| The incidence of esophageal cancer has obvious regional distribution difference and some familial aggregation, indicating that environmental and genetic factors paly critical roles in the occurrence of esophageal cancer. Therefore, it is important to unravel the impacts of environmental factors and genetic factors on esophageal cancer, which will help us to assess the risk of individuals suffering from esophageal cancer, screen high-risk groups and targetedly take preventive measuares. In order to explain the genetic factors of esophageal cancer, we selected the mutation loci within mi R-196a2, mi R-499 and GSTs gene superfamily as target sites to explore their interactive association with esophageal cancer susceptibility. The results are listed as follows: 1. Associations between rs11614913, rs3746444 and esophageal squamous cell carcinoma riskThe two SNP sites, rs11614913 and rs3746444 within mi R-196a2 and mi R-499 separately have been studied to involve in carcinogenesis and development, but their relations with esophageal squamous cell carcinoma are still unknown. To shed some light on the relationship between rs11614913, rs3746444 and ESCC risk, we conducted this population-based case-control study.We totally recruited 3585 samples, including 1400 esophageal squamous cell carcinoma patients and 2185 cancer-free controls. mi R-196a2 rs11614913 and mi R-499 rs3746444 were genotyped using the SNa Pshot Multiplex System. Odds ratio(OR) and 95% confidence interval(95% CI) were used to assess the association between SNP and ESCC susceptibility. The CC genotype of mi R-196a2 rs11614913 was significantly associated with an increased ESCC risk compared with the TT genotype(OR(28)1.11, 95% CI(28)1.01-1.22) and the TT/TC genotypes(OR(28)1.09, 95% CI(28)1.01-1.19). The association was more significant in non-drinkers in the recessive model(OR(28)1.13, 95% CI(28)1.01-1.27). A significantly increased risk of ESCC associated with mi R-499 rs3746444 polymorphism was evident among patients who never smoking and drinking. In conclusion, this study suggests that mi R-196a2 rs11614913 and mi R-499 rs3746444 are associated with an increased ESCC risk in a Chinese population. 2. Meta-analysis of GSTs polymorphisms and esophageal cancer riskGlutathione S-transferases(GSTs) are important phase II enzymes and widely expressed in mammalian cytosols and membranes. GSTs are mainly responsible for eliminating electrophilic carcinogens through catalyzing the conjugation with glutathione. Glutathione S-transferase M1(GSTM1), T1(GSTT1) and P1(GSTP1) are the main types of GSTs, all of which have high expression level in esophageal mucosa. GSTM1 and GSTT1 mainly present the entire gene deletion variants, and GSTP1 presents an A313 G substitution(rs1695) resulting Ile105 Val. Numerous studies have examined the susceptibility to esophageal cancer conferred by these polymorphisms in GSTs. However, these results were inconclusive and inconsistent. To get a precise conclusion, we conducted a meta-analysis through collecting related articles. We finally recruited 42 published articles. GSTM1 null genotype and GSTT1 null genotype could significantly increase esophageal cancer risk(OR=1.38, 95% CI=1.23-1.55; OR=1.11, 95% CI=1.00-1.23 respectively). Subgroup analysis showed that the two polymorphisms most likely contribute to ESCC risk and their effect were pronounced among Asians. While GSTP1 Ile105 Val polymorphism showed no significant effect. |
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