| Objective:To describe the epidemiology of the newly diagnosed cases of esophagus squamous carcinoma (ESCC) and explore the correlation between ESCC and alcohol drinking and other potential carcinogen.Methods:A case-control study was conducted with 283 newly diagnosed cases and 538 normal controls by questionnaires.Results:Average age, proportion of moderate drinkers, heavy drinkers and smokers in the ESCC cases were higher than the controls (P＜0.001). All types of alcohol consumption increase the risk of ESCC. The risk of ESCC increased gradually with light, moderate and heavy drinkers, OR=1.48,4.03,7.14. The risk of ESCC at the moderate and heavy beer drinkers increased, OR=4.19 and 8.83 (P=0.000). The risk of developing ESCC increased gradually with the light,moderate and heavy white spirit drinkers, OR=2.33,3.96,6.29 (P=0.007,0.000,0.000). The individuals who had drunk for more than 40 years were at the highest risk of ESCC, OR=6.31 (P=0.000). Compared with the drinkers who still drunk, the drinkers who had given up drinking for less than 5 years were at a higher risk of ESCC, OR=3.27 (P＜0.001). Conclusions:Alcohol drinking plays an important role in risk of ESCC. Alcohol drinking, especially drinking white spirit has harmful effect on developing ESCC, but drinking a little beer doesn't. Giving up drinking doesn't protect the body from developing ESCC. Keywords:esophageal carcinoma; epidemiologic study; alcohol drinking; danger factorObjective:The aim of this work was to detect expression of HO-1, HIF-1α, EGFR and VEGF165b in esophagus squamous carcinoma (ESCC) tissues, and then discuss their correlations with alcohol drinking and clinical pathological features in development of ESCC.Methods:Immunohistochemistry SP method was used to detect the expression of HO-1, HIF-1α, EGFR and VEGF165b in 143 ESCC tissues.Results:Positive expression rates of HO-1, HIF-1α, EGFR and VEGF165b in ESCC tissues were 40.6%,43.4%,58%and 13.3%respectively; Extend of drinking showed negative correlation with expression rate of HO-1 (P=0.001), and positive with expression rate of HIF-1αand EGFR. Expression rate of HO-1 was positive correlation with the histological grade (P=0.001), but no correlation with the clinical stage and mediastinal lymph node metastasis (P>0.05). Positive HIF-1αexpression was correlation with clinical stage,mediastinal lymph node metastasis and differentiation of tumor (P＜0.05). Positive expression of EGFR showed correlation with clinical stage and mediastinal lymph node metastasis (P＜0.05), but no correlation with the differentiation of tumor (P>0.05). The expression rate of VEGF165b showed no correlation with clinical stage,mediastinal lymph node metastasis and differentiation of tumor (P＞0.05). The expression rate of HO-1 showed positive correlation with the expression rates of HIF-1α,EGFR (P＜0.001), but no correlation with VEGF165b (P=0.206). HIF-1αexpression rate showed positive correlation with EGFR (P=0.040), and negative correlation with VEGF165b(P=0.035). There was no correlation between EGFR and VEGF165b (P=0.274).Conclusions:The expression of HO-1, HIF-1α, EGFR and VEGF165b play an important role in the occurrence and developement of ESCC. Alcohol drinking is a significant risk factor of ESCC and has great effort on the developing ESCC by influencing the expression of HO-1, HIF-1α, EGFR. The expression of HO-1 shows correlation with HIF-1αEGFR and VEGF165b.HO-1 and VEGF165b may be a potential therapy target.Objective:To evaluate correlation between alcohol drinking and expression of HO-1, and correlation between alcohol drinking and HO-1 gene promoter polymorphism along with risk of esophageal squamous cell carcinoma(ESCC) on Chinese males and study junction of (GT)n and T(-413)ASNP.Methods:Case-control study was performed in 143 ESCC patients and 264 cancer-free controls. Intracellular HO-1 expression in PBMCs was detected by flow cytometry. Genomic DNA was extracted from venous blood samples, HO-1(GT)n microsatellite polymorphism was examined by PCR-based genotyping and DNA sequencing. HO-1 