Biomarker in Blood May Be Associated With Risk of Aggressive Prostate Cancer

NATIONAL HARBOR, Md. — Men with short-ended chromosomes in the immune cells in their blood were at increased risk for aggressive prostate cancer compared with men with long-ended chromosomes in blood immune cells, according to results presented here at the 12th Annual AACR International Conference on Frontiers in Cancer Prevention Research, held Oct. 27–30.

Elizabeth A. Platz, Sc.D., M.P.H.

Currently, there is no way to predict which men are at risk for developing aggressive prostate cancer, and identifying a biomarker for this is an active area of research. This study indicates that the length of telomeres in blood leukocytes could be a biomarker of risk for aggressive prostate cancer.

“Telomeres are repeated sequences of genetic material that protect the ends of our chromosomes,” said Elizabeth A. Platz, Sc.D., M.P.H., a professor in the Department of Epidemiology at Johns Hopkins Bloomberg School of Public Health in Baltimore, Md. “In cancers, telomeres are often shortened, making the chromosomes less stable and more prone to damage.

“In research that we published earlier this year in the AACR journal Cancer Discovery, we found that men with prostate cancer who had high variability in the length of telomeres from one prostate cancer cell to another and shorter telomere length in prostate cancer-associated stromal cells were substantially more likely to develop metastases or die of their disease compared with men with prostate cancer harboring neither of these characteristics,” explained Platz, who is also a professor in the Department of Urology at the James Buchanan Brady Urological Institute at Johns Hopkins School of Medicine, and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.

According to Platz, for the current study, she and her colleagues wanted to look at a more easily accessible tissue, the blood, and look at earlier time points to determine whether telomere length could predict a man’s future risk of prostate cancer.

They analyzed DNA from immune cells called leukocytes isolated from blood samples provided from 1993 to 1995 by men who enrolled in Harvard’s Health Professionals Follow-up Study. The researchers studied 441 men who later developed prostate cancer, with a mean time from blood draw to diagnosis of three years, and 421 men who did not develop prostate cancer during follow-up.

Relative telomere length was measured in all study participants’ blood leukocytes by quantitative PCR and categorized into tertiles based on the distribution of telomere length in the men who did not develop prostate cancer. The researchers found that among the men who developed prostate cancer, those with the shortest telomeres in their leukocytes at blood draw—those with telomere lengths in the bottom two tertiles—were more than twice as likely to have developed aggressive prostate cancer compared with those men who had the longest telomeres—telomeres lengths in the top tertile.

When the researchers narrowed their analysis down to men who smoked, or had smoked in the past, they found that those with the shortest telomeres in their blood leukocytes were more than four times as likely to have gone on to develop aggressive prostate cancer.

“Our studies on telomeres and prostate cancer risk and prognosis are the products of successful team science,” said Platz.

“We don’t yet know why having short telomeres in blood leukocytes seems to be associated with risk of aggressive prostate cancer,” said Platz. “It may tell us about a person’s exposure to factors that increase their risk of prostate cancer, or it may be an indication of an inherent inability to maintain telomere length, which could put them at increased risk for this disease. If so, it might be that measuring telomere length in blood leukocytes could even predict risk of many different forms of cancer.”

This study was funded by the Department of Defense and the National Cancer Institute. Platz has declared no conflicts of interest.