Background: To find a genetic component in gastric cardia adenocarcinomas (GCA). Methods: Age at onset (AO) and rate of another synchronous primary upper gastrointestinal carcinoma (RASPUGIC) were compared among the three GCA groups with positive (N = 766), negative (N = 2167), and missing family history of upper gastrointestinal cancer (FHUGIC) (N = 198). These 3131 GCAs were diagnosed on 3128 primary GCA patients of a consecutive surgical cohort treated from 1973 through 1994 at the Department of Thoracic Surgery in the 4th Hospital of Hebei Medical University in a high-risk region in northern China. Results: Overall, GCAs of positive FHUGIC showed a significantly younger AO and a significantly higher RASPUGIC than the negative group (54.68 +/- 7.35 vs 55.94 +/- 7.47 years old, Pt-test = 0.000; 3.1% vs 1.3%, chi 2 = 11.02, P = 0.001). The difference in AO and RASPUGIC between the positive and the negative FHUGIC GCAs is significant or nearly significant in most subgroups; minimizing the possibility of a false association due to bias or confounding (e. g. significant stage-specific differences in AO between familial and sporadic GCAs observed in the subgroup of T2,3N0M0 (P = 0.000) and T2,3,4N1M0 (P = 0.03) exclude the possibility of ascertainment bias towards an earlier diagnosis in familial cases), and the association between FHUGIC and RASPUGIC is statistically significant for GCAs of younger AO (<55 yr old, RASPUGIC 3.8% vs 1.6% vs 1.1% for the positive, negative and missing FHUGIC GCAs respectively, chi 2 = 6.50, P = 0.04), but not significant for the later onset GCAs (>= 55 yr old, RASPUGIC 2.5%, 1.1%, 1.9% for the positive, negative and missing FHUGIC respectively, chi 2 = 4.22, P = 0.12). Conclusion: These findings suggest a genetic component in GCA in the Chinese high-risk region, and genetic predisposition may determine the age at onset and number of primary upper gastrointestinal cancer. (C) 2010 Elsevier Masson SAS. All rights reserved.