eISSN: 1896-9151
ISSN: 1734-1922
Archives of Medical Science
Current issue Archive Manuscripts accepted About the journal Special issues Editorial board Abstracting and indexing Subscription Contact Instructions for authors
SCImago Journal & Country Rank
2/2019
vol. 15
 
Share:
Share:
more
 
 
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
View full text
Get citation
ENW
EndNote
BIB
JabRef, Mendeley
RIS
Papers, Reference Manager, RefWorks, Zotero
AMA
APA
Chicago
Harvard
MLA
Vancouver
 
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

references:
INCA (Instituto Nacional do Câncer Estimativa) (2016). Incidência de cãncer no Brasil. Accessed January 24, 2018. Available in: http://www1.inca.gov.br/estimativa/2018/estimativa-2018.pdf.
Kitahara CM, Linet MS, Freeman LEB, et al. Cigarette smoking, alcohol intake, and thyroid cancer risk: a pooled analysis of five prospective studies in the United States. Cancer Causes Control 2012; 23: 1615-24.
Stansifer KJ, Guynan JF, Wachal BM, Smith RB. Modifiable risk factors and thyroid cancer. Otolaryngol Head Neck Surg 2015; 152: 432-7.
Prasad VV, Wilkhoo H. Association of the functional polymorphism C677T in the methylenetetrahydrofolate reductase gene with colorectal, thyroid, breast, ovarian, and cervical cancers. Onkologie 2011; 34: 422-6.
Huang L, Zhang T, Xie C, et al. SLCO1B1 and SLC19A1 gene variants and irinotecan-induced rapid response and survival: a prospective multicenter pharmacogenetics study of metastatic colorectal cancer. PloS One 2013; 8: e77223.
Zhuo X, Song J, Li D, Wu Y, Zhou Q. MTHFR C677T polymorphism interaction with heavy alcohol consumption increases head and neck carcinoma risk. Sci Rep 2015; 5: 10671.
Rai V. Folate pathway gene MTHFR C677T polymorphism and risk of lung cancer in Asian populations. Asian Pac J Cancer Prev 2014; 15: 9259-64.
Yang YM, Zhang TT, Yuan L, Ren Y. The association between the C677T polymorphism in MTHFR gene and the risk of thyroid cancer: a meta-analysis. Eur Rev Med Pharmacol Sci 2014; 18: 2097-101.
Alshatwi AA. Breast cancer risk, dietary intake, and methylenetetrahydrofolate reductase (MTHFR) single nucleotide polymorphisms. Food Chem Toxicol 2010; 48: 1881-5.
Weiner AS, Boyarskikh UA, Voronina EN, et al. Polymorphisms in the folate-metabolizing genes MTR, MTRR, and CBS and breast cancer risk. Cancer Epidemiol 2012; 36: E95-100.
Hosseini M. Role of polymorphism of methyltetrahydrofolate homocysteine methyltransferase (MTR) A2756G and breast cancer risk. Pol J Pathol 2013; 64: 191-5.
Eklof V, Van Guelpen B, Hultdin J, Johansson I, Hallmans G, Palmqvist R. The reduced folate carrier (RFC1) 80G > A and folate hydrolase 1 (FOLH1) 1561C > T polymorphisms and the risk of colorectal cancer: a nested case-referent study. Scand J Clin Lab Invest 2008; 68: 393-401.
Galbiatti AL, Ruiz MT, Pinto DR, et al. A80G polymorphism of reduced folate carrier 1 (RFC1) gene and head and neck squamous cell carcinoma etiology in Brazilian population. Mol Biol Rep 2011; 38: 1071-8.
Yin G, Kono S, Toyomura K, et al. Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and colorectal cancer: the fukuoka colorectal cancer study. Cancer Sci 2004; 95: 908-13.
Jiang-Hua Q, De Chuang J, Zhen-Duo L, Shu-de C, Zhenzhen L. Association of methylenetetrahydrofolate reductase and methionine synthase polymorphisms with breast cancer risk and interaction with folate, vitamin B-6, and vitamin B-12 intakes. Tumour Biol 2014; 35: 1895-901.
Gallegos-Arreola MP, Figuera-Villanueva LE, Ramos-Silva A, et al. The association between the 844ins68 polymorphism in the CBS gene and breast cancer. Arch Med Sci 2014; 10: 1214-24.
Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16: 1215.
Ahrendt SA, Chow JT, Yang SC, et al. Alcohol consumption and cigarette smoking increase the frequency of p53 mutations in non-small cell lung cancer. Cancer Res 2000; 60: 3155-9.
Wittke-Thompson JK, Pluzhnikov A, Cox NJ. Rational inferences about departures from Hardy-Weinberg equilibrium. Am J Hum Genet 2005; 76: 967-86.
