Familial aggregation of malignant tumors in patients with pancreatic cancer: Findings from the Ragusa Cancer Registry (Sicily)

Abstract

Background and aims: Pancreatic cancer usually appears as a sporadic neoplasm, but there is increasing evidence that familialand hereditary factors may be involved in its pathogenesis. Using data from the population-based Ragusa Cancer Registry, weanalyzed trends in the incidence of pancreatic cancer, as well as the presence and type of familial aggregation of tumors inpancreatic cancer patients.

Methods: The incidence of pancreatic cancer in Ragusa Province was taken from the local cancer registry for 1981-2009, andtrends were analyzed. 142 of the 384 cases of pancreatic cancer diagnosed in 2000-2007 (37%, 84 men, 58 women) were usedfor analyses of familial aggregation. Pancreatic cancer patients or their relatives were traced, contacted, and interviewed. Theresultant information was used to compile a family history of disease, especially cancer, using our original pancreatic cancerpatients as probands. Based on these family histories of disease, probands were divided into four categories: sporadic, simplefamilial aggregation, aspecific verticality, and site-specific verticality. Analyses of familial aggregation and survival were thencarried out by presence (sporadic vs. familial cases) and type of familial aggregation (i.e., simple familial aggregation vs. aspecificand site-specific verticality).

Results: The incidence of pancreatic cancer increased gradually in 1981-2009 in both sexes. No familial aggregation wasobserved for 47 of the probands (sporadic cases), whereas the remaining 95 (67%) probands showed a more or less markedfamilial aggregation. Simple familial aggregation was observed in 43 of the probands, aspecific verticality in 49, and site-specificverticality in 3 probands. Cancer of the breast (43 cases, 16.5% of the total), central nervous system, stomach, and colon-rectumwere most frequently reported among relatives of probands. Survival analysis showed the usual poor prognosis of pancreaticcancer across all probands, regardless of presence or type of familial aggregation. Probands with familial aggregation did notdiffer from those with sporadic pancreatic cancer regarding stage of the disease, histological type, observed survival, or frequencyof multiple tumors.

Conclusions: Pancreatic cancer patients showed a striking familial aggregation of malignant tumors, especially for cancer ofthe breast. Our attempt to classify probands by presence and type of familial aggregation might contribute relevant clues tothe identification of inherited syndromes involving the pancreas. The marked association with breast cancer may suggest theinvolvement of BRCA1 and 2 gene mutations in the pathogenesis of some clusters of pancreatic cancer.