Contribution of germline mutations in the BRCA and PALB2 genes to pancreatic cancer in Italy

• DOI: 10.1007/s10689-011-9483-5
• Publication Date: 2011-10-11T14:25:31Z
• Authors: P. Ghiorzo; V. Pensotti; G. Fornarini; S. Sciallero; L. Battistuzzi; F. Belli; L. Bonelli; G. Borgonovo; W. Bruno; A. Gozza; S. Gargiulo; L. Mastracci; S. Nasti; G. Palmieri; F. Papadia; L. Pastorino; A. Russo; V. Savarino; L. Varesco; L. Bernard; G. Bianchi Scarrà
• Keywords: Adult; Male; Breast Neoplasms; Adenocarcinoma; 03 medical and health sciences; 0302 clinical medicine; Humans; Genetic Predisposition to Disease; Germ-Line Mutation; Aged; Aged, 80 and over; BRCA2 Protein; Ovarian Neoplasms; BRCA; Germline mutation; Hereditary breast ovarian cancer syndrome (HBOC); PALB2; Pancreatic cancer susceptibility; Adenocarcinoma; Adult; Aged; Aged, 80 and over; BRCA1 Protein; BRCA2 Protein; Breast Neoplasms; Case-Control Studies; Fanconi Anemia Complementation Group N Protein; Female; Genetic Predisposition to Disease; Germ-Line Mutation; Humans; Italy; Male; Middle Aged; Nuclear Proteins; Ovarian Neoplasms; Pancreatic Neoplasms; Pedigree; Tumor Suppressor Proteins; Gene Deletion; Genetics; Oncology; Genetics (clinical); Cancer Research; BRCA1 Protein; Nuclear Proteins; Middle Aged; 3. Good health; Pancreatic Neoplasms; Italy; Case-Control Studies; Female; Fanconi Anemia Complementation Group N Protein; Pancreatic cancer susceptibility; BRCA; PALB2; Hereditary breast ovarian cancer syndrome (HBOC); Germline mutation; Gene Deletion

Pancreatic adenocarcinoma (PC) is the third most common cancer associated with BRCA mutations. Most notice has been given to BRCA2, while the association between BRCA1 and PC is less widely reported. Recently, PALB2 has been implicated in both PC and breast cancer (BC) susceptibility. We selected 29 Italian PC patients from a case-control study of PC according to their personal and family history of both PC and breast/ovarian cancer (BC/OC) and tested them for presence of germline mutations in BRCA1, BRCA2 and PALB2. We identified no germline mutations or deletions in PALB2, but detected 7 BRCA mutations (4 in BRCA1 and 3 in BRCA2). These findings suggest that PALB2 does not play a major role in PC susceptibility in our population. As we found an almost equal frequency of germline mutations in BRCA1 and BRCA2, germline alterations in either of these genes may explain a subset of Italian families presenting both PC and BC/OC. Moreover, as we began the observation of these families from probands who are affected by PC, we provide here a direct assessment of the role of PALB2 and BRCA mutations in PC susceptibility.