Carvalho Barbosa RdeC, Menezes DC, Freire TF, Sales DC, Alencar VH, Rabenhorst SH. Associations of polymorphisms of folate cycle enzymes and risk of breast cancer in a Brazilian population are age dependent. Mol Biol Rep 2012; 39: 4899-907.
Kweon SS, Shin MH, Kim HN, Kim SH, Kang HC. Polymorphisms of methylenetetrahydrofolate reductase and glutathione S-transferase are not associated with the risk of papillary thyroid cancer in Korean population. Mol Biol Rep 2014; 41: 3793-9.
Siraj AK, Ibrahim M, Al-Rasheed M, et al. Polymorphisms of selected xenobiotic genes contribute to the development of papillary thyroid cancer susceptibility in Middle Eastern population. BMC Med Genet 2008; 9: 61.
Ozdemir S, Silan F, Hasbek Z, et al. Increased T-allele frequency of 677 C > T polymorphism in the methylenetetrahydrofolate reductase gene in differentiated thyroid carcinoma. Genet Test Mol Biomarkers 2012; 16: 780-4.
Fard-Esfahani P, Fard-Esfahani A, Saidi P, Fayaz S, Mohabati R, Majdi M. An increased risk of differentiated thyroid carcinoma in Iran with the 677C > T homozygous polymorphism in the MTHFR Gene. Cancer Epidemiol 2011; 35: 56-8.
Zara-Lopes T, Gimenez-Martins APA, Nascimento-Filho CHV, et al. Role of MTHFR C677T and MTR A2756G polymorphisms in thyroid and breast cancer development. Gen Mol Res 2016; 15: doi: 10.4238/gmr.15028222.
Di JJ, Wang JT, Ding L, Wang ZM, Gao ES. A case-control study on the association of RFC-1 polymorphism and cervical cancer. Zhonghua Liu Xing Bing Xue Za Zhi 2009; 30: 189-91.
Wang L, Chen W, Wang J, et al. Reduced folate carrier gene G80A polymorphism is associated with an increased risk of gastroesophageal cancers in a Chinese population. Eur J Cancer 2006; 42: 3206-11.
De Jonge R, Tissing WJE, Hooijberg JH, et al. Polymorphisms in folate-related genes and risk of pediatric acute lymphoblastic leukemia. Blood 2009; 113: 2284-9.
Kotsopoulos J, Zhang WW, Zhang S, et al. Polymorphisms in folate metabolizing enzymes and transport proteins and the risk of breast cancer. Breast Cancer Res Treat 2008; 112: 585-93.
Zhou D, Mei Q, Luo H, Tang B, Yu P. The polymorphisms in methylenetetrahydrofolate reductase, methionine synthase, methionine synthase reductase, and the risk of colorectal cancer. Int J Biol Sci 2012; 8: 819-30.
Zhao Y, Chen Z, Ma Y, et al. Lack of association between methionine synthase A2756G polymorphism and digestive system cancer risk: evidence from 39327 subjects. PloS One 2013; 8: e61511.
Galbiatti AL, Ruiz MT, Biselli-Chicote PM, et al. 5-Methyl-tetrahydrofolate-homocysteine methyltransferase gene polymorphism (MTR) and risk of head and neck cancer. Braz J Med Biol Res 2010; 43: 445-50.
Yu K, Zhang J, Zhang J, et al. Methionine synthase A2756G polymorphism and cancer risk: a meta-analysis. Eur J Hum Genet 2010; 18: 370-8.
Galbiatti AL, Ruiz MT, Raposo LS, Maniglia JV, Pavarino-Bertelli EC, Goloni-Bertollo EM. The association between CBS 844ins68 polymorphism and head and neck squamous cell carcinoma risk – a case-control analysis. Arch Med Sci 2010; 6: 772-9.
Kabat GC, Kim MY, Wactawski-Wende J, Rohan TE. Smoking and alcohol consumption in relation to risk of thyroid cancer in postmenopausal women. Cancer Epidemiol 2012; 36: 335-40.
Ma J, Huang M, Wang L, Ye W, Tong Y, Wang H. Obesity and risk of thyroid cancer: evidence from a meta-analysis of 21 observational studies. Med Sci Monit 2015; 21: 283-91.
Cho YA, Kim J. Thyroid cancer risk and smoking status: a meta-analysis. Cancer Causes Control 2014; 25: 1187-95.
Rinaldi S, Lise M, Clavel-Chapelon F, et al. Body size and risk of differentiated thyroid carcinomas: findings from the EPIC study. Int J Cancer 2012; 131: E1004-14.
Kim HJ, Kim NK, Choi JH, et al. Associations between body mass index and clinico-pathological characteristics of papillary thyroid cancer. Clin Endocrinol 2013; 78: 134-40.
FEATURED PRODUCTS
Quick links
© 2019 Termedia Sp. z o.o. All rights reserved.
Developed by Bentus.
PayU - płatności internetowe