After decades of work, researchers have discovered a new gene variant linked with a higher risk of developing hereditary prostate cancer.
"We've been working in this area for 20 years or so, trying to figure out why prostate cancer clusters in some families with very limited success," said William B. Isaacs, a professor of urology and oncology at Johns Hopkins Medicine and one of the study's authors.
"That's what we think is unique here. It's a genetic change or mutation that affects the protein sequence, and if you carry this variant, you are at an increased risk -- particularly at a young age," he continued.
The study's authors examined DNA from a relatively small pool of families, in which multiple cases of prostate cancer were present. They determined that several had a mutation in the HOXB13 gene, which plays a role in the development of the prostate.
The researchers then looked at a larger pool of more than 5,000 male patients who had sought treatment for prostate cancer at Johns Hopkins and the University of Michigan. They found that 1.4 percent of the men had the mutation -- men who were also far more likely to have one or more first-degree relatives with the disease.
The study, published Wednesday in the New England Journal of Medicine, represents a collaboration between several major universities.
Isaacs cautioned that further research is critical in order to verify the results. In addition, the gene variant likely accounts for only a very small fraction of prostate cancers, he said.
"There's been a lot of controversy around prostate cancer genes," said Dr. James Mohler, chair of urology at the Roswell Park Cancer Institute. "Some of the genes that have been purported to be associated have not held up when others have tested them, and there hasn't been a known reason why they would be associated."
Mohler added that the current study represents an important step in better understanding hereditary prostate cancer -- but only a step.
According to the study's authors, the discovery of the mutation may be most useful in helping researchers better understand how prostate cancer -- which is the number one cancer among men -- develops. It may also help identify a small subset of men who should consider early screening, given that it was found to be more common among men with a family history of early-onset prostate cancer, versus older patients with no family history. There is currently no standard test for prostate cancer, and the efficacy of the PSA blood test has been a source of controversy among professional organizations and health care providers.
For now, however, the practical implications of the study for men are minimal.
"From a biological point of view, this is a very nice study. They've identified that this particular mutation is a predisposing factor to prostate cancer," said. Dr. Peter T. Scardino, chair of the department of surgery at the Memorial Sloan-Kettering Cancer Center. "From a medical practice standpoint, the implications are not very profound, because it's a relatively rare gene."
Scardino said that the HOXB13 variant is not equivalent to BRCA 1 and 2 gene mutations for breast cancer, which significantly increase women's risk of getting the disease. According to the National Cancer Institute, a woman who inherits one of those harmful mutations is approximately five times as likely to develop breast cancer as a woman who does not.
But Scardino said that with further research, the HOXB13 gene mutation might be one of many in a panel that clinicians would screen for in order to determine which men should get prostate cancer testing at younger ages -- which will hopefully help to prevent prostate cancer mortalities.
The Centers for Disease Control estimates that in 2007, the latest year for which data is available, nearly 30,000 men died from the disease.
"We're moving in the right direction," Scardino said. "But we're not there yet."