title: Clinical and pathologic features of familial pancreatic cancer.
abstract: BACKGROUND
  Inherited predisposition to pancreatic cancer contributes significantly to its incidence and presents an opportunity for the development of early detection strategies. The genetic basis of predisposition remains unexplained in a high proportion of patients with familial PC (FPC).
  
  
  METHODS
  Clinicopathologic features were assessed in a cohort of 766 patients who had been diagnosed with pancreatic ductal adenocarcinoma (PC). Patients were classified with FPC if they had ≥1 affected first-degree relatives; otherwise, they were classified with sporadic PC (SPC).
  
  
  RESULTS
  The prevalence of FPC in this cohort was 8.9%. In FPC families with an affected parent-child pair, 71% in the subsequent generation were 12.3 years younger at diagnosis. Patients with FPC had more first-degree relatives who had an extrapancreatic malignancy (EPM) (42.6% vs 21.2; P<.0001), particularly melanoma and endometrial cancer, but not a personal history of EPM. Patients with SPC were more likely to be active smokers, have higher cumulative tobacco exposure, and have fewer multifocal precursor lesions, but these were not associated with differences in survival. Long-standing diabetes mellitus (>2 years) was associated with poor survival in both groups.
  
  
  CONCLUSIONS
  FPC represents 9% of PC, and the risk of malignancy in kindred does not appear to be confined to the pancreas. Patients with FPC have more precursor lesions and include fewer active smokers, but other clinicopathologic factors and outcome are similar to those in patients with SPC. Furthermore, some FPC kindreds may exhibit anticipation. A better understanding of the clinical features of PC will facilitate efforts to uncover novel susceptibility genes and the development of early detection strategies.
authors.affiliation: The Kinghorn Cancer Center, Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.
authors.forename: Jeremy L
authors.initials: JL
authors.lastname: Humphris
authors.forename: Amber L
authors.initials: AL
authors.lastname: Johns
authors.forename: Skye H
authors.initials: SH
authors.lastname: Simpson
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Cowley
authors.forename: Marina
authors.initials: M
authors.lastname: Pajic
authors.forename: David K
authors.initials: DK
authors.lastname: Chang
authors.forename: Adnan M
authors.initials: AM
authors.lastname: Nagrial
authors.forename: Venessa T
authors.initials: VT
authors.lastname: Chin
authors.forename: Lorraine A
authors.initials: LA
authors.lastname: Chantrill
authors.forename: Mark
authors.initials: M
authors.lastname: Pinese
authors.forename: R Scott
authors.initials: RS
authors.lastname: Mead
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Gill
authors.forename: Jaswinder S
authors.initials: JS
authors.lastname: Samra
authors.forename: James G
authors.initials: JG
authors.lastname: Kench
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Musgrove
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Tucker
authors.forename: Allan D
authors.initials: AD
authors.lastname: Spigelman
authors.forename: Nic
authors.initials: N
authors.lastname: Waddell
authors.forename: Sean M
authors.initials: SM
authors.lastname: Grimmond
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Biankin
mesh_terms: D000368:Aged; D000428:Alcohol Drinking / Q000453:epidemiology; D002277:Carcinoma / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D021441:Carcinoma, Pancreatic Ductal / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000453:epidemiology; D016889:Endometrial Neoplasms / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology
keywords: epidemiology; hereditary; pancreatic cancer; prognosis