Early age of onset, multiple primary malignancies and poor prognosis are indicative of an inherited predisposition to esophageal squamous cell carcinoma in familial rather than sporadic disease — An update based on 14- to 23-year follow-up

Abstract

OBJECTIVE To demonstrate the effects of an inherited predisposition to familial esophageal squamous cell carcinoma (ESCC) through the comparison and analysis of the clinicopathologic di ff erences between familial and sporadic ESCC cases. METHODS Differences in age of onset, prevalence rates of double primary ESCC, and survival rates between familial ESCC ( n = 476) and sporadic ESCC cases ( n = 1226) were analyzed. RESULTS Overall, familial ESCC cases showed a signifi cantly younger age of onset (51.9 ± 8.2 vs. 53.4 ± 8.0, Pt-test = 0.00), a significantly higher prevalence rate for double ESCC (2.73 % vs. 1.22%, adjusted with TNM: χMH2 = 4.029, P = 0.045), and a lower survival rate than in sporadic cases (Pwald = 0.04). The familial cases showed both a younger age of onset and poorer survival in most subgroups, and the differences were more marked in early-stage rather than in the late-stage disease groups. CONCLUSION Theses fi ndings confirm the existence of familial as opposed to sporadic ESCC. By the theory of the “two-hit” origin of cancer, these fi ndings also suggest that the “ first hit”, a genetic predisposition, can affect the age of onset, number of primary carcinomas, and the prognosis for familial ESCC patients.