Predominant Ashkenazi BRCA1/2 mutations in families with pancreatic cancer.

The present study aimed to identify pancreatic cancer patients who harbor a mutation in BRCA1/2 genes within hereditary breast-ovarian cancer families. History of cancer in 1014 families that attended our breast-ovarian oncogenetic clinic was evaluated. Twenty-three families with pancreatic cancer were studied. In nine families wherein the probands themselves presented with pancreatic cancer, two (22%) carried a BRCA mutation (185delAG in BRCA1 in one case and 6174delT in BRCA2 in the other). In 14 families, only a family history of pancreatic cancer was elicited. Of these, seven families segregated either the 185delAG (three families) or the 6174delT (three families) mutation; one family segregated both mutations, but the parental status was not studied. Pedigree analysis shows that four of the seven pancreatic cancer cases were obligatory carriers. In summary, from among 23 families with pancreatic cancer, 6 (26%) informative BRCA1/2 mutation carriers were identified, equally cosegregating the 185delAG or the 6174delT mutation. Yet, it is not fully elucidated whether the risk for pancreatic cancer attributed to BRCA1 is similar to the high risk conferred by BRCA2. In Ashkenazi Jews, mutations in BRCA1/2 may constitute a major cause for pancreatic cancer.