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©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
Polymorphisms of folate metabolism genes in patients with cirrhosis and hepatocellular carcinoma
Nathália Perpétua Peres, Ana Lívia Silva Galbiatti-Dias, Márcia Maria Urbanin Castanhole-Nunes, Renato Ferreira da Silva, Érika Cristina Pavarino, Eny Maria Goloni-Bertollo, Mariangela Torreglosa Ruiz-Cintra
Nathália Perpétua Peres, Ana Lívia Silva Galbiatti-Dias, Márcia Maria Urbanin Castanhole-Nunes, Eny Maria Goloni-Bertollo, Mariangela Torreglosa Ruiz-Cintra, Érika Cristina Pavarino, Genetics and Molecular Biology Research Unit, UPGEM, São José do Rio Preto 15090-000, Brazil
Nathália Perpétua Peres, Ana Lívia Silva Galbiatti-Dias, Márcia Maria Urbanin Castanhole-Nunes, Renato Ferreira da Silva, Eny Maria Goloni-Bertollo, Érika Cristina Pavarino, São José do Rio Preto Medical School, FAMERP and Medical School Fundation, FUNFARME, São José do Rio Preto 15090-000, Brazil
Renato Ferreira da Silva, Mariangela Torreglosa Ruiz-Cintra, Study Group of Liver Tumors, GETF, Hospital de Base, São José do Rio Preto 15090-000, Brazil
Mariangela Torreglosa Ruiz-Cintra, Federal University of the Triângulo Mineiro, UFTM, Uberaba 38064-200, Brazil
Author contributions: All the authors contribute to the manuscript.
Institutional review board statement: The research project CAAE 20465713.1.0000.5415 under the responsibility of Mariangela Ruiz Torreglosa Cintra titled “Polymorphisms of folate metabolism genes in patients with cirrhosis and hepatocellular carcinoma” is in accordance with the resolution of the CNS 466/12 and was approved by that Ethics Research Committee.
Informed consent statement: Approved by that Ethics Research Committee.
Conflict-of-interest statement: The authors declare no conflicts of interest regarding this manuscript.
Data sharing statement: Patient data and full dataset are available with open accessfrom the corresponding author at analiviagalbiattidias@gmail.com. All Participants gave informed consent for data sharing. For more questions, please contact eny.goloni@famerp.br.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Eny Maria Goloni-Bertollo, MD, São José do Rio Preto Medical School, FAMERP and Medical School Fundation, FUNFARME, Av. Brigadeiro Faria Lima, 5416, São José do Rio Preto 15090-000, Brazil.
eny.goloni@famerp.br
Telephone: +55-17-32015720
Received: May 13, 2016
Peer-review started: May 16, 2016
First decision: June 14, 2016
Revised: June 22, 2016
Accepted: August 15, 2016
Article in press: August 16, 2016
Published online: October 18, 2016
Processing time: 154 Days and 16.2 Hours
AIM
To evaluated the association of the risk factors and polymorphisms in MTHFR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G genes.
METHODS
Patients with cirrhosis (n = 116), hepatocellular carcinoma (HCC) (n = 71) and controls (n = 356) were included. Polymerase chain reaction followed by enzymatic digestion and allelic discrimination technique real-time PCR techniques were used for analysis. MINITAB-14.0 and SNPstats were utilized for statistical analysis.
RESULTS
Showed that age ≥ 46 years (OR = 10.31; 95%CI: 5.66-18.76; P < 0.001) and smoking (OR = 0.47; 95%CI: 0.28-0.78; P = 0.003) were associated with cirrhosis. Age ≥ 46 years (OR = 16.36; 95%CI: 6.68-40.05; P < 0.001) and alcohol habit (OR = 2.01; 95%CI: 1.03-3.89; P = 0.039) were associated with HCC. MTHFR A1298C in codominant model (OR = 3.37; 95%CI: 1.52-7.50; P = 0.014), recessive model (OR = 3.04; 95%CI: 1.43-6.47; P = 0.0051) and additive model (OR = 1.71; 95%CI: 1.16-2.52; P = 0.0072) was associated with HCC, as well as MTR A2756G in the additive model (OR = 1.68; 95%CI: 1.01-2.77; P = 0.047), and MTRR A66G in the codominant model (OR = 3.26; 95%CI: 1.54-6.87; P < 0.001), dominant model (OR = 2.55; 95%CI: 1.24-5.25; P = 0.007) and overdominant model (OR = 3.05; 95%CI: 1.66-5.62; P < 0.001). MTR A2756G in the additive model (OR = 1.54; 95%CI: 1.02-2.33; P = 0.042) and smokers who presented at least one polymorphic allele for MTRR A66G (OR = 1.71; 95%CI: 0.77-3.82; P = 0.0051) showed increased risk for cirrhosis. There was no association between clinical parameters and polymorphisms.
CONCLUSION
Age ≥ 46 years, alcohol habit and MTR A2756G, MTHFR A1298C and MTRR A66G polymorphisms are associated with an increased risk of HCC development; age ≥ 46 years, tobacco habit and the MTR A2756G polymorphism are associated with cirrhosis.
Core tip: Our study is relevant because we can get better understanding on the mechanisms involved in the development of hepatocellular and Cirrhosis Carcinoma and folate metabolism. It is already known that polymorphisms cause DNA hypomethylation, which cause abnormal changes in gene expression inactivating suppressor genes tumor. In this study we have found some positive associations which was possible to understand the carcinogenesis of this tumor and offer new possibilities for diagnosis. Throughout these results it is possible to achieve better quality of life in early treatments.
