Women’s Cancer Research Fund

January 12, 2012 by staff 

Women’s Cancer Research Fund, Scientists have known that prostate cancer runs in families for about 30 years. What’s at the heart of this hereditary pattern has remained a mystery, though, until now.

Researchers have discovered a genetic mutation associated with prostate cancer that’s passed down among families.

A man who inherits this alteration has an enormously higher – a 10-20 times greater – risk of developing the most common non-skin cancer in men.

If prostate cancer runs in your family, talk with your doctor.
The research team that uncovered this hereditary genetic mutation was led by investigators at the Johns Hopkins University School of Medicine and the University of Michigan (U-M) Health System.

“This is the first major genetic variant associated with inherited prostate cancer,” said senior author Kathleen A. Cooney, M.D., professor of internal medicine and urology at the U-M Medical School

Researchers worked with John Carpten, Ph.D., at the Translational Genomics Research Institute (TGen) in Phoenix. He used the Institute’s most advanced technology to sequence more than 200 genes in an area of the human chromosome region known as 17q21-22, a region Dr. Cooney had previously identified working with Ethan Lange, Ph.D., of the University of North Carolina on the U-M Prostate Cancer Genetics Project

Samples were taken from the youngest men with prostate cancer from 94 families with a history of the disease. These men had been enrolled in other Johns Hopkins and U-M studies.

The same mutation in the HOXB13 gene was found in 18 men with prostate cancer from four different families. This gene is heavily involved in the development of the prostate in fetuses and the function of the gland later in life.

Jianfeng Xu, Ph.D., and Lilly Zheng, Ph.D., at Wake Forest University looked for this same variant in 5,100 men who had received care prostate cancer at either Johns Hopkins or U-M.

The genetic rearrangement was seen in 1.4 percent of the men, all of whom were considerably more likely to have a first-degree relative with prostate cancer. Researchers also looked for the mutation in 1,400 men who didn’t have prostate cancer, and only one man carried it. Men enrolled in studies examining early-onset and hereditary prostate cancer were also studied.

“We found that the mutation was significantly more common in men with a family history and early diagnosis compared with men diagnosed later, after age 55, without a family history.

The difference was 3.1 percent versus 0.62 percent,” Dr. Cooney said in a news release reporting the results.

Co-author Patrick Walsh, M.D., professor of urology at Johns Hopkins University School of Medicine, had originally found that prostate cancer runs in families back in the 1980s.

“We had never seen anything like this before. It all came together to suggest that this single change may account for at least a portion of the hereditary form of the disease,” Dr. Walsh said.

The study’s other senior author, William B. Isaacs, Ph.D., professor of urology and oncology at the Johns Hopkins University School of Medicine, says this is just the beginning. An animal model needs to be tested.

“Future DNA sequencing may also identify additional rare variants that contribute to prostate cancer risk in families,” Isaacs adds.

After more research, it may be that men with a family history of prostate cancer can be tested for this genetic mutation in much the same way women are tested for BRCA mutations to assess their risks of developing breast cancer.

Findings from this study were published in the January 12, 2012 issue of the New England Journal of Medicine.

The William Gerrard, Mario Duhon, John and Jennifer Chalsty, P. Kevin Jaffe and Patrick C. Walsh Cancer research fund supported this research.

Prostate Cancer
Each year in the United States, over 200,000 men will be diagnosed with prostate cancer. Unfortunately, 32,000 of them will succumb to the disease, making it the third most common cause of death from cancer in men of all ages and the most common cause of death from cancer in men over age 75. However, due to improved detection and treatment, there are over 2 million men in the United States who are currently prostate cancer survivors.

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