clinical histopathological parameters was also evaluated.
The study is a case-control analysis with a total of 462 individuals (151 patients and 311 controls). Polymerase chain reaction-restriction fragment length polymorphism technique was used for genotyping. The χ and multiple logistic regression were utilized for statistical analysis.
The polymorphisms analysis revealed an association between the 677C>T polymorphism (OR = 2.87, 95% CI: 1.50-5.48, < 0.01, codominant model), (OR = 1.76, 95% CI: 1.18-2.64, < 0.01, dominant model), (OR = 2.37, 95% CI: 1.28-4.39, < 0.01, recessive model) and thyroid cancer. 80A>G polymorphism also was associated with thyroid cancer under recessive mode of inheritance (OR = 1.55; 95% CI: 1.02-2.38; = 0.04); however, this polymorphism showed Hardy-Weinberg disequilibrium in the control group (χ = 24.71, < 0.001). Furthermore, alcohol (OR = 1.56, 95% CI: 1.36-1.89, < 0.01) and tobacco consumption (OR = 1.97, 95% CI: 1.28-3.04, < 0.01) were associated with increased risk for thyroid cancer. The 2756A>G polymorphism showed an association with tumor extent (OR = 2.69, 95% CI: 1.27-5.71, < 0.01) and aggressiveness (OR = 4.51, 95% CI: 1.67-12.1, < 0.01).
677C>T is significantly associated with increased risk for thyroid cancer and 2756A>G is associated with tumor extent and aggressiveness. In addition, alcohol and tobacco consumption were associated with increased risk of thyroid cancer. These results may contribute to a better prognosis for thyroid cancer.
编码参与叶酸代谢的酶的基因多态性可能导致该代谢途径发生改变，并促进癌症发生，因为叶酸对于DNA合成、甲基化和修复至关重要。本研究的目的是调查677C>T（rs1801133）、2756A>G（rs1805087）、80A>G（rs1051266）和844ins(68)（无rs编号）多态性与甲状腺癌发生之间的关联。还评估了这些多态性与人口统计学风险因素及临床组织病理学参数之间的关联。
本研究为病例对照分析，共纳入462名个体（151例患者和311名对照）。采用聚合酶链反应-限制性片段长度多态性技术进行基因分型。使用χ²检验和多因素逻辑回归进行统计分析。
多态性分析显示，677C>T多态性（共显性模型：OR = 2.87，95%CI：1.50 - 5.48，P < 0.01）、（显性模型：OR = 1.76，95%CI：1.18 - 2.64，P < 0.01）、（隐性模型：OR = 2.37，95%CI：1.28 - 4.39，P < 0.01）与甲状腺癌相关。80A>G多态性在隐性遗传模式下也与甲状腺癌相关（OR = 1.55；95%CI：1.02 - 2.38；P = 0.04）；然而，该多态性在对照组中显示出哈迪-温伯格不平衡（χ² = 24.71，P < 0.001）。此外，饮酒（OR = 1.56，95%CI：1.36 - 1.89，P < 0.01）和吸烟（OR = 1.97，95%CI：1.28 - 3.04，P < 0.01）与甲状腺癌风险增加相关。2756A>G多态性与肿瘤范围（OR = 2.69，95%CI：1.27 - 5.71，P < 0.01）和侵袭性（OR = 4.51，95%CI：1.67 - 12.1，P < 0.01）相关。
677C>T与甲状腺癌风险增加显著相关，2756A>G与肿瘤范围和侵袭性相关。此外，饮酒和吸烟与甲状腺癌风险增加相关。这些结果可能有助于改善甲状腺癌的预后。
