CYP1A1, CYP2E1 and EPHX1 polymorphisms in sporadic colorectal neoplasms

CYP1A1, CYP2E1 and EPHX1 polymorphisms in sporadic colorectal neoplasms

AIM To investigate the contribution of polymorphisms in the CYP1A1, CYP2E1 and EPHX1 genes on sporadic colorectal cancer(SCRC) risk. METHODS Six hundred forty-one individuals(227 patients with SCRC and 400 controls) were enrolled in the study. The variables analyzed were age, gender, tobacco and alc...

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Published in:World journal of gastroenterology : WJG Vol. 22; no. 45; pp. 9974 - 9983
Main Authors: Fernandes, Glaucia Maria M, Russo, Anelise, Proença, Marcela Alcântara, Gazola, Nathalia Fernanda, Rodrigues, Gabriela Helena, Biselli-Chicote, Patrícia Matos, Silva, Ana Elizabete, Netinho, João Gomes, Pavarino, Érika Cristina, Goloni-Bertollo, Eny Maria
Format: Journal Article
Language:English
Published: United States Baishideng Publishing Group Inc 07-12-2016
Subjects:
Age Factors
Brazil
Case Control Study
Case-Control Studies
Colorectal Neoplasms - genetics
Cytochrome P-450 CYP1A1 - genetics
Cytochrome P-450 CYP2E1 - genetics
Epoxide Hydrolases - genetics
Female
Humans
Logistic Models
Male
Middle Aged
Polymerase Chain Reaction
Polymorphism, Genetic
Polymorphism, Restriction Fragment Length
Polymorphism, Single Nucleotide
Real-Time Polymerase Chain Reaction
Risk Factors
Sex Factors
Single-nucleotide polymorphisms
Colorectal neoplasms
Cytochrome P-450 CYP1A1
Cytochrome P-450 CYP2E1
Epoxide hydrolases 1
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Summary:AIM To investigate the contribution of polymorphisms in the CYP1A1, CYP2E1 and EPHX1 genes on sporadic colorectal cancer(SCRC) risk. METHODS Six hundred forty-one individuals(227 patients with SCRC and 400 controls) were enrolled in the study. The variables analyzed were age, gender, tobacco and alcohol consumption, and clinical and histopathological tumor parameters. The CYP1A1 *2A, CYP1A1 *2C CYP2E1 *5B and CYP2E1 *6 polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). The EPHX1 Tyr113 His, EPHX1 His139 Arg and CYP1A1 *2C polymorphisms were detected by real-time PCR. Chisquared test and binary logistic regression were used in the statistical analysis. Haplotype analysis was conducted using the Haploview program, version 2.05.RESULTS Age over 6 2 years was a risk factor for SCRC development(OR = 7.54, 95%CI: 4.94-11.50, P < 0.01). Male individuals were less susceptible to SCRC(OR = 0.55, 95%CI: 0.35-0.85, P < 0.01). The CYP2E1*5B polymorphism was associated with SCRC in the codominant(heterozygous genotype: OR = 2.66, 95%CI: 1.64-4.32, P < 0.01), dominant(OR = 2.82, 95%CI: 1.74-4.55, P < 0.01), overdominant(OR = 2.58, 95%CI: 1.59-4.19, P < 0.01), and log-additive models(OR = 2.84, 95%CI: 1.78-4.52, P < 0.01). The CYP2E1*6 polymorphism was associated with an increased SCRC risk in codominant(heterozygous genotype: OR = 2.81, 95%CI: 1.84-4.28, P < 0.01; homozygous polymorphic : OR = 7. 3 2, 9 5 % C I : 1.85-28.96, P < 0.01), dominant(OR = 2.97, 95%CI: 1.97-4.50, P < 0.01), recessive(OR = 5.26, 95%CI: 1.35-20.50, P = 0.016), overdominant(OR = 2.64, 95%CI: 1.74-4.01, P < 0.01), and log-additive models(OR = 2.78, 95%CI: 1.91-4.06, P < 0.01). The haplotype formed by the minor alleles of the CYP2E1*5B(C) and CYP2E1*6(A) polymorphisms was associated with SCRC(P = 0.002). However, the CYP1A1 *2A, CYP1A1 *2C, EPHX1 Tyr113 His and EPHX1 His139 Arg polymorphisms were not associated with SCRC.CONCLUSION In conclusion, the results demonstrated that CYP2E1*5B and CYP2E1*6 minor alleles play a role in the development of SCRC.
Bibliography:Glaucia Maria M Fernandes;Anelise Russo;Marcela Alcantara Proen?a;Nathalia Fernanda Gazola;Gabriela Helena Rodrigues;Patrícia Matos Biselli-Chicote;Ana Elizabete Silva;Jo?o Gomes Netinho;érika Cristina Pavarino;Eny Maria Goloni-Bertollo;Genetics and Molecular Biology Research Unit-UPGEM, Department of Molecular Biology, S?o José do Rio Preto Medical School, FAMERP;Departament of Biology, UNESP-S?o Paulo State University;Departament of Surgery and Coloproctology Service, S?o José do Rio Preto Medical School, FAMERP
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Supported by São Paulo Research Foundation (FAPESP), No. 2011/23969-1 and No. 2012/02473-0; Coordination for the Improvement of Higher Education Personnel (CAPES) (Master grant) and National Council of Technological and Scientific Development (CNPq), No. 310582/2014-8.
Author contributions: Fernandes GMM planned and conducted the study, collected and interpreted data, drafted and wrote the manuscript; Biselli-Chicote PM performed the haplotype analysis and critically revised the manuscript; Netinho JG collected data on SCRC patients; Russo A participated in the collection of the genetic material, performed the analytical tools and revised the manuscript; Proença MA, Gazola NF and Rodrigues GH participated in the collection of the genetic material and performed the analytical tools; Silva AE and Pavarino ÉC served as scientific advisor; Goloni-Bertollo EM was the guarantor, planned the study and critically revised the manuscript.
Correspondence to: Eny Maria Goloni-Bertollo, PhD, Genetics and Molecular Biology Research Unit - UPGEM, Department of Molecular Biology, São José do Rio Preto Medical School, FAMERP, São José do Rio Preto, Av. Brigadeiro Faria Lima, 5416 Vila São Pedro, SP 15090-000, Brazil. eny.goloni@famerp.br
Telephone: +55-17-32015720 Fax: +55-17-32015708
ISSN:1007-9327
2219-2840
DOI:10.3748/wjg.v22.i45.9974