The cystic fibrosis transmembrane regulator is abnormal in 4 or 5% of Caucasians. A single defective gene however causes no apparent harmful effects. Based on Dr. Abraham's discovery that the CFTR gene product acts as a transmembrane ATP transporter, we hypothesized that patients and animals that have CFTR heterozygosity will have a reduced propensity for the development of aggressive breast cancers. We have shown that heterozygous knockout mice at the CFTR locus grow breast cancers at a reduced rate and tumors in these animals have reduced aggressiveness compared to the wild type animals. Likewise, the homozygous knockouts had a severly reduced ability to grow breast cancers. It appears that this is due to the elevated ATP found in the blood of the heterozygous and homozygous knockout animals. We are therefore examining human Caucasian patients with breast cancer to determine if CFTR abnormalities are occurring at a reduced rate in these patients. We will also be measuring blood ATP levels in patients with breast cancer to determine if it is lower than expected. Finally, we are in the process of developing a similar protocol for screening patients with prostate cancers. A total of 420 are to be accrued with each disease.
