Cytochrome P450 2E1 variable number tandem repeat polymorphisms and health risks: a genotype-phenotype study in cancers associated with drinking and/or smoking

Catanzaro,Irene; Naselli,Flores; Saverini,Marghereth; Giacalone,Antonio; Montalto,Giuseppe; Caradonna,Fabio

doi:10.3892/mmr.2012.914

Cytochrome P450 2E1 variable number tandem repeat polymorphisms and health risks: a genotype-phenotype study in cancers associated with drinking and/or smoking

Authors:
- Irene Catanzaro
- Flores Naselli
- Marghereth Saverini
- Antonio Giacalone
- Giuseppe Montalto
- Fabio Caradonna
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Affiliations: Department of Molecular and Biomolecular Sciences and Technologies (STEMBIO), Section of Cellular Biology, University of Palermo, I-90128 Palermo, Italy, Department of Internal and Specialist Medicine, University of Palermo, I-90100 Palermo, Italy
Published online on: May 14, 2012 https://doi.org/10.3892/mmr.2012.914
Pages: 416-420

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Abstract

Cytochrome P450 2E1 (CYP2E1) is one of the main enzymes involved in the oxidation of ethanol and in the transformation of a number of potentially dangerous compounds. It has various polymorphic sites, one of which is a variable number tandem repeat (VNTR) polymorphism previously described in the 5'-flanking region. The aim of this study was to investigate the genotype-phenotype association between CYP2E1 VNTR polymorphisms and risky health habits in healthy subjects and to analyze the associations between these polymorphisms with drinking- and/or smoking-related cancers. We analyzed 166 healthy subjects by genotyping for the CYP2E1 VNTR polymorphism associated with drinking and/or smoking habits by the more sensitive restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) method, using the NlaIV restriction enzyme. Sixty cases of pancreatic adenocarcinoma (PA) and 66 with hepatocellular carcinoma (HCC), were also genotyped. Statistical analysis was carried out to investigate the genotype-phenotype associations and to compare certain genotypes and cancer. We found 7 genotypes both in the healthy subjects and patients. The A1/A1 genotype was observed to be mainly associated with non-drinkers and -smokers (87.5 and 75.0%, respectively); moreover it was never found in the PA or HCC patients. Conversely, a weak association between A2/A3 with smokers (45.8%) and A4/A4 with drinkers (53.9%) was detected. In addition, the A4/A4 genotype was found to be significantly associated to PA [odds ratio (OR)=3.25; 95% confidence interval (CI) 1.21-7.50]. Our data demonstrate that certain CYP2E1 VNTR genotypes are associated with drinking and/or smoking habits; consequently, they may contribute either to the decreased or increased risk of developing drinking- and/or smoking-related cancers. In particular, we hypothesize that the A1/A1 VNTR genotype may have a protective role against drinking- and/or smoking-related cancers, and that A4/A4 may be a high-risk genotype during the early stages of cancer.

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