By Charlie Schmidt
The prostate-specific antigen (PSA) test can generate more questions than answers. If your level is high, it could mean that your prostate is enlarged or infected. It could mean that you have prostate cancer. It could also mean that your prostate gland is healthy, since normal PSA levels vary widely from one man to another. Because of this variability, PSA tests often lead to prostate biopsies among men who don’t have cancer. That’s why doctors would prefer that only men at high risk for prostate cancer have PSA tests. A study published this month in the journal European Urology suggests that men who have defects in a cancer-suppressing gene known as BRCA are at high risk for aggressive prostate tumors, and so could benefit from PSA testing.
The BRCA gene comes in two forms, BRCA1 and BRCA2. Both make proteins that repair the genetic damage that all cells experience thousands of times a day. When these genes carry the wrong code, they don’t work as intended. This miscoding can be passed from one generation to another. “Bad” BRCA genes (BRCA-positive) lose their DNA-fixing ability. As a result, genetic damage can accumulate to the extent that healthy cells turn cancerous.
In women, miscoded BRCA genes are well-known risk factors for breast and ovarian cancer. This new study shows that they can also pose problems for men. The authors of the study recommend that men with miscoded BRCA genes have routine PSA tests.
“PSA might detect early stage cancers in these men while they’re still curable,” says William Isaacs, Ph.D., a professor of urology at Johns Hopkins University School of Medicine in Baltimore, who was not involved in the study.
An international team of researchers has been following nearly 2,500 men as part of a study called IMPACT. It includes some men with miscoded BRCA genes and others with normal BRCA genes. Of these, 199 had high PSA levels, of whom 162 had prostate biopsies to look for prostate cancer. Biopsies revealed prostate cancer in 59 men. The cancer risk for BRCA-positive men was greater than it was for men with normal BRCA genes. Equally important, men in the BRCA-positive group—especially those with BRCA2 mutations—tended to have more high-grade, aggressive tumors.
What remains unclear is which men should have their BRCA genes checked. Men whose mothers or sisters have or had breast or ovarian cancer might consider BRCA testing. But widespread use of BRCA testing “will require significantly more data,” says prostate cancer specialist Dr. Marc B. Garnick, the Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, and Editor in Chief of Harvard Medical School’s 2014 Annual Report on Prostate Diseases. “Nevertheless, BRCA information could be useful, especially if it provides for other treatment options for men that might not be considered in its absence.”