Scientists find genetic mutation associated with early prostate cancer

Jan. 12, 2012
Scientists find genetic mutation associated with early prostate cancer
Jay Price | McClatchy Newspapers

last updated: January 12, 2012 08:00:57 AM

CHAPEL HILL, N.C. — A team of scientists has found a genetic mutation strongly associated with prostate cancers that occur at unusually early ages and among people with a family history of the disease.

Men are often diagnosed with prostate cancer late in life, but it develops so slowly that they often die of something else. Those who get the cancer while relatively young, though, are at significantly higher risk of dying from the disease.

That lends weight to the significance of the new findings, published Thursday in the New England Journal of Medicine.

It's the first high-risk genetic mutation found to be associated with the disease, said Ethan Lange, an associate professor of genetics and biostatistics at the University of North Carolina-Chapel Hill and a member of the university's Lineberger Comprehensive Cancer Center.

Nearly a quarter of a million American men are expected to be diagnosed with the disease this year.

If the results are borne out by larger studies, the mutation could become a valuable genetic screening tool, particularly for men with family histories of early-onset prostate cancer, said Lange, a first author of the research paper.

It also could one day lead to better, targeted treatments for cancers tied to the mutation.

Lange cautioned that the links found between the mutation and prostate cancer were strictly statistical. They point to the need for more elaborate studies to determine whether the mutation actually causes prostate cancer and to the need for larger studies to better estimate the chances that a man will be born with the mutation and the probability that a man having it will develop prostate cancer.

Also, no relationship was observed between the severity of the disease and the mutation, he said.

The study began when researchers looked at the genetic material of 94 unrelated men from families that had a history of multiple cases of prostate cancer. They found four cases in which the men had the genetic mutation. That piqued their interest because the mutation has been shown in studies using mice to be important to prostate development.

They then checked 14 other men who had been diagnosed with prostate cancer in those four families, and all were found to carry the mutation. That made 18 men from four families, all with the cancer, and all of them carrying the mutation.

The researchers then decided to study a larger group: 5,083 men with prostate cancer and a control group of 1,401 who had been tested and found not to have the disease.

The mutation was found in just one of the men who didn't have cancer, but in 72 of those who did, or 1.4 percent.

Though the percentage is small, it meant that among the men examined in the study the mutation was 20 times more common than in those without cancer.

And it was most common - though still rare - among those who both were diagnosed before turning 56 years old and who had a family history of prostate cancer.

The genetics of prostate cancer have been hard to unravel, said James P. Evans, Bryson Distinguished Professor of Genetics in the UNC School of Medicine and an expert in cancer genetics. He called the new findings welcome progress.

"While fewer than one percent of Caucasian men carry the described mutation in this particular gene, for those men who do carry it, the increased risk for developing prostate cancer is likely greater than for any previous mutation found to date, "Evans said. "Larger follow-up studies will be necessary to understand the importance of this finding for prostate cancer, and it remains to be seen whether this mutation is associated with other cancers."

Evans was not involved in the study.

The research team has been seeking genetic links to prostate cancer for 17 years, and in 2003 had identified a region of DNA material that seemed a likely place to study.

Only recently, though, have advances in technology cut the cost of sequencing genetic material to the point that researchers could take a closer look, Lange said. That's where they found the mutation.

The bulk of the genetic testing for the study was funded by the American Recovery and Reinvestment Act, via a $225,000 grant to the University of Michigan, he said.

The research team includes scientists at Johns Hopkins University, the University of Michigan Health System, Wake Forest University and the Translational Genomics Research Institute in Phoenix, Ariz.

Prostate Cancer

Cancer of the prostate, a gland in the male reproductive system found below the bladder, typically begins to develop among men over 50 and is common among elderly men. About two-thirds of cases grow slowly, and many men harbor the disease without symptoms or treatment for decades, and die of other causes.

There are fast-growing types, though, that can kill much more quickly, often after spreading to surrounding bone or the lymph system.

The National Cancer Institute estimates that 241,740 men will be diagnosed with prostate cancer in the U.S. this year and 28,170 will die of it.

Prostate cancer is one of the most curable cancers, when detected early. In particular, black men 40 years and older, white men with a family history of cancer who are 40 and older, and white men 50 and older are encouraged to have prostate exams.