title: Importance of age of onset in pancreatic cancer kindreds.
abstract: BACKGROUND
  Young-onset cancer is a hallmark of many familial cancer syndromes, yet the implications of young-onset disease in predicting risk of pancreatic cancer among familial pancreatic cancer (FPC) kindred members remain unclear.
  
  
  METHODS
  To understand the relationship between age at onset of pancreatic cancer and risk of pancreatic cancer in kindred members, we compared the observed incidence of pancreatic cancer in 9040 individuals from 1718 kindreds enrolled in the National Familial Pancreas Tumor Registry with that observed in the general US population (Surveillance, Epidemiology, and End Results). Standardized incidence ratios (SIRs) were calculated for data stratified by familial vs sporadic cancer kindred membership, number of affected relatives, youngest age of onset among relatives, and smoking status. Competing risk survival analyses were performed to examine the risk of pancreatic cancer and risk of death from other causes according to youngest age of onset of pancreatic cancer in the family and the number of affected relatives.
  
  
  RESULTS
  Risk of pancreatic cancer was elevated in both FPC kindred members (SIR = 6.79, 95% confidence interval [CI] = 4.54 to 9.75, P < .001) and sporadic pancreatic cancer (SPC) kindred members (SIR = 2.41, 95% CI = 1.04 to 4.74, P = .04) compared with the general population. The presence of a young-onset patient (<50 years) in the family did not alter the risk for SPC kindred members (SIR = 2.74, 95% CI = 0.05 to 15.30, P = .59) compared with those without a young-onset case in the kindred (SIR = 2.36, 95% CI = 0.95 to 4.88, P = .06). However, risk was higher among members of FPC kindreds with a young-onset case in the kindred (SIR = 9.31, 95% CI = 3.42 to 20.28, P < .001) than those without a young-onset case in the kindred (SIR = 6.34, 95% CI = 4.02 to 9.51, P < .001). Competing risk survival analyses indicated that the lifetime risk of pancreatic cancer in FPC kindreds increased with decreasing age of onset in the kindred (hazard ratio = 1.55, 95% CI = 1.19 to 2.03 per year). However, youngest age of onset for pancreatic cancer in the kindred did not affect the risk among SPC kindred members.
  
  
  CONCLUSIONS
  Individuals with a family history of pancreatic cancer are at a statistically significantly increased risk of developing pancreatic cancer. Having a member of the family with a young-onset pancreatic cancer confers an added risk in FPC kindreds.
authors.affiliation: Department of Pathology, Sol Goldman Pancreatic Cancer Research Center at Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.
authors.forename: Kieran A
authors.initials: KA
authors.lastname: Brune
authors.forename: Bryan
authors.initials: B
authors.lastname: Lau
authors.forename: Emily
authors.initials: E
authors.lastname: Palmisano
authors.forename: Marcia
authors.initials: M
authors.lastname: Canto
authors.forename: Michael G
authors.initials: MG
authors.lastname: Goggins
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Hruban
authors.forename: Alison P
authors.initials: AP
authors.lastname: Klein
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000453:epidemiology* / Q000235:genetics; D018426:SEER Program; D014481:United States / Q000453:epidemiology