For more than a decade, investigators led by William Isaacs, Ph.D., the William Thomas Gerrard, Mario Anthony Duhon and Jennifer and John Chalsty Professor of Urology, have made tremendous progress in discovering major genetic factors linked to an inherited risk of prostate cancer. In fact, a decade before that, Brady investigators led by Isaacs and urologist Patrick C. Walsh, M.D., showed that prostate cancer runs in some families, and that men with a family history of prostate cancer tend to develop it at a younger age; before this, prostate cancer was thought simply to be a really common disease in men.

Some of the risk factors Isaacs and colleagues at Hopkins and elsewhere have discovered include common and rare genetic variants, such as mutations in the genetic sequence called single nucleotide polymorphisms, or SNPs, and in the genes, HOXB13 and BRCA2. In a new study, Isaacs, along with Jianfeng Xu and Brian Helfand at NorthShore Research Institute in Chicago, have looked to see which is more accurate at predicting a man's risk of developing prostate cancer: a family history of the disease, or specific genetic risks, determined by looking at his DNA (specifically, by measuring "SNP profiles" found in blood cells or saliva). "It is well established that men who have a first-degree relative with prostate cancer are at increased risk for prostate cancer," says Isaacs. "What is not known is the degree to which these men are at a higher risk. In the past, each man with a first-degree relative was assumed to have the same increase in risk, depending on how many affected first-degree relatives he had." For example, a man whose father had prostate cancer would be at an elevated risk of developing prostate cancer, but a man whose father, brother, and grandfather had prostate cancer would be at an even higher risk.

In the study, Isaacs, Xu and Helfand examined DNA samples from men with a family history of prostate cancer to determine the number of risky SNPs — altered stretches of DNA — these men inherited. "Interestingly, although most of these men carried more genetic risk factors than men without a family history, some men carried less," says Isaacs. "These men were more likely not to develop prostate cancer than men without a positive family history. Indeed, the results of this study indicate that not all men with a family history of prostate cancer have equivalent risk." In fact, Isaacs continues, there is a wide range of risk, "and this can be estimated through measuring prostate cancer risk SNPs to calculate a genetic risk score." This study has been submitted for publication. Additional studies are needed to validate these findings, he adds, but this study provides a strong basis for developing a simple and inexpensive test to assess differences in prostate cancer risk among sons and brothers of men with prostate cancer. "Such an assessment could be useful in identifying men who would most likely benefit from earlier and more frequent disease screening."