Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations and risk for pancreatic adenocarcinoma
Article first published online: 2 NOV 2009
Copyright © 2010 American Cancer Society
Volume 116, Issue 1, pages 203–209, 1 January 2010
How to Cite
McWilliams, R. R., Petersen, G. M., Rabe, K. G., Holtegaard, L. M., Lynch, P. J., Bishop, M. D. and Highsmith, W. E. (2010), Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations and risk for pancreatic adenocarcinoma. Cancer, 116: 203–209. doi: 10.1002/cncr.24697
- Issue published online: 11 JAN 2010
- Article first published online: 2 NOV 2009
- Manuscript Accepted: 9 APR 2009
- Manuscript Revised: 27 MAR 2009
- Manuscript Received: 27 JAN 2009
- Lustgarten Foundation for Pancreatic Cancer Research
- National Cancer Institute grants. Grant Numbers: R01 CA97075, CA116303
- Mayo Clinic SPORE in Pancreatic Cancer. Grant Number: P50 CA 102,701
- pancreatic neoplasms;
- molecular epidemiology;
- cystic fibrosis transmembrane conductance regulator;
- disease-associated mutation
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.
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.
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.
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. Cancer 2010. © 2010 American Cancer Society.