What are your odds of getting prostate cancer? Even if you do everything you can think of to help prevent it — for example, if you load up on fruits and vegetables, avoid red meat, and faithfully drink a glass of red wine several times a week — there's one thing you can't change: Your family history.

"Having prostate cancer in the family is one of the strongest risk factors yet identified for prostate cancer," says William T. Isaacs, Ph.D., the William Thomas Gerrard, Mario Anthony Duhon and Jennifer and John Chalsty Professor of Urology. "Although environmental factors such as diet are also important, it's clear from multiple studies that inherited genetic factors play a critical role in determining prostate cancer risk."

Isaacs and colleagues have been studying familial prostate cancer for more than 14 years, and have scrutinized the genes of more than 200 families. Their intensive genetic work has led them to discover several genes that increase a man's risk for prostate cancer. They've found increasing evidence that inflammation plays an important role, and so do critical variations in the genes involved in developing cancer. And yet, they believe, they've only scratched the surface—that there are many more prostate cancer susceptibility genes out there, waiting to be discovered.

The best way to identify and characterize these new genes is to study the families who, unfortunately, have been hardest-hit by the disease, with multiple relatives affected over several generations. To achieve a "critical mass" of families, and to maximize the information gathered from such families worldwide, Isaacs and colleagues have established a collaborative research network for scientists working in this area, called the ICPCG — International Consortium for Prostate Cancer Genetics. Isaacs is the ICPCG's chairman, and the principal investigator of a federally funded grant supporting this group. Together, the consortium's 14 research teams have obtained a much larger pool of prostate cancer families — more than 2,000 — for genetic analyses.

In one of the largest studies of its kind ever performed, the ICPCG recently combined genetic mapping data from more than 1,200 families with hereditary prostate cancer (with at least three first-degree relatives affected) to pinpoint the regions of the genome most likely to harbor prostate cancer susceptibility genes. The scientists found that a region on chromosome 22 is most likely the home of a gene that raises the inherited risk of prostate cancer in general.

“Having prostate cancer in the
family is one of the strongest risk
factors yet identified.”

Also, in a separate study, they identified regions on chromosomes 6, 11 and 20 as the locations of genes that make a man more likely to develop aggressive prostate cancer. "This group of families is particularly interesting," notes Isaacs. "Only about 10 percent of all prostate cancer families are in this category, so their study can only be performed by large combined analyses." Because of these studies, he adds, "we now have the critical information necessary to identify these important prostate cancer susceptibility genes." Isaacs and colleagues believe that finding these genes will have a huge impact on our understanding of prostate cancer, how best to treat it, and even how to help prevent it.