Polymorphisms in MTHFR, MTR, RFC1 and C beta S genes involved in folate metabolism and thyroid cancer: a case-control study

Autor(es)

Zara-Lopes, Tairine ^[1] ; Silva Galbiatti-Dias, Ana Livia ^[1] ; Urbanin Castanhole-Nunes, Marcia M. ^[1] ; Padovani-Junior, Joao Armando ^[2] ; Maniglia, Jose Victor ^[2] ; Pavarino, Erika Cristina ^[1] ; Goloni-Bertollo, Eny Maria ^[1]

Afiliação do(s) autor(es)

^[1] Sao Jose do Rio Preto Med Sch FAMERP, Dept Mol Biol, Genet & Mol Biol Res Unit UPGEM, Ave Brigadeiro Faria Lima 5416, BR-15090000 Sao Paulo - Brazil

^[2] Sao Jose do Rio Preto Med Sch FAMERP, Otorhinolaryngol & Head & Neck Surg Dept, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Archives of Medical Science; v. 15, n. 2, p. 522-530, MAR 2019.
• Citações Web of Science: 0

Resumo

Introduction: 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 MTHFR 677C>T (rs1801133), MTR 2756A>G (rs1805087), RFC1 80A>G (rs1051266) and C beta S 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. Material and methods: 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 chi(2) and multiple logistic regression were utilized for statistical analysis. Results: The polymorphisms analysis revealed an association between the MTHFR 677C>T polymorphism (OR = 2.87, 95% CI: 1.50-5.48, p < 0.01, co-dominant model), (OR = 1.76, 95% CI: 1.18-2.64, p < 0.01, dominant model), (OR = 2.37, 95% CI: 1.28-4.39, p < 0.01, recessive model) and thyroid cancer. RFC1 80A>G polymorphism also was associated with thyroid cancer under recessive mode of inheritance (OR = 1.55; 95% CI: 1.02-2.38; p = 0.04); however, this polymorphism showed Hardy-Weinberg disequilibrium in the control group (chi(2) = 24.71, p < 0.001). Furthermore, alcohol (OR = 1.56, 95% CI: 1.36-1.89, p < 0.01) and tobacco consumption (OR = 1.97, 95% CI: 1.28-3.04, p < 0.01) were associated with increased risk for thyroid cancer. The MTR 2756A>G polymorphism showed an association with tumor extent (OR = 2.69, 95% CI: 1.27-5.71, p < 0.01) and aggressiveness (OR = 4.51, 95% CI: 1.67-12.1, p < 0.01). Conclusions: MTHFR 677C>T is significantly associated with increased risk for thyroid cancer and MTR 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. (AU)

• Processo FAPESP: 12/14781-1 - Avaliação dos polimorfismos de genes metabolizadores de xenobióticos (GSTM1, GSTT1, GSTP1 e mEH) em pacientes com cirrose e carcinoma hepatocelular
• Beneficiário: Eny Maria Goloni Bertollo
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 10/12930-4 - Avaliação de quimioterápicos, expressão gênica e quantificação de proteínas em carcinoma de cabeça e pescoço
• Beneficiário: Eny Maria Goloni Bertollo
• Modalidade de apoio: Auxílio à Pesquisa - Regular