| BackgroundEsophageal cancer (ESCC) is a common cancer in the world. China is one of the countries where the incidence and mortality rates of esophageal cancer are particularly high, and there are about 250,000 patients newly diagnosed with esophageal cancer each year in China, accounting for more than half of the world's cases (1). Especially in some parts of northern China, for example, in Linzhou city, a well-known high-risk area for esophageal cancer, the mortality rate exceeds the Chinese average rate by 10-fold and the rate among Caucasian Americans by 100-fold (2). Alcohol consumption is an important risk factor for ESCC (5-10).Alcohol dehydrogenase-1B (ADH1B) plays significant role in the metabolism of a wide spectrum of substrates including biologically important substances and carcinogen from drinking. The SNP rs 1229984 G to A change leads to the increased activity of ADH1B.MethodsThe case-control cohort of this study has been described elsewhere previously (23). Briefly, patients were consecutively recruited between July 1999 and July 2004 at the Chinese Academy of Medical Sciences Cancer Hospital (Beijing). All patients with histopathologically confirmed ESCC were enrolled, and there was no sex and age restriction. Controls were cancer-free individuals randomly selected from a community cancer screening program for early detection of cancer based on a physical examination. Controls had no individual history of cancer and were frequency matched to patients for sex and age. At recruitment, each participant was personally interviewed to obtain detailed information on demographic characteristics, lifetime history of cigarette use, and family history of cancer. This study was approved by the Institutional Review Board of the Chinese Academy of Medical Sciences Cancer Institute.This study examined the association between rs 1229984 and risk of esophageal squamous cell carcinoma (ESCC) in 1001 ESCC cases/1391 controls. Odds ratios (OR) and 95%confidence intervals (CIs) were estimated by logistic regression.ResultsThe frequency distributions of selected characteristics of the patients and controls are presented in Table 1. There were no significant differences between ESCC patients and controls in terms of age and sex distributions, suggesting that the frequency matching was adequate. However, significantly more smokers were presented among ESCC cases than among controls (63.1%versus 49.2%; P= 2.14×10-11). Smoker had an increased risk for developing ESCC (OR= 2.17,95%CI= 1.78-2.64). This result clearly indicate that smoking is a risk factor for the ESCC in our study population.We found that subjects carrying the rs 1229984 GG genotype had significantly increased risk of ESCC (adjusted OR,2.81; 95%CI,2.18-3.62; P=1.05×10-15) compared with the AA genotype.ConclusionsIn the present study, we investigated whether the genetic polymorphism rs 1229984 A/G of ADH1B was associated with risk of ESCC in a Chinese population. We observed a significant difference in the distributions of ADH1B rs 1229984 A/G alleles and genotypes frequencies among ESCC patients and controls. Subjects carrying rs 1229984 GG genotype was at an increased risk for developing ESCC compared with subjects carrying AA genotype. In present study, we found ADH1B GG homozygote encoding less-active form of ADH1B could significantly enhance risk of ESCC. This polymorphism may play its role in developing cancer by altering drinking behavior. Numerous studies have reported that ADH1B A allele frequency is higher in non-alcoholics than in alcoholics, subjects with ADH1B GG genotype encoding less-active enzyme drink more alcohol, and have higher risk of alcoholism (25-27).These results suggest that ADH1B rs 1229984 polymorphism is involved in susceptibility to developing ESCC.
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