A Match Case-control Study On Esophageal Cancer Susceptibility With Lifestyle Habits And Genetic Polymorphisms Of ALDH2 And ADH2

Objective: Along with the development of the ages, the mortality rate of esophageal cancer not only appears to descend the trend in the malignant tumor order in the whole world,but also has same situation in Sichuan Yanting County- (the high risk regions of esophageal cancer in China) . Our research work mainly to discover currently risk factors of esophageal cancer in Yanting and the distribute frequences of the genetype of ALDH2 and A0H2 in cases and controls.then to find the associations between the cancer and the genetic polymorphisms of ALDH2 and ADH2 ,at the same time ,to study the interaction between gene and lifestyle.Our study work went on under cooperation with the Yanting institute of treatment and prevention of tumour.Methods: One hundred and thirty-seven patients with EC (esophageal cancer) and one hundred and thirty-seven controls were enrolled in the study.The cases and controls were matched according by age and sex.The cases were confirmed by pathological diagnosis. All the cases and controls were investigated by self-designed questionnaires that contained items of general informations, esophageal cancer family history,lifestyles( smoking,drinking et al),dietary habits,nutrition and food informations.The informations about EC of cases.as cancer tissue types and site also been asked .About 5ml venous blood of each person was been collected for extracting genome DNA.so that to detect the genetyles of ADH2 and ALDH2 through PCR-CTPP(duplex PCR with confronting two-pair primers).The risk factors of EC were analysed by multiple factors conditions logistic regression mdei.paired signed ranks test and so on use software SPSS(version 11.5) to estimate the relationship of genetic polymorphisms and EC,so that make progress on the analysis of interaction of gene and circumstance (as alcohol drinking and smoking) or among genes.Results: The smoking (0R=5.92, 95% CI:2. 53-13.89),alcohol intake (0R=15.4, 95% CI: 8.28~28. 66), genetype of ALDH2 ( x2 = 11.352, P= 0.003 )and dietary habits(such as hot food, quickly eat, fruits and water) has been the risk factors of esophageal cancer (P 0.017) in Yanting. In the cases group the genetype ALDH2*1/*1,ALDH2*1/*2 and ALDH2*2/*2 were 46.7%,51.8%and 1.5% vs in control groups were 57.7%,35.0% and 7.3%, the proportion of genetype ADH2*1/*1,ADH2*1/*2 and ADH2*2/*2 in cases were 19.0%,39.4% and 41.7%, contrast in controls were 10.2%, 35.8% > 54.0%.The study has discovered the allele ADH2*1 was also a risk factor to esophageal cancer (0R= 1.615,95% Cl:1.127~2.257).The roles that gene (ALDH2.ADH2) and circumstance (drinking,smoking) acted in EC were not same important.the lifestyes maybe more important than ALDH2 and ADH2 though the frequences of genetype of ALDH2 was difference in cases and controls.Conclusins: In dietary as hot food, quickly eat and water (surface water) were the risk factors to esophageal cancer,but the fruits was protection factor to avoid with EC (OR=0.186, 95%CI:0.069-0.501 );the smoking and alcohol intake were high risk to EC ,and the same time ,the strong interaction between the smoking and drinking has been discovered (Wald = 17. 413, P=Q.000). The mutation allele gene ALDH2*2 was a risk factor for EC (x 2=3.291, P=0.043). The allele frequences of ALDH2*1 and ALDH2*2 were 75.18% and 24.82% in control group, the allele frequences of ADH2*1 and ADH2*2 were 28.10% and 71.90% in control group, their distribute of allele frequences of ADH2 and ALDH2 were all according to the law of Hardy— Weinberg genetic equilibrium (x 2^1.81, P>0.1). The one that carried mutated allele (especially carried ALDH2*2) has much risk for EC (OR=6.7, x 2=6.177, P=0.039) even he was lightdrinker. In all risk factors of EC, the circumstance played a more important roles than genetic factors.