Study On The Relationgship Of Hla-drb1*0901 Gene, Hpv16e6 And Relatively Risk Factors With Kazakh's Esophageal Cancer In Xinjiang

Objective:1. To study the association between the environmental risk factors and genetic factors with esophageal cancer(EC) in Xinjiang Kazakh;2. To study the association between HLA-DRB1 * 0901 allele and HPV16E6 with esophageal cancer(EC) in Xinjiang Kazakh;3. To explore the role of the interaction between the HLA-DRB1 * 0901 allele with HPV16E6 in Kazakh's esophageal cancer(EC).Method:1. A 1:2 matched case-control study was conducted with 63 cases of EC and 126 controls. All the cases were collected from the six hospitals in north of Xinjiang during the periods from November 2006 to November 2008. Part of the controls were outpatients without history of malignant tumor, collected during the same period as cases; Another part of the controls were non-esophageal lesions selected from the census on gastrointestinal diseases among the normal population. The controls were matched by sex, nationality, area of residence and age within 5 years difference. To all the studies, the life behavioral factors epidemiological investigation were done and blood samples were collected. We gathered all the cases'paraffin-embedded tissues or fresh tumor tissues , and the controls'fresh esophageal mucosa.2. HLA-DRB1*0901 allele was identified from the blood samples by PCR; and HPV16E6 positive was identified from the paraffin-embedded tissues , fresh tumor tissues and fresh esophageal mucosa with PCR .3. All the calculations and statistics were performed with the computer program, SPSS Version 13.0. Statistical analysises adoptχ2 test, conditional logistic regression to calculate the values ofχ2, odds ratios and 95% confidence intervals for possible risk/protective factors.Result:1. Analysis the environmental risk factors and genetic factors,showed: excessive smoking,drinking wine and family history of EC were risk factors of EC in Kazakh.2. The frequencies of HLA-DRB1*0901 allele in Kazakh's EC and controls were 20.6 percent and 7.1 percent, respectively .The frequencies of EC group is different from the controls group (χ2=6.72,P=0.01). The individuals with HLA-DRB1*0901 allele had a 3.67-fold (95%CI:1.37～9.83) increased risk of developing EC in Kazakh.3. The frequencies of HPV16E6 positive in Kazakh's EC and controls were 36.5 percent and 16.7 percent, respectively .The frequencies of EC group is different from the controls group (χ2=7.90,P=0.005). The individuals with HPV16E6 positive had a 2.66-fold (95%CI: 1.34～5.25) increased risk of developing EC in Kazakh.4. Multivariate conditional Logistic regression analysis showed:HLA-DRB1*0901 allele and HPV16E6 were important risk factors of Kazakh's EC, the OR was 4.75(95%CI:1.10～20.59)and 2.79(95%CI:1.15～6.79), respectively;5. The gene-infection association analysis showed:In the case group, the frequencies of HPV16E6 positive was 69.2% and 28.0% in the HLA-DRB1*0901 allele positive group and negative group, respectively. In the controls group, the frequencies was 22.2% and 16.2%, respectively. Reactive effect analysis showed there was effect-modifications between the HLA-DRB1*0901 allele with HPV16E6 in Kazakh's esophageal cancer(EC).Conclusion:1. Unhealthy way of life such as excessive smoking, drinking wine and family history of EC were risk factors of EC in Kazakh of Xinjiang.2. Immune-related gene HLA-DRB1*0901 and biological-factor HPV16E6 could increase the chance of suffering from EC in Kazakh of Xinjiang.3. The HLA-DRB1*0901 allele and HPV16E6 may play a synergy in the course of the development of EC in Kazakh's.