Genetic Heterogeneity of Oesophageal Cancer in High-Incidence Areas of Southern and Northern China

Background and Objective: Oesophageal cancer is one of the most common and deadliest cancers worldwide. Our previous population-based study reported a high prevalence of oesophageal cancer in Chaoshan, Guangdong Province, China. Ancestors of the Chaoshan population migrated from the Taihang Mountain region of north-central China, which is another high-incidence area for oesophageal cancer. The purpose of the present study was to obtain evidence of inherited susceptibility to oesophageal cancer in the Chaoshan population, with reference to the Taihang Mountain population, with the eventual goal of molecular identification of the disease genes. Methods: We conducted familial correlation, commingling, and complex segregation analyses of 224 families from the Chaoshan population and 403 families from the Taihang population using the FPMM program of S. A. G. E. version 5.3.0. A second analysis focused on specific families having large numbers of affected individuals or early onset of the disease. Results: For the general population, moderate sib-sib correlation was noticed for esophageal cancer. Additionally, brother-brother correlation was even higher. Commingling analyses indicated that a three-component distribution model best accounts for the variation in age of onset of oesophageal cancer, and that a multifactorial model provides the best fit to the general population data. An autosomal dominant mode and a dominant or recessive major gene with polygenic inheritance were found to be the best models of inherited susceptibility to oesophageal cancer in some large families. Conclusions: The current results provide evidence for inherited susceptibility to oesophageal cancer in certain high-risk groups in China, and support efforts to identify the susceptibility genes.