ORLANDO, FL-Three decades after the discovery of telomeres, researchers are beginning to explore the role these chromosome shields might play in promoting and preventing cancer. AACR 2010-2011 President Elizabeth H. Blackburn, PhD, says that now is the time to learn more about the impact of telomeres on mutations.
"More and more, we have to think about prevention," said Dr. Blackburn, who was awarded the Nobel Prize in Physiology or Medicine in 2009 with Carol Greider and Jack Szostak for the discovery of how chromosomes are protected by telomeres and telomerase. "Telomeres protect cells and when they get short, they lose this protective ability."
Dr. Blackburn, the Morris Herztein Professor of Biology and Physiology in the Department of Biochemistry and Biophysics at the University of California, San Francisco, devoted her Presidential Address to the topic of telomeres and telomerase, calling them "double-edged swords in cancer," and was also one of three panelists who discussed advances in telomere research at an AACR news conference.
Telomeres are repetitive DNA sequences at the ends of chromosomes that protect the strands from fraying during duplication, much like aglets protect shoelaces. The discovery of telomeres solved the puzzle of how cells could replicate multiple times without degrading.
The strength of telomeres depends on their length, Dr. Blackburn explained. Scientists have known for more than a decade that short telomeres on immune cells are markers of aging. More recently it has been shown that short telomeres also are associated with a variety of diseases including some forms of cancer. Yet, for unknown reasons, telomeres vary in length among people of the same age and appear to shorten and lengthen in response to certain stimuli. Scientists now are trying to understand why.
Emotions Linked to Telomere Length
Dr. Blackburn's pioneering studies focused on the effects of emotional health on telomere length. She first reported the connection in 2004 following a study showing shortened telomeres in the immune cells of female caregivers of chronically ill children. Her team's recent study of patients with post-traumatic stress disorder reaffirmed that link.
"In patients with post-traumatic stress disorder, we saw a relationship between childhood trauma and shortened telomeres," said Jue Lin, PhD, Assistant Research Biochemist in Dr. Blackburn's lab, who presented the research as a poster study and was interviewed after the meeting. "Stress levels change in correlation with telomere length change."
The team also found evidence that regular, vigorous exercise preserves telomere length in caregivers facing long-term stress, findings that were reported in May 2010 in PLoS One.
Also speaking at the news conference, Edward Nelson, MD, Interim Chief of Hematology Oncology at the University of California Irvine School of Medicine, who studied the effects of counseling on telomere length in patients with cervical cancer.
"We chose a population we thought had the greatest potential for improvement in quality of life," he said. "Stigmatization goes with cervical cancer. These women tend to withdraw."
He and his colleagues randomized 31 patients into one of two groups. One group received six counseling sessions by phone, with counselors discussing stress management, emotional and physical wellbeing, and sexual concerns. The other patient group received usual care.
All participants were tested for distress before and after counseling, and blood samples were taken at both times to examine telomeres.
"There was a trend toward individuals who got counseling to have a greater increase in telomere length compared with those who did not," Dr. Nelson said.
Genetic Protection Against Cancer
Also at the news briefing, Jian Gu, PhD, Assistant Professor of Epidemiology at the University of Texas MD Anderson Cancer Center, is delving into the connection between genetic influence on telomere length and cancer risk, research that was reported at the meeting but also simultaneously published in the AACR journal Cancer Prevention Research (2011;4;514).
Dr. Gu estimated that about 50% to 60% of the variation in telomere length is influenced by environment and lifestyle factors including diet, exercise, smoking, alcohol, air pollution, obesity, and psychological stress, with the rest related to genetics.
He and his coauthors analyzed 300,000 single-nucleotide polymorphisms (SNPs) from 459 healthy subjects, and found four SNPs to be significantly associated with telomere length and one, rs398652, that was linked to a 19% reduced risk for bladder cancer. About 15% of the population has the protective allele, Dr. Gu said.
"We confirmed that short telomeres conferred an indirect risk of bladder cancer."
Yet, he explained in an interview after the conference, telomere length is highly variable in individuals. "Telomeres can get longer. Fifteen to 20 percent of people have longer telomeres after 10 years."
It is as yet not known, however, if those longer telomeres prevent cancer or improve prognosis.
Asked for her opinion for this article, Paige McDonald, PhD, MPH, Chief of the NCI's Basic Biobehavioral and Psychological Sciences Branch, noted the need for more research: "We don't know cause and effect, and whether or not telomeres will be a target remains to be seen. The evidence is not overwhelming-larger-scale studies need to be done."
Dr. Nelson and others agree: "It will take much more time and additional studies to fully describe those interactions," he said.
His small study showed no effect of counseling or telomere lengthening on his subjects' cervical cancer. "The prognosis didn't change over that four-month period," he said."
Still, Dr. Blackburn urged clinicians to address patients' emotional needs: "Severe, prolonged psychological distress affects a substantial population, and it behooves us to have a more global approach to patients," she said.
"The ASCO Quality Oncology Practice Initiative [QOPI] includes distress and quality of life. I think that the science [of telomere changes] will bring that to a more prominent role. Taking care of the whole patient would have a true biological benefit."