Inherited genetic links to prostate cancer discovered

By Dr. Ananya Mandal, MDAug 17 2011

Researchers from the U.S. and Sweden have linked five inherited genetic mutations to the development of a particularly aggressive and deadly form of prostate cancer. They suggest that these findings could someday lead to development of an easy-to-administer blood test to screen for such mutations to help physicians assess the long-term risk faced by newly diagnosed prostate cancer patients.

“The ability to distinguish patients at elevated risk for having aggressive, life-threatening prostate cancer at the time of diagnosis could improve care for the subset of cases most likely to benefit from aggressive therapy and help avoid over-treatment of patients whose tumors are likely to remain indolent,” the study team, led by Janet L. Stanford, co-director of the Fred Hutchinson Cancer Research Center's program in prostate cancer research, reported in the Aug. 16 online edition of Cancer Epidemiology, Biomarkers and Prevention.

Stanford said, “Biomarkers that could distinguish between patients with indolent vs. more aggressive tumors are urgently needed…The panel of markers we've identified provides the first validated evidence that inherited genetic variants play a role in prostate cancer progression and mortality. Ultimately these markers could be used in the clinic, along with other known predictors that are used to assess tumor aggressiveness, such as a high Gleason score, to identify men with a high-risk profile.”

The authors, looking for genetic differences that could highlight risk differences, gathered blood samples from more than 1,300 prostate cancer patients living in the Seattle region. All were between the ages of 35 and 74 when diagnosed. DNA analyses of the samples were compiled with those of nearly 2,900 Swedish prostate cancer patients.

The results revealed that five single-letter mutations (or SNPs) were isolated among the patients' “DNA alphabet” as having a significant bearing on prostate cancer progression in terms of affecting cell death, tumor growth, inflammation, androgen hormone levels, blood-vessel development and bone density. The five markers -- LEPR, RNASEL, IL4, CRY1 and ARVCF -- are single-nucleotide polymorphisms, or SNPs, DNA variations that may be linked to disease.

Patients found to have at least four out of the five cited SNP mutations appeared to face a 50 percent higher risk for dying from their disease compared with those who carried two or fewer of the mutations.

William Phelps, program director of translational and preclinical cancer research at the American Cancer Society, said, “If the treatments we had for prostate cancer were very tolerable or very safe you would probably treat everybody,” he explained. “But the treatments we have available today are less than ideal…So certainly we can try to improve treatment. But at the same time we can also try to improve ways to identify patients who are more likely to progress rapidly from those likely to be very slow going, so we can reserve treatment for only those instances when it's really necessary. If there are markers that better define the men whose cancer is most likely to progress, that would certainly prove very useful in the current climate.”

Prostate cancer kills about 32,000 men in the United States each year, but is the most commonly diagnosed of all male cancers with 240,890 new cases each year, said the National Cancer Institute. More studies are planned to examine other patient populations. African-Americans are twice as likely to die from prostate cancer as whites, according to the NCI, which noted that the disease is common in North America and northwestern Europe, but less so in Asia and South America.