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Gene variation increases prostate cancer risk

by Ruth SoRelle, MPH

Michael Ittmann, MD, PhD

A frequently occurring variation in a gene called the fibroblast growth factor receptor-4 can increase both the risk of developing prostate cancer and the virulence of the disease itself, said Baylor College of Medicine researchers in a recent report in the journal Clinical Cancer Research.

The variation, a single change in three letters of the DNA alphabet that directs production of an amino acid, can increase by fourfold the risk of developing prostate cancer in people who have two copies of the gene variant called a polymorphism, said Michael Ittmann, MD, PhD, BCM professor of pathology. Approximately 4 percent of the white population carries two copies of this variant, he said. African-Americans are much less likely to have the variant, a factor that needs further study.

"This is probably an equivalent risk to BRCA2 in prostate cancer," said Ittmann. BRCA2 is a gene that increases the risk of developing breast and ovarian cancer in women; men with this gene are at risk of developing prostate cancer.

While the finding needs to be confirmed by other laboratories, Ittmann said the findings in his laboratory have a strong statistical basis. In fact, having just one copy of the variant gene increases the risk that prostate cancer will spread to a pelvic lymph node or that biochemical markers indicating a recurrence will increase a so-called PSA (prostate-specific antigen) recurrence. Approximately 50 percent of the white population carries at least one copy of the gene variant.

As part of their study, Ittmann and his colleagues extracted the genetic material from benign tissues in 329 prostate cancer patients. Forty-five of these patients were African American and the remainder white. The findings in their DNA were compared to 97 healthy white men and 94 healthy African-Americans.

This gene variation also affects breast and colon cancers as well as some sarcomas.

"I think the full implications of this gene are not clear," said Ittmann. "Could we integrate knowledge about whether a man carries this gene into treatment plans? We will need to carry out further studies to test this idea."

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