Genetic polymorphisms and esophageal cancer risk.
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.
Health Service Center, Hiroshima University, Higashihiroshima, Japan. tohiyama@hiroshima-u.ac.jp
Toru
T
Hiyama
Masaharu
M
Yoshihara
Shinji
S
Tanaka
Kazuaki
K
Chayama
D000230:Adenocarcinoma / Q000235:genetics*; D000429:Alcohol Oxidoreductases / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004260:DNA Repair; D004938:Esophageal Neoplasms / Q000235:genetics*; D005492:Folic Acid / Q000378:metabolism; D018816:Genes, cdc; D020022:Genetic Predisposition to Disease; D006801:Humans; D015201:Meta-Analysis as Topic; D016017:Odds Ratio; D009857:Oncogenes; D011110:Polymorphism, Genetic; D012307:Risk Factors
D003577:Cytochrome P-450 Enzyme System; D005492:Folic Acid; D000429:Alcohol Oxidoreductases