| Background:Cancers of the oral cavity, pharynx (other than nasopharynx), larynx and esophagus, collectively referred to as cancers of the upper aerodigestive tract (UADT), are among the most frequent cancers and the most common death causes of cancer in the world. Numerous evidences have well established alcohol drinking and tobacco smoking as the major environmental risk factors for UADT cancers. However, it is apparent that only a few fractions of drinkers and smokers develop UADT cancers ultimately. And abundant evidence also showed that UADT cancer risk affected by these factors is not uniform across genders and populations. In addition, some studies have also demonstrated that family-level factors play a part in the etiology of UADT cancers. All these suggest that genetic factors combined with environmental risk factors play a crucial role in the development of UADT cancers in the general population. Thus lots of studies have been focused on the genetic variations of alcohol metabolizing enzymes and the gene-environment interactions on the UADT cancer risk. In alcohol metabolism, ethanol is first metabolized into acetaldehyde, chiefly by ADH1B, and acetaldehyde is subsequently oxidized into harmless acetate, mainly catalyzed by ALDH2. And acetaldehyde has been classified as a Group 1 human carcinogen by the International Agency for Research on Cancer (IARC), is regarded as the most toxic alcohol metabolite in alcohol-associated carcinogenesis to human. Recently, A number of studies have reported that the genetic single nucleotide polymorphisms (SNPs) of alcohol-metabolizing enzymes are involved in the progress of UADT cancers, most of them are focused on the polymorphic site G47A (rs1229984) in the ADH1B gene, which has been identified at codon 47 in exon 3 located on chromosome 4q23, leading to an amino acid change from arginine (CGC) to histidine (CAC), resulting in enhanced activity of ethanol metabolism. About 40-fold maximum velocity has been observed in the high-activity AA genotype of ADH1B as compared to the low-activity GG genotype. Thus we conducted a meta-analysis based on published eligible studies, to investigate the gene-environment interactions in determining the susceptibility to UADT cancers in Asian populations with ADH1B G47A(rs 1229984) polymorphism.Objectives:This study aimed to investigate the association between Alcohol Dehydrogenase-1B (ADH1B) G47A (rs 1229984) polymorphism combined with environmental factors and the upper aerodigestive tract (UADT) cancer risk.Materials and Methods:Relevant studies were identified by a search in PubMed, Web of Science, Cochrane Library, Google Scholar and Chinese Biomedical Database. Odds ratios (OR) and 95% confidence intervals (CIs) were used to assess the strength of the association.Results:28 published case-control studies with 11,788 UADT cancer patients and 21,093 controls were included in this meta-analysis. The overall analysis showed significant interactions in Asians under three tested ADH1B G47A genetic models (GG vs. GA+AA:OR= 2.66; GG vs. AA:OR=2.99; GG vs. GA:OR=2.38).In stratified analysis based on ethnicity, Chinese, Japanese, Thai, and Korean populations with the GG genotype were associated with increased UADT cancer risk compared with Indian and Iranian populations, indicating ethnic differences in UADT cancer susceptibility. Some fairly obvious distinctions were found to exist between males and females, suggesting gender variation in UADT cancer risk. The combined effect of GG genotype with alcohol drinking showed significantly higher UADT cancer susceptibility. Smokers with the G allele had 5.59-fold increase in UADT cancer risk, when compared with non-smokers carrying the AA genotype.Conclusion:This meta-analysis implying that ADH1B G47A (rs1229984) polymorphism contributed to the susceptibility to UADT cancers in Asian populations. And our result also revealed the ADH1B G47A (rs1229984) polymorphism combined with gender variation and environmental factors on the UADT cancer risk. |
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