Fast/Slow Telomere Shortening Predicts Cancer

May 1, 2015
Fast/Slow Telomere Shortening Predicts Cancer
Telomeric DNA is subject to attrition due to aging, and it accelerates early in cancer. Such attrition, however, slows three to four years before cancer is typically diagnosed. [molekuul.be/Fotolia]

Telomere length hasn’t been a reliable yardstick for measuring the progress of cancer. Because cancer cells divide frequently, and because telomeres shorten with repeated cell division, you might expect cancer cells to age rapidly, and then expire. Yet cancer cells often compensate by making more telomerase enzyme, which prevents the telomeres from getting even shorter. All the same, many cancer cells have very short telomeres. In fact, telomeres in persons developing cancer can look as much as 15 years chronologically older than those of people who are not developing the disease.

To resolve these seemingly contradictory observations, researchers from Northwestern University and Harvard University tracked telomere changes over a fairly long period of time, checking telomere lengths in blood cells at multiple time points. Doing so allowed these researchers to detect a pattern that previous investigators had overlooked. Telomere length shortens dramatically at first, and then stabilizes. And this switch, from fast to slow, occurs three to four year before cancer is typically diagnosed.

The timing of the fast/slow changeover may be telling. That is, it may indicate when cancer hijacks the cell's aging process.

Understanding the pattern of telomere shortening could ultimately yield a new biomarker to predict cancer development with a blood test. This point was emphasized by one of the researchers, Lifang Hou, M.D., Ph.D., a professor of preventive medicine at Northwestern University Feinberg School of Medicine: “Because we saw a strong relationship in the pattern across a wide variety of cancers, with the right testing these procedures could be used to eventually diagnose a wide variety of cancers.”

Dr. Hou is the lead author of an article ("Blood Telomere Length Attrition and Cancer Development in the Normative Aging Study Cohort") that resulted from the Northwestern/Harvard study. This article, which appeared online April 30 in EBioMedicine, describes how scientists took multiple measurements of telomeres over a 13-year period in 792 persons, 135 of whom were eventually diagnosed with different types of cancer, including prostate, skin, lung, leukemia, and others.

"[Relative] to approaching cancer diagnosis, age-adjusted BTL [blood telomere length] attrition decelerated in cancer cases, ultimately yielding significantly elongated BTL and suggesting that critical BTL shortening may contribute to cancer initiation which then, in turn, activates telomere maintenance mechanisms to compensate and further promote cancer," wrote the authors of the article. "Thus, our results may help explain the inconsistent results of previous studies and provide more insight into using BTL as an early detection biomarker of cancer."

The Northwestern/Harvard study is believed to be the first to look at telomere length at more than one time point before diagnosis. That's significant because cancer treatment can shorten telomeres. Post treatment, it's uncertain whether their length has been affected by the cancer or the treatment.

"This likely explains why the previous studies have been so inconsistent," Dr. Hou noted. "We saw the inflection point at which rapid telomere shortening stabilizes. We found cancer has hijacked the telomere shortening in order to flourish in the body."

If scientists can identify how cancer hijacks the cell, Dr. Hou added, perhaps treatments could be developed to cause cancer cells to self-destruct without harming healthy cells.