CYP1A1, CYP2E1 and EPHX1 polymorphisms in sporadic colorectal neoplasms

Author(s)

Fernandes, Glaucia Maria M. ; Russo, Anelise ; Proenca, Marcela Alcantara ; Gazola, Nathalia Fernanda ; Rodrigues, Gabriela Helena ; Biselli-Chicote, Patricia Matos ; Silva, Ana Elizabete ; Netinho, Joao Gomes ; Pavarino, Erika Cristina ; Goloni-Bertollo, Eny Maria

• Document type: Journal article
• Source: WORLD JOURNAL OF GASTROENTEROLOGY; v. 22, n. 45, p. 9974-9983, DEC 7 2016.
• Web of Science Citations: 3

Abstract

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 Tyr113His, EPHX1 His139Arg 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 62 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 = 7.32, 95% CI: 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 Tyr113His and EPHX1 His139Arg 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. (AU)

• FAPESP's process: 12/02473-0 - Epidemiological and molecular investigation of genes related to xenobiotic metabolism in patients with sporadic colerrectal cancer
• Grantee: Glaucia Maria de Mendonça Fernandes
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 11/23969-1 - Epidemiological and molecular investigation of genes related to xenobiotic metabolism in patients with sporadic colerrectal cancer
• Grantee: Eny Maria Goloni Bertollo
• Support Opportunities: Regular Research Grants