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Cystic fibrosis transmembrane conductance regulator ( CFTR ) gene mutations and risk for pancreatic adenocarcinoma
Author(s) -
McWilliams Robert R.,
Petersen Gloria M.,
Rabe Kari G.,
Holtegaard Leonard M.,
Lynch Pamela J.,
Bishop Michele D.,
Highsmith W. Edward
Publication year - 2009
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.24697
Subject(s) - cystic fibrosis transmembrane conductance regulator , medicine , cystic fibrosis , pancreatic cancer , odds ratio , pancreatic disease , gastroenterology , mutation , heterozygote advantage , adenocarcinoma , cancer , oncology , genotype , pancreas , gene , genetics , biology
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. Cancer 2010. © 2010 American Cancer Society.