Background: To demonstrate the effect of an inherited predisposition in familial Esophageal Squamous Cell Carcinoma (ESCC) as opposed to the sporadic cancer form.
Methods: Differences in age of onset, prevalence rates of double primary ESCC, and post-operative survival rates between ESCC cases with (N = 476) and without (N = 1226) a family history of upper gastrointestinal cancer (FHUGIC, defined as having one or more first- or second-degree relatives with cancer of the esophagus or gastric cardia) were analyzed.
Results: Overall, familial ESCC cases show a significantly earlier onset age (51.9 +/- 8.2 versus 53.4 +/- 8.0, P(t)(-test) = .000), a significantly higher prevalence rate of double primary ESCC (2.73% Versus 1.22%, adjusted with TNM: X(MH)(2) = 4.029, P = .045), and a worse prognosis than the sporadic cases (P(wald) = .049). In subgroup analyses, the familial cases showed earlier onset and poor survival at most subgroups as opposed to the sporadic cases, and the difference was greater in early-stage rather than in late-stage groups (P(t-test) for difference in onset age in T(is,1)N0M0, T(2,3)N0M0, and T(2,3,4)N1M0 were .002, .006, and .081 respectively; and P(wald) for difference in survival in T(is,1)N0M0, T(2,3)N0M0, and in T(2,3,4)N1M0 were .010, .180, and .520 respectively).
Conclusion: These findings suggest the existence of familial as opposed to the sporadic ESCC. By the theory of "two-hit" origin of cancer, these findings also suggest that the "first hit", a genetic predisposition, is inherited in familial ESCC.