NCI is collaborating with the Shanxi Cancer Hospital and Institute in Taiyuan, Shanxi Province, on a project to understand the role of genetics in the etiology, prevention, and early detection of upper gastrointestinal tract cancers, including esophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma (GCA), and gastric non-cardia adenocarcinoma, all cancers with high incidence and mortality in this region of China. By combining gene discovery and validation approaches with population-based field studies, NCI investigators seek to discover and test major susceptibility genes, identify and test potential early detection markers, and examine associations between germ-line genetic variants and cancer risk. For this project, clinical studies and a large case-control study have been completed, while a family linkage study and endoscopy study are ongoing. Laboratory studies are ongoing to profile ESCC and gastric cancer tumors and to characterize DNA variation, allelic loss, copy number variation, and epigenetic changes; RNA and microRNA expression; and protein expression. A recently-completed genome-wide association study of ESCC and gastric cancer in Chinese subjects based primarily on the Shanxi project identified multiple SNPs at 10q23 (including nonsynonymous SNPs in the PLCE1 gene) that were strongly associated with increased risk for both ESCC and gastric cardia cancer.