A positive family history of esophageal/gastric cardia cancer with gastric cardia adenocarcinoma is associated with a younger age at onset and more likely with another synchronous esophageal/gastric cardia cancer in a Chinese high-risk area

Abstract 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%, χ 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 ( χ 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, χ 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.