The aim of this paper is to review and evaluate, in a comprehensive manner, the published data regarding the contribution of genetic polymorphisms to risk of esophageal cancer, including squamous cell carcinoma (SCC) and adenocarcinoma, in humans. All relevant studies available in MEDLINE and published before February 2007 were identified. Studies carried out in humans and that compared esophageal cancer patients with at least 1 standard control group were considered for analysis. One-hundred studies and 3 meta-analyses were identified. Eighty (80%) studies were conducted in Asian countries, particularly China including Taiwan (60 (60%) studies). The most intensively examined genes were those encoding carcinogen metabolic enzymes. The most widely studied gene was GSTM1 (15 studies), followed by ALDH2 (11 studies). ALDH2, MTHFR C677T, CYP1A1 Ile/Val, CYP1A1MspI, CYP2E1, GSTP1, GSTM1 and GSTT1 were examined by meta-analyses and significant relations were found between ALDH2*1*2 and the CYP1A1 Val allele and increased risk of esophageal cancer. In addition, increased risk of esophageal SCC was consistently associated with the ADH2*1*2 and the p53 codon 72 Pro/Pro genotypes. Cohort studies that simultaneously consider multiple genetic and environmental factors possibly involved in esophageal carcinogenesis are needed to ascertain not only the relative contribution of these factors to tumor development but also the contributions of their putative interactions.

Genetic polymorphisms and esophageal cancer risk

Glutathione-S-transferases M1 (GSTM1) and GSTT1 genotype, smoking, consumption of alcohol and tea and risk of esophageal and stomach cancers : a case-control study of a high-incidence area in Jiangsu Province, China

GSTT1, GSTM1 and GSTP1 genetic polymorphisms and interaction with tobacco, alcohol and occupational exposure in esophageal cancer patients from North India.

AIM: 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 refe-rence 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.

CONCLUSION: 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.

Phase I/II enzyme gene polymorphisms and esophageal cancer risk: A meta-analysis of the literature

The Kashmir Valley has an elevated incidence rate of esophageal cancer (EC). Several environmental and genetic factors have been suspected for development of EC. A case-control study was performed in 135 EC patients and 195 healthy controls to analyze association of polymorphisms in glutathione S-transferase (GST) mu (GSTM1), GST theta (GSTT1), GST pi (GSTP1), GSTM3, Cytochrome P450 (CYP)1A1, and CYP2E1 genes with susceptibility to EC as well as their interaction with environmental factors such as smoking and high consumption of salted tea in Kashmir valley. All subjects were genotyped through polymerase chain reaction restriction fragment length polymorphism. Data was statistically analyzed using the chi-square test and logistic regression model. Results showed that GSTP1313 val/val and CYP2E1c1c2 genotypes imparted risk for esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma [EADC; odds ratio (OR) = 3.24, 95% confidence interval (CI) = 1.30–8.05; OR = 4.20, 95% CI = 1.65–10.70], resp...

Association of Xenobiotic Metabolizing Enzymes Genetic Polymorphisms With Esophageal Cancer in Kashmir Valley and Influence of Environmental Factors

OBJECTIVE To investigate the association between susceptibility of esophageal squamous cell carcinoma and the genetic polymorphisms of CYP1A1 and GSTM1 METHODS Subjects were comprised of 107 esophageal cancer patients and 111 healthy controls Genotyping of both CYP1A1 and GSTM1 were performed in cancer tissues of all 107 patients and peripheral blood leukocytes taken from the controls by polymerase chain reaction RESULTS There were no significant differences in the frequency distribution of CYP1A1 polymorphisms between esophageal cancer patients and healthy controls although the frequency of CYP1A1 with at least one allele of Val showed slightly higher in individuals with esophageal cancer However, significant difference was observed in the frequency of GSTM1-nulled individuals with esophageal cancer comparing with the controls (P < 005) When subjects were categorized by both CYP1A1 genotype and GSTM1 genotype, GSTM1 (-) became markedly expressed in patients with CYP1A1 (I/I) than in the corresponding controls (67% versus 40%, P < 001) The frequency of CYP1A1 genotype with at least one allele of Val (I/V and V/V) was also statistically higher in patients with GSTM1 (+), comparing to the corresponding controls (64% versus 41%, P < 005) CONCLUSIONS It was suggested that: genetic polymorphisms of CYP1A1 and GSTM1 were susceptible to esophageal cancer; individuals who are GSTM1-null have an increased risk of developing esophageal cancer; individuals with combined CYP1A1 (I/I) and GSTM1 (-) or with combined CYP1A1 (I/V, V/V) and GSTM1 (+) were more susceptible, when comparing to those with combined CYP1A1 (I/I) and GSTM1 (+)

Su Y

Papers

[Relationship between CYP1A1, GSTM1 genetic polymorphisms and susceptibility to esophageal squamous cell carcinoma].