title: Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations and risk for pancreatic adenocarcinoma.
abstract: BACKGROUND
  Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are common in white persons and are associated with pancreatic disease. The purpose of this case-control study was to determine whether CFTR mutations confer a higher risk of pancreatic cancer.
  
  
  METHODS
  In a case-control study, the authors compared the rates of 39 common cystic fibrosis-associated CFTR mutations between 949 white patients with pancreatic adenocarcinoma and 13,340 white controls from a clinical laboratory database for prenatal testing for CFTR mutations. The main outcome measure was the CFTR mutation frequency in patients and controls.
  
  
  RESULTS
  Overall, 50 (5.3%) of 949 patients with pancreatic cancer carried a common CFTR mutation versus 510 (3.8%) of 13,340 controls (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.04-1.89; P = .027). Among patients who were younger when their disease was diagnosed (<60 years), the carrier frequency was higher than in controls (OR, 1.82; 95% CI, 1.14-2.94; P = .011). In patient-only analyses, the presence of a mutation was associated with younger age (median 62 vs 67 years; P = .034). In subgroups, the difference was seen only among ever-smokers (60 vs 65 years, P = .028). Subsequent sequencing analysis of the CFTR gene detected 8 (16%) compound heterozygotes among the 50 patients initially detected to have 1 mutation.
  
  
  CONCLUSIONS
  Carrying a disease-associated mutation in CFTR is associated with a modest increase in risk for pancreatic cancer. Those affected appear to be diagnosed at a younger age, especially among smokers. Clinical evidence of antecedent pancreatitis was uncommon among both carriers and noncarriers of CFTR mutations.
authors.affiliation: Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA. mcwilliams.robert@mayo.edu
authors.forename: Robert R
authors.initials: RR
authors.lastname: McWilliams
authors.forename: Gloria M
authors.initials: GM
authors.lastname: Petersen
authors.forename: Kari G
authors.initials: KG
authors.lastname: Rabe
authors.forename: Leonard M
authors.initials: LM
authors.lastname: Holtegaard
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Lynch
authors.forename: Michele D
authors.initials: MD
authors.lastname: Bishop
authors.forename: W Edward
authors.initials: WE
authors.lastname: Highsmith
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000235:genetics*; D012306:Risk; D012907:Smoking
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator