The Johns Hopkins Gazette: September 16, 2002
September 16, 2002
VOL. 32, NO. 3


Heart Disease Gene Linked to Hereditary Prostate Cancer

By Vanessa Wasta
Johns Hopkins Medicine
Johns Hopkins Gazette Online Edition

Researchers at Johns Hopkins, Wake Forest and the National Human Genome Research Institute have implicated mutations in a "heart disease gene" in hereditary prostate cancer. The findings, which offer new evidence that at least some cases of prostate cancer may begin with an infection and inflammatory response, will be published online today in Nature Genetics.

The gene, called macrophage scavenger receptor-1, was identified more than 20 years ago as a factor in plaque formation in arteries, a process that contributes to coronary artery disease, or so-called hardening of the arteries. MSR1 helps immune system cells called macrophages clean up cellular debris from bacterial infections and damaged fats or lipids. Macrophage activity has been known to increase in the early stages of prostate cancer, and the Hopkins investigators suspected that some MSR1 mutations might inhibit the ability of macrophages to clean up properly after prostate infections, producing inflammatory lesions that are often markers of prostate cancer.

This is the first time that MSR1 has been linked to cancer, and it may tie infections and similar environmental exposures to cancer of the prostate in a way that we haven't thought about before, says William B. Isaacs, a professor of urology and oncology at the Brady Urological Institute and Kimmel Cancer Center at Johns Hopkins.

Hunting for gene mutations that increase one's risk for prostate cancer, researchers screened 159 families with hereditary prostate cancer and found seven different mutations in the MSR1 gene in 13 families, or about 8 percent of the hereditary prostate cancer families studied.

To compare the impact of this gene in men with nonhereditary sporadic prostate cancer, the researchers screened another 731 men, 365 with prostate cancer and 366 without. Overall, the research team found that MSR1 mutations were about seven times more common in men with prostate cancer than in those without. Mutations were found in 12.5 percent of African-American men with prostate cancer as compared to 1.8 percent without the disease. In men of European descent, 4.4 percent of men with prostate cancer and less than 1 percent without prostate cancer had MSR1 mutations. "This genetic evidence suggests that MSR1 may play an important role in prostate cancer susceptibility in both African-American men and men of European descent," says Jianfeng Xu, of the Center for Human Genomics at Wake Forest.

Isaacs and colleagues will conduct additional studies to uncover the pathway that the MSR1 gene controls and confirm the prevalence of MSR1 mutations in larger studies.

The research was funded by the National Cancer Institute; the Department of Defense; CaPCURE; Fund for Research and Progress in Urology; and the William Thomas Gerrard, Mario Anthony Duhon, Jennifer and John Chalsty Professorship in Urology.

Participants in this research from Hopkins are Sarah Isaacs, Charles Ewing, Dennis Faith, Jill Johnson, Hiroyoshi Suzuki, Piroska Bujnovszky, Kathleen Wiley, Angelo DeMarzo, G. Steven Bova, Alan Partin and Patrick C. Walsh.

Related Web sites
Johns Hopkins Brady Urological Institute
Johns Hopkins Kimmel Cancer Center