| With ageing and the development of urbanization, the morbidity and mortality of chromic diseases is increasing steady. Chronic diseases account for an estimated80%of total deaths and70%of disability-adjusted life years (DALYs) lost in China. Cardiovascular diseases and cancer are the leading causes of both death and the burden of disease. The Taizhou Longitudinal Study (TZL) initiated by Fudan University, Peking University, Taizhou goverment and many other scientific research institutions in Taizhou aims to explore the environmental and genetic risk factors for chronic diseases. The TZL study is focused on exploring the multiple environmental and lifestyles exposures altered during the process of economic transformation of China, solely or in combination with multiple genetic factors, on the gradually increased prevalence of chronic diseases.Based on the TZL study, and also integrated the resources of several hospitals, we conducted the present study (part Ⅰ:Research on Environmental Factors in Etiology of Esophageal Cancer and part Ⅱ:Genetic Susceptibility Research on Atherosclerosis-related Phenotyps). Our goal was to assess the Molecular Epidemilogic features of chronic diseases such as esophageal cancer and atherosclerosis-related phnotypes in Chinese population.In part Ⅰ, we analysed the morbidity of Taixing from2003to2010and found that the crude incidence of esophageal cancer war60.67/100,000, the cumulative incidence of0～74was4.62%. There were5810cases during eight years and men accounted for most of the cases. Also the age of onset was older in men than in women. The absolute number of esophageal cancer cases was almost the same every year. We also found that the incidence of esophageal cancer showed steady trend in male and both gender, but significant decline by3.07%per year in female. We also found some behavioral patterns could increase the risk of esophageal cancer. Drinking might be the independent risk factor of esophageal cancer with an OR of2.21(1.42～2.43) and the risk increased with higher drinking frequency or longer drinking duration. By drinking tap water more than five years, the risk might decrease with an OR of0.56(0.35～0.88). food preservation without freezer or airtight container could increase the risk of esophageal cancer with OR of2.33(1.72～3.14) and2.99(2.10～4.25), respectively. Low frequency of brushing teeth (<1time per day) was associated with increased risk of esophageal cancer with an OR of2.02(1.56～2.62). To characterize the human oral microbial structure under various disease conditions such as ESCC, and understand the potential correlation of oral microbial variation and ESCC, we used barcoded454pyrosequencing method to characterize the oral microbiomes of human saliva samples from100newly diagnosed ESCC patients. Totally451,187high-quality16S rRNA gene V3/V4region sequences were obtained from all the samples. At phylum level, there were12bacterial phyla in the Chinese human oral cavity, dominated by Bacteroidetes, Firmicutes and Proteobacteria which account for almost90%of total oral bacteria. The diversity compostion of oral microbiome at phylum level exhibited remarkable sub-group deifference according to the βdiversity analysis. However, the specific global structure of oral microbiome seemed not to be related with sex or age, indicating that there would be some unknown factors which strongly influence oral microbiome. In summary, we conducted an population-based case control study with strict design, to explore the enviromental risk factors of esophageal cancer, and identified some risk factors such as drinking, oral health associated with ESCC.In part II, a two-stage genetic association study was conducted in Chinese Hans. Stage I included a cohort with451IS cases and462controls for association study using92SNPs. Stage II examined the associations of8positive variants and5additional variants with IS, MI, and ASCVD for validation in a cohort with779IS cases and836controls and a cohort with824MI cases and737controls. The T allele of rs4731702located near KLF14gene was associated with decreased risk of MI with an OR of0.72(p<3.85×10-3). The rs4731702-T allele was also associated with decreased risk of ASCVD with an OR of0.78(pcombined<5.43×10-4). In addition, we found that a missense variant of KLF14, rs111400400(Ser58Pro), was associated with MI. Then, we investigated the associations of SNPs of KCNQ1with metabolic phenotypes in a Uyghur population (n=478) and replicated these associations in a Han population (n=2,485). We found that rs2237892-T allele was significantly associated with decreased triglyceride levels (pcombined=0.001). The minor G allele of the rs12720449, with sharp difference of the allelic frequency between European and East Asian populations (0.2%versus14%, respectively), was associated with a lower triglyceride levels than G allele in Uyghur subjects (p=0.004), in Han subjects (p=0.052), and in subjects of meta-analysis (pcombined=0.001). Moreover, the minor A allele of the rs1057128was also associated with decreased triglyceride levels in meta-analysis (pcombined=0.010). In all, genetic variants near/in KLF14gene were newly identified to be implicated in the etiology of atherosclerotic related phenotypes, and rs12720449, a missense mutation of KCNQ1, was reported to be associated with triglyceride levels for the first time.The TZL study has becoming a very useful platform in Etiology studies of chronic diseases. Although we can not de longitudinal analysis based on current data, we can do cross-section studies and high-quality case-control studies on the platform. In present study, we used the the latest molecular biology technology and analysis methods to explore the molecular epidemiology features of esophageal cancer and atherosclerosis-ralated phnotypes, and wish our result can provide clues to other researchers. |
PDF Full Text Request