CFTR deltaF508 carrier status, risk of breast cancer before the age of 40 and histological grading in a population-based case-control study.
There has been recent interest in the risk of various cancers in cystic fibrosis (CF) patients and carriers of cystic fibrosis transmembrane conductance regulator (CFTR) mutations. It has been proposed that a CFTR mutation may protect against breast cancer, based on evidence that elevated extracellular adenosine triphosphate (ATP) is known to inhibit breast cancer cell line growth and that CFTR pumps ATP out of epithelial cells. A CFTR mutation would therefore result in higher concentrations of serum ATP. A CFTR knockout mouse model had high serum concentrations of ATP and showed reduced breast tumour implantibility and decreased breast cancer growth rates. We have evaluated the relationship between the deltaF508 CFTR mutation and the risk of breast cancer before the age of 40. The deltaF508 CFTR mutation carrier rate in 272 cases (2.2%) was no different from the carrier rate observed in 171 controls (1.8%). If there was a protective effect resulting from the postulated elevation in serum ATP levels, tumours arising in deltaF508 CFTR carriers would have been expected to be generally less aggressive. When the histological features of the breast cancers with a deltaF508 CFTR mutation were reviewed and graded using a combined architectural and cytological grading system, all were found to be grade III, poorly differentiated tumours, contrary to the predictions. A combination of our data with other large population-based samples of cases and controls is required to resolve this issue.
Department of Pathology, Peter MacCallum Cancer Institute, Melbourne, Australia. msouthey@pmci.unimelb.edu.au
M C
MC
Southey
L
L
Batten
C R
CR
Andersen
M R
MR
McCredie
G G
GG
Giles
G
G
Dite
J L
JL
Hopper
D J
DJ
Venter
D000255:Adenosine Triphosphate / Q000097:blood; D000328:Adult; D000367:Age Factors; D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1 / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D016017:Odds Ratio; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics
D024682:BRCA2 Protein; C505032:CFTR protein, human; D009363:Neoplasm Proteins; D014157:Transcription Factors; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000255:Adenosine Triphosphate