ENTEROPANCREATIC MALIGNANCY ASSOCIATED WITH MULTIPLE ENDOCRINE NEOPLASIA TYPE-1 - RISK-FACTORS AND PATHOGENESIS

BACKGROUND. Enteropancreatic malignancy is an important cause of morbi dity and mortality associated with multiple endocrine neoplasia type 1 (MEN 1). However, the risk factors and mechanisms of the tumorigenesi s of this malignancy are poorly understood. METHODS. The authors condu cted a retrospective study of factors associated with the development of malignant enteropancreatic tumor in 69 patients with MEN 1 belongin g to a single family. RESULTS. Metastatic enteropancreatic tumor and g astrinoma were identified in 20% and 36% of patients, respectively. Co mpared with MEN 1 patients who did not have an immediate family histor y of enteropancreatic malignancy, MEN 1 patients with a first-degree r elative affected by enteropancreatic malignancy had an increased risk of developing disseminated tumor (odds ratio, 3.7; P < 0.05). Ln addit ion, hypergastrinemia and advanced age were both associated with a sig nificant increase in the risk of enteropancreatic malignancy. Elevated serum gylcoprotein alpha subunit levels were associated with enteroch romaffin-like cell hyperplasia, gastric carcinoid formation, and disse minated enteropancreatic tumor in hypergastrinemic patients (P < 0.05) . CONCLUSIONS. Disease modifier factors act in concert with the MEN 1 gene to modulate the development of enteropancreatic neoplasia. it is possible to identify MEN 1 patients at high risk for developing aggres sive enteropancreatic tumors. Heritable disease modifier factor(s) aff ecting enteropancreatic malignancy appear to reside at loci distinct f rom that of the MEN 1 gene. Cancer 1998;83:428-34. (C) 1998 American C ancer Society.