eISSN: 1896-9151
ISSN: 1734-1922
Archives of Medical Science
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SCImago Journal & Country Rank
2/2019
vol. 15
 
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abstract:
Basic research

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

Tairine Zara-Lopes
,
Ana Lívia Silva Galbiatti-Dias
,
Márcia Maria Urbanin Castanhole-Nunes
,
João Armando Padovani-Júnior
,
José Victor Maniglia
,
Erika Cristina Pavarino
,
Eny Maria Goloni-Bertollo

Arch Med Sci 2019; 15, 2: 522–530
Online publish date: 2019/02/05
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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 CßS 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 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, codominant 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 (χ2 = 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.

keywords:

genes, genetic polymorphism, thyroid cancer

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