CYP1A1 , CYP2E1 and EPHX1 polymorphisms in sporadic colorectal neoplasms

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.