Carcinogenesis Advance Access published online on July 11, 2006
Carcinogenesis, doi:10.1093/carcin/bgl124
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1 Institute of Hygiene, Catholic University of Sacred Heart, Rome, Italy
* To whom correspondence should be addressed. 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 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 thirteen 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 [OR = 0.97 (95% 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 synergistic interaction among GSTM1 and CYP2E1 may account for a proportion of gastric cancer cases.
Received May 31, 2006
Accepted July 7, 2006
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
CYP2E1PstI/RsaI polymorphism and interaction with tobacco, alcohol and GSTs in gastric cancer susceptibility: a meta-analysis of the literature
Stefania Boccia 1 *,
Angelo De Lauretis 1,
Francesco Gianfagna 1,
Cornelia M. van Duijn 2,
and
Gualtiero Ricciardi 1
2 Department of Epidemiology & Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands
Stefania Boccia, E-mail: sboccia{at}rm.unicatt.it
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