Esophageal cancer genetic project

本项目的总体目标是了解遗传学在食管癌和胃癌的病因学和预防中的作用。五种不同但互补的方法已被用于识别食管癌易感基因。首先，进行了一项肿瘤/非肿瘤研究，在太原建立了由数百例食管癌和胃癌（贲门癌和体癌）样本（肿瘤、非肿瘤、静脉血、手指针刺血和颊细胞）组成的生物样本库，以鉴定食管癌和胃癌易感基因和这些癌症的潜在早期遗传标记。已经进行了微卫星标记的高密度全基因组扫描，以确定潜在的热点，并在其他肿瘤/非肿瘤样本中进一步测试这些热点和其他候选标记。还将检查癌前形态学病变。其次，从高风险（阳城县）和低风险（北京）地区的数百名健康个体中收集了DNA血样，以检查选定基因组标记的多态性的潜在人群差异。第三，对食管癌和胃癌（贲门癌和胃癌）病例进行了一项大型病例对照研究，并用于评估本项目其他组成部分中确定的候选标记物的多态性，并评估基因-环境相互作用。第四，正在进行一项家族研究，该研究将允许在有2例或2例以上食管癌或胃癌病例的家族中将候选标志物与癌症联系起来。最后，正在进行内窥镜研究，以获得从正常到早期浸润性食管癌的疾病形态谱的标本，以表征分子进展。 最近的研究强调了UGI癌症GWAS和GWAS后分析，家族研究中受试者的外显子组测序，UGI癌症肿瘤的分析以及UGI癌症微生物组的研究。

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.