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Carcinogenesis Advance Access originally published online on July 11, 2006
Carcinogenesis 2007 28(1):101-106; doi:10.1093/carcin/bgl124
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© The Author 2006. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

CYP2E1PstI/RsaI polymorphism and interaction with tobacco, alcohol and GSTs in gastric cancer susceptibility: a meta-analysis of the literature

Stefania Boccia1,*, Angelo De Lauretis1, Francesco Gianfagna1, Cornelia M.van Duijn2 and Gualtiero Ricciardi1

1 Institute of Hygiene, Catholic University of Sacred Heart, L.go F.Vito, 1-00168 Rome, Italy
2 Department of Epidemiology and Biostatistics, Erasmus Medical Center Rotterdam, The Netherlands

*To whom correspondence should be addressed. Tel: +0039 06 35001527; Fax: +0039 06 35001522; Email: sboccia{at}rm.unicatt.it

Studies investigating the association between cytochrome P450 2E1 (CYP2E1) 5'-flanking region (PstI/RsaI) polymorphism and gastric cancer risk report conflicting results. The rationale for this meta-analysis was to determine whether CYP2E1*2 (c2) variant allele of CYP2E1 increases gastric cancer risk, especially by interacting with smoking, alcohol and other metabolic gene polymorphisms. Two investigators independently searched the Medline and Embase databases. A qualitative scoring of papers was applied to their evaluation. Authors of the identified papers were contacted to obtain data on the mentioned co-exposures. A measurement of the biological interaction among two putative risk factors was estimated by the attributable proportion (AP) due to interaction. We identified 13 case–control studies, which included 2066 gastric cancer cases and 2754 controls. Using the random effects model, we found no association between PstI/RsaI genotype and gastric cancer risk [odds ratio (OR) = 0.97 (95% confidence interval (CI): 0.79–1.18) for c2 allele carriers and OR = 1.36 (95% CI: 0.82–2.25) for c2 homozygotes compared with homozygotes wild-type]. When only high-quality scored studies were considered, a statistically significant increased risk appeared among Asians [OR = 1.50 (95% CI: 1.16–1.94) for c2 carriers and OR = 2.62 (95% CI: 1.23–5.57) for c2 homozygotes]. No interaction was detected between CYP2E1-smoking/alcohol (AP = 0), while an AP of 60% appeared for individuals both c2 homozygotes and glutathione S-transferase M1 (GSTM1) null compared with both homozygotes wild-type. This meta-analysis suggests that the CYP2E1 PstI/RsaI polymorphism may be a risk factor for gastric cancer in Asians, and that a synergic relation among GSTM1 and CYP2E1 may account for a proportion of gastric cancer cases.


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