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CYP1A1,CYP2E1 and EPHX1 polymorphisms in sporadic colorectal neoplasms

World Journal of Gastroenterology 2016年第45期22卷 9974-9983页

作者： Glaucia Maria M Fernandes Anelise Russo Marcela Alcantara Proenca Nathalia Fernanda Gazola Gabriela Helena Rodrigues Patrícia Matos Biselli-Chicote Ana Elizabete Silva Joao Gomes Netinho érika Cristina Pavarino Eny Maria Goloni-Bertollo Genetics and Molecular Biology Research Unit-UPGEM Department of Molecular Biology Sao José do Rio Preto Medical School FAMERP Departament of Biology UNESP-Sao Paulo State University Departament of Surgery and Coloproctology Service Sao José do Rio Preto Medical School FAMERP

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 *** Age over 6 2 years was a risk factor for SCRC development(OR = 7.54, 95%CI: 4.94-11.50, P 1). Male individuals were less susceptible to SCRC(OR = 0.55, 95%CI: 0.35-0.85, P 1). The CYP2E1*5B polymorphism was associated with SCRC in the codominant(heterozygous genotype: OR = 2.66, 95%CI: 1.64-4.32, P 1), dominant(OR = 2.82, 95%CI: 1.74-4.55, P 1), overdominant(OR = 2.58, 95%CI: 1.59-4.19, P 1), and log-additive models(OR = 2.84, 95%CI: 1.78-4.52, P 1). 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 1; homozygous polymorphic : OR = 7. 3 2, 9 5 % C I : 1.85-28.96, P 1), dominant(OR = 2.97, 95%CI: 1.97-4.50, P 1), recessive(OR = 5.26, 95%CI: 1.35-20.50, P = 0.016), overdominant(OR = 2.64, 95%CI: 1.74-4.01, P 1), and log-additive models(OR = 2.78, 95%CI: 1.91-4.06, P 1). 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 *** In conclusion, the

关键词： Single-nucleotide polymorphisms Colorectal neoplasms Cytochrome P-450 CYP2E1 Cytochrome P-450 CYP1A1 epoxide hydrolases 1

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