Phase I/II enzyme gene polymorphisms and esophageal cancer risk: a meta-analysis of the literature.
OBJECTIVE
Phase I/II enzymes metabolize environmental carcin-ogens and several functional polymorphisms have been reported in their encoding genes. Although their significance with regard to esophageal carcinogenicity has been examined epidemiologically, it remains controversial. The present systematic review of the literature was performed to clarify associations.


METHODS
Eligible studies were case-control or cohort studies published until September 2004 that were written in any language. From PubMed and a manual review of reference lists in relevant review articles, we obtained 16 studies related to the CYP1A1 Ile-Val substitution in exon 7, CYP1A1 MspI polymorphisms, CYP2E1 RsaI polymorphisms, GSTM1 null type, GSTT1 null type and GSTP1 Ile104Val. All were of case-control design. Summary statistics were odds ratios (ORs) comparing heterozygous-, homozygous-non-wild type or these two in combination with the homozygous wild type, or the null type with the non-null type for GSTM1 and GSTT1. A random effect model was used to estimate the summary ORs. A meta-regression analysis was applied to explore sources of heterogeneity.


RESULTS
Individuals with the Ile-Val substitution in CYP1A1 exon 7 had increased esophageal cancer risk, with ORs (95%CI) compared with Ile/Ile of 1.37 (1.09-1.71), 2.52 (1.62-3.91) and 1.44 (1.17-1.78) for Ile-Val, Val/Val genotype and the combined group. No significant association was found between esophageal cancer risk and the other genetic parameters.


CONCLUSIONS
A significant association exists between the CYP1A1 Ile-Val polymorphism and risk of esophageal cancer. Polymorphisms that increase the internal exposure to activated carcinogens may increase the risk of esophageal cancer.
Yang
Chun-Xia
CX
Department of Epidemiology, Huaxi Public Health School, Sichuan University, Chengdu 610041, Sichuan Province, China.
Matsuo
Keitaro
K
Wang
Zhi-Ming
ZM
Tajima
Kazuo
K
D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D004938:Esophageal Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D011110:Polymorphism, Genetic; D012307:Risk Factors
D007527:Isoenzymes; D019392:Cytochrome P-450 CYP2E1; D019363:Cytochrome P-450 CYP1A1; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase