Esophageal cancer genetic project

这个项目的总体目标是了解遗传学在食道癌和胃癌的病因和预防中的作用。已使用五种不同但互补的方法来识别食道癌易感基因。首先，在太原市开展了肿瘤/非肿瘤研究，建立了由数百例食道癌和胃癌(贲门和体表)标本(肿瘤、非肿瘤、静脉血、指尖血和口腔细胞)组成的生物标本库，以确定食道癌和胃癌的易感基因和潜在的早期遗传标记。用微卫星标记进行了高密度全基因组扫描，以确定潜在的热点，在更多的肿瘤/非肿瘤样本中进一步测试这些热点和其他候选标记正在进行中。癌前形态损害也将被检查。其次，从高危地区(阳城县)和低危地区(北京)采集了数百名健康个体的血液样本进行DNA检测，以检查所选基因组标记多态性的潜在群体差异。第三，已经进行了一项大型病例对照研究，研究对象是食道癌和胃癌(包括贲门癌和体癌)，并正在用于评估在该项目的其他组成部分中确定的候选标记物的多态性，以及评估基因与环境的相互作用。第四，一项家庭研究正在进行中，该研究将允许有两个或更多食道癌或胃癌病例的家庭将候选标记与癌症联系起来。最后，正在进行一项内窥镜研究，从从正常到早期浸润性食道癌的各种疾病的形态谱中获取标本，以表征分子进展。最近的研究重点是UGI癌GWAs和GWA后分析，家系研究中受试者的外显子组测序，UGI癌肿瘤的概况，以及UGI癌的微生物组研究。

The overall goal of this project is to understand the role of genetics in the etiology and prevention of esophageal cancer and gastric cancer. Five different but complementary approaches have been used to identify esophageal cancer susceptibility genes. First, a tumor/nontumor study has been conducted in which a biological specimen bank consisting of samples (tumor, nontumor, venous blood, finger stick blood, and buccal cells) from several hundred cases of esophageal cancer and gastric cancer (both cardia and body) was developed in Taiyuan for the identification of esophageal cancer and gastric cancer susceptibility genes and potential early genetic markers of these cancers. High-density genome-wide scans with microsatellite markers have been conducted to identify potential hot spots, and further testing of these hot spots and other candidate markers in additional tumor/nontumor samples is in progress. Premalignant morphologic lesions will also be examined. Second, blood samples for DNA have been collected from several hundred healthy individuals from high-risk (Yangcheng County) and low-risk (Beijing) areas to examine potential population differences in polymorphisms for selected genomic markers. Third, a large case-control study with cases of esophageal cancer and gastric cancer (both cardia and body) has been conducted and is being used to evaluate polymorphisms in the candidate markers identified in other components of this project, and to evaluate gene-environment interactions. Fourth, a family study is in progress which will permit linkage of candidate markers with cancer in families having 2 or more cases with esophageal cancer or gastric cancer. Finally, an endoscopic study is being conducted to obtain specimens from a morphologic spectrum of disease ranging from normal to early invasive esophageal cancer in order to characterize molecular progression. Recent studies have emphasized UGI cancer GWAS and post-GWAS analyses, exome sequencing of subjects in the family study, profiling of UGI cancer tumors, and studies of the microbiome of UGI cancers.