T(-413)A SNP was detected by TaqMan probes method. Hardy-Weinberg equilibrium indicated an absence of discrepancies between genotype and allele frequencies. Linkage disequilibrium (LD) between these two polymorphisms was evaluated by linkage disequilibrium analysis program (LDA) and the haplotypes were built using PHASE2.0 program. The correlation between the polymorphism sites and haplotype with the risk of ESCC of the Chinese male alcohol drinkers were valued after adjusted and the functional correlation between the two polymorphisms was discussed with the expression of PBMCs HO-1.Results:(1) Compared with the controls, HO-1 expression in PBMCs in the ESCC was higher (56.8±12.05 MFI vs 35.4±22.70 MFI, P＜0.05).(2) Age, Frequency and consumption of alcohol drinking showed a significant difference between the cases and the controls. P＜0.001.(3) Distribution of the numbers of (GT)n repearts was bimodal, with two main peak located at 23 and 30 GT repeats. The cases carried a high L (55.6%vs 43.7%) and a low S (44.4% vs 56.3%) allele frequencies compared with the controls. The cases which carried a higher "S/L+L/L" (79.7%vs 65.9%) allele frequency were at a high risk of developing ESCC, OR=2.03 (95%CI 1.26-3.29, P=0.004), adjusted OR=2.21 (95%CI 1.30-3.78, P=0.004). After adjusting for age and smoking status, we estimated the risk for esophageal cancer in five drinking categories (never/rare, ex-drinkers, light, moderate, and heavy) by HO-1 (GT)n genotype. When subjects were analyzed according to alcohol consumption, the adjusted ORs for S/L and L/L compared with S/S were higher for heavy and moderate drinkers (in heavy drinkers, OR=3.24,95%CI 1.14-9.23, P=0.028; and in moderate drinker, OR=3.53,95%CI 1.28-9.73,P=0.015) than light/never/ex-drinkers (OR 1.11,95%CI 0.42-2.94, P=0.827/OR 1.15,95%CI 0.15-8.60,P=0.892/ORNC).(4) The T(-413)A SNP alleles and their distribution between cases and controls had no significant difference; The risk of developing ESCC between the T/A and A/A carriers and the T/T carriers had no significant difference after adjusted.(5) The D'value between HO-1(GT)n microsatellite polymorphism and T(-413)A SNP was 0.71, which showed a strong linkage. Compared with the ST haplotype, the LT haplotype was associated with the developing of ESCC after adjusted, OR=1.75 (95%CI 1.17-2.93, P=0.006).(6) The expression of PBMCs HO-1 in the cases and controls decreased with the increasing of the numbers of (GT)n-L allele after adjusted. The HO-1 expression in PBMCs of L/L carrier was the lowest. The HO-1 expression in PBMCs of the L/L carriers in the cases was manifestly lower than the S/S carriers(41.27±7.48 MFI vs 75.65±8.32 MFI), P=0.015. There was no significant difference between HO-1 expression in PBMCs in the cases and the T(-413)A SNP genotypes. The expression of PBMCs HO-1 of the T/T,T/A and A/A carriers in the cases and controls had no significant difference, P=0.557 and 0.538. The expression of PBMCs HO-1 of the L/L carriers in the light and moderate drinking groups was obviously lower than the S/S carriers, P=0.011 and 0.026, but it was not found in the heavy drinking groups.Conclusions:(1) The HO-1(GT)n microsatellite polymorphism is related to the developing ESCC of the Chinese male alcohol drinkers by regulating the expression of HO-1:the expression of HO-1 of L allele carriers is lower than S allele and has a higher risk of developing ESCC.(2). HO-1 expression in PBMCs with L(GT)n in heavy and moderate drinkers is obviously lower than with S(GT)n in light drinkers and non-drinkers, and the former may have a higher risk of developing ESCC.(3) There is a linkage between HO-1(GT)n microsatellite polymorphism and T(-413)A SNP; LT haplotype was associated with the developing of ESCC.(4) HO-1(GT)n microsatellite polymorphism may play an important role in regulating function of HO-1.(5) HO-1(GT)n microsatellite polymorphism serves as a novel genetic marker of ESCC, which could have guided significance for ESCC clinical prevention and treatment.
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