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CDKN2A is the main susceptibility gene in Italian pancreatic cancer families
  1. Paola Ghiorzo1,
  2. Giuseppe Fornarini2,
  3. Stefania Sciallero2,
  4. Linda Battistuzzi3,
  5. Fiorenza Belli4,
  6. Loris Bernard5,
  7. Luigina Bonelli6,
  8. Giacomo Borgonovo7,
  9. William Bruno1,
  10. Franco De Cian7,
  11. Andrea DeCensi8,
  12. Marco Filauro4,
  13. Francesca Faravelli9,
  14. Alberto Gozza8,
  15. Sara Gargiulo1,
  16. Frederique Mariette10,
  17. Sabina Nasti1,
  18. Lorenza Pastorino1,
  19. Paola Queirolo11,
  20. Vincenzo Savarino1,
  21. Liliana Varesco12,
  22. Giovanna Bianchi Scarrà1,13,
  23. the Genoa Pancreatic Cancer Study Group
  1. 1Department of Internal Medicine and Medical Specialties (DiMI), University of Genoa, Italy
  2. 2Medical Oncology Unit, San Martino-IST Research Hospital, Genoa, Italy
  3. 3Department of Health Sciences, University of Genoa, Genoa, Italy
  4. 4General and Biliopancreatic Surgery Unit, Galliera Hospital, Genoa, Italy
  5. 5FIRC Institute of Molecular Oncology Foundation, Milan, Italy
  6. 6Secondary Prevention and Screening, San Martino-IST Research Hospital, Genoa, Italy
  7. 7Department of Surgery, University of Genoa, Genoa, Italy
  8. 8Medical Oncology Unit, Galliera Hospital, Genoa, Italy
  9. 9Medical Genetics Unit, Galliera Hospital, Genoa, Italy
  10. 10Consortium for Genomic Technologies, Milan, Italy
  11. 11Medical Oncology Unit A, San Martino-IST Research Hospital, Genoa, Italy
  12. 12Center for Hereditary Tumors, San Martino-IST Research Hospital, Genoa, Italy
  13. 13Laboratory of Rare Hereditary Cancers, San Martino-IST Research Hospital, Genoa, Italy
  1. Correspondence to Dr Paola Ghiorzo, Department of Internal Medicine and Medical Specialties (DiMI), University of Genoa, V.le Benedetto XV, 6, 16129, Genoa, Italy; paola.ghiorzo{at}


Background Most familial pancreatic cancer (FPC) remains unexplained. The identification of individuals with a high genetic risk of developing pancreatic adenocarcinoma (PC) is important to elucidate its biological basis and is critical to better define emerging strategies for the detection of early pancreatic neoplasms.

Patients and methods A series of 225 consecutively enrolled patients with PC were tested for CDKN2A mutations. After personal and family cancer histories of all the patients had been reviewed, a subset of the patients were classified as FPC and were also tested for mutations in PALLD, PALB2, BRCA1 and BRCA2 as FPC candidate genes.

Results The CDKN2A mutation rate in the 225 PC cases was 5.7%. The CDKN2A founder mutations, p.E27X and p.G101W, were predominant, but the mutation spectrum also included p.L65P, p.G67R and two novel, potentially pathogenic variants, promoter variant c.-201ACTC>CTTT and p.R144C. None of the patients with FPC harboured germline mutations in PALLD, PALB2 or BRCA2. One family was positive for the BRCA1 UV variant p.P727L. Strikingly, five of 16 patients with FPC (31%) carried CDKN2A mutations.

Conclusion These findings suggest that a sizeable subset of Italian FPC families may carry CDKN2A mutations. This result may be of value for identifying the best candidates for future PC screening trials in Italy.

  • Pancreatic cancer
  • CDKN2A
  • susceptibility gene
  • PALB2
  • BRCA
  • melanoma
  • genetic screening/counselling
  • genetic epidemiology
  • cancer: dermatological
  • pancreas and biliary tract
  • cancer: colon
  • cancer: gastric
  • cancer: oesophageal
  • genetic screening/counselling
  • clinical genetics
  • genetics
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  • Genoa Pancreatic Cancer Study Group (GPCSG) collaborators: P Ghiorzo, F Belli, L Bonelli, G Borgonovo, F De Cian, A Decensi, P Dulbecco, M Filauro G Fornarini, A Gozza, L Mastracci, F Grillo, S Sciallero, F Papadia, P Queirolo, C Parodi, P Romagnoli, G Sacchi, V Savarino and G Bianchi Scarrà.

  • Funding This study was funded by IRCSS 2007 Italian Ministry of Health DGRST.4/4235-P1.9.A.B, Fondazione CARIGE 2010, PRIN 2008 to GBS.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This case–control study was approved by the ethics committees of the three participating hospitals (San Martino Hospital, Galliera Hospital and National Cancer Institute) in Genoa.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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