Gene Mutation May be Linked to Prostate Cancer

Finding opens doors to potential treatments

TUESDAY, Sept. 17, 2002 (HealthDayNews) -- Scientists have discovered another genetic clue that may eventually help doctors treat or even prevent prostate cancer.

The researchers have isolated a gene mutation they believe might play a role in the development of prostate cancer following infection of the gland. The gene, MSR1, a macrophage scavenger receptor, shows mutations in a significant percentage of men with prostate cancer, as well as in families where prostate cancer is hereditary, the researchers say.

MSR1 has previously been linked to the formation of arterial plaques that lead to heart disease, although these findings do not yet suggest a conclusive connection between prostate cancer and arterial plaques, the researchers say.

"We don't want to give people the impression this has immediate impact on how we manage prostate cancer," says William Isaacs, professor of urology and oncology at the Brady Urological Institute and Kimmel Cancer Center at Johns Hopkins University.

"However, this broadens our thinking about what may cause prostate cancer and how the body reacts and recognizes the process of prostate cancer formation," he says.

MSR1 helps white blood cells, called macrophages, clean up cellular debris from bacterial infections and damaged fats or lipids. Macrophage activity is known to increase in the early stages of prostate cancer, and the researchers suspected that some MSR1 mutations might inhibit the ability of macrophages to clean up properly after prostate infections, which produce inflammatory lesions that are often early markers of prostate cancer.

The novelty of this finding is that it's the first time this gene has ever been implicated in a cancer, Isaacs says.

In clinical practice, physicians already closely monitor prostate infection as a precursor to prostate cancer.

"Men often have infections in the prostate," says Dr. Timothy Thompson, professor of urology at Baylor College of Medicine in Houston. "However, the way the immune system reaction to infection develops into cancer is not straightforward," he says.

Thompson adds that in previous studies of macrophage activity in prostate cancer, macrophages sometimes seemed to be beneficial, engulfing prostate cancer cells to kill them. At other times, they seemed to assist cancer cells.

"If the macrophages persist in the prostate, it's probably because there are one or more cancer cells that are resistant. The cancer cells can then use factors secreted by the macrophages to survive and grow more virulent. If these interactions between macrophages and cancer cells are allowed to persist, they could set the stage for cancer," Thompson says.

The new findings were the result of collaborative efforts by researchers from Johns Hopkins University, Wake Forest University, and the National Human Genome Research Institute.

The study was published online yesterday in the journal Nature Genetics.

The study set out to look for gene variations in 159 families with hereditary prostate cancer, and found seven separate mutations of the MSR1 gene in 8 percent of those families.

The study then expanded to men with non-hereditary prostate cancer and found even more significant results. Researchers screened 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.

According to the National Cancer Institute, prostate cancer is found mainly in American men over age 55. The average age of patients at the time of diagnosis is 70. It is much more common in African-American men than in white men, and less common in Asian and Native American men. A man's risk for developing prostate cancer is higher if his father or brother has had the disease.

The collaborators in the new research found mutations in 12.5 percent of African-American men with prostate cancer, compared to 1.8 percent of African-Americans 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.

"We think that even independent of a family history, MSR1 mutations may be an important risk factor," says Isaacs. "The heredity portion of the study looks interesting, but it's not conclusive."

Isaacs also notes that the current research looked only at men of African and European descent, leaving open future inquiry into Hispanics, Asians, and other populations.

What To Do

Learn more about prostate cancer from the National Cancer Institute or the American Cancer Society.

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