Telomeres and Cancer Prevention
Elizabeth Blackburn from UCSF spoke to us on “A New Paradigm for Cancer Prevention: What We Are Learning from Chromosome Ends”. Dr. Blackburn is a Nobel Prize winner for her study of telomeres.
According to the American Cancer Society, 44% of men and 38% of women will develop cancer in their lifetimes. Of these, 84% are diagnosed after the age of 60. The objectives of current oncology medicine are to:
- Diagnose and treat cancer before it becomes symptomatic.
- Gain an understanding of the disease from a molecular/genetic perspective.
- Improve the efficacy of the treatments and lower the cost of illness.
If these broad objectives are realized, they would lead to, on the one hand, prevention of the disease, or, if not caught before tumor growth, an understanding of the dynamics of the disease, which would lead to less toxic and more effective therapies.
If we think of cancer progressing from a pre-malignant state to an advanced stage, there are many opportunities to intervene. What Dr. Blackburn calls tertiary prevention is medical intervention to control the symptoms and morbidity of the cancer itself and the toxicity of cancer therapy. This is being done now, but if we go further back to secondary prevention, we’re talking about early detection of pre-malignant cells and intervention to stop progression. Examples of this are removing polyps during a colonoscopy to prevent colo-rectal cancer and prophylactic mastectomy in women who have the BRCA mutation to prevent breast cancer development. A third example is the removal of pre-cancerous cells in the cervix that are detected by a PAP smear. A future possibility is the removal of intraductal carcinoma in situ, or pre-malignant breast disease that is known to develop into malignant breast cancer if left alone. Another future example is to use immunotherapy and possibly vaccines to intercept the cancer in an early stage. Primary prevention is to intervene before the cancer has even developed, like with the HPV (human papillomavirus) vaccine to prevent cervical cancer. There are also actions that can be taken to avoid getting cancer in the first place. Not smoking is obvious, but there are also indications that dietary changes, exercise, and avoiding exposure to environmental carcinogens and psychosocial stress can stop cancer before it starts.
Dr. Blackburn then got into the part of her talk that dealt with telomeres, the study of which won her the Nobel Prize. Telomeres are little pieces that cap the two ends of chromosomes. She made the analogy of the telomere to the aglet on a shoelace. If it falls off, the shoelace becomes frayed and dysfunctional. That’s what happens when the telomeres wear off.
When cells divide, their DNA is replicated. The process is not 100% perfect, so after a while, part of the ends of the chromosomes are lost – see below. These end pieces, capped with protective proteins, are called telomeres. By old age, much of the telomeres are lost leaving the DNA unprotected against change.
The telomeres are replenished by an enzyme called telomerase. If one does not have enough telomerase, then the telomeres become depleted leading to what is called senescence, or inability of the cells to renew themselves.
So what does this mean to us? There have been several studies that link diseases to shorter telomeres: cancer, cardiovascular disease, vascular dementia, diabetes, osteoporosis, etc. On the other hand, a large study associated years of healthy life with longer telomere length. So, what can we do about it. Note that telomeres can get longer as well. Influences on telomere length are both genetic and environmental.
A study has shown that the more years a caregiving mother has been under chronic stress, the shorter are her PBMC telomeres, where PBMCs are peripheral circulating mononuclear cells or white blood cells like lymphocytes, which fight infection. Another study associated the chronic stress of women caregivers of dementia patients (like their husbands) with shorter PMBC telomere length. Other studies have correlated degree of pessimism, as reported on questionnaires, with shorter telomere length. These studies don’t bode well for a pessimistic mother of a troubled child who also cares for a parent with dementia. Also check out President Obama’s hair, greyer than when he took office – is it the stress of the job?
What factors affect telomere length in a positive direction? A study of stable cardiovascular patients correlated omega-3 fatty acid blood levels with loss of telomere length over a 5-year period and found that the higher the omega-3 level, the lower the loss in length. In fact, there was a strong association between increase in leukocyte telomere length and high serum omega-3 levels. These were retrospective studies, so Dr. Blackburn is doing a prospective, placebo-controlled study to verify the results. The lesson learned is eat fish, or at least take fish oil pills.
Dr. Blackburn is currently studying men who have been diagnosed with prostate cancer at an early stage and are under “watchful waiting” to see if a program of exercise and diet can affect prognosis. In very early results, she found that an increase in telomerase activity was associated with an increase in LDL (good) cholesterol levels. Another study tracked a group of people who did intensive meditation and their psychological well-being indicators. One thing it found was that their “purpose-in-life” correlated with increased telomerase activity.
Finally, in the study of women under chronic stress, who experienced shorter telomere lengths, researchers found that the women who exercised more had less of a loss of telomeres. So the exercise alleviated the stress. There are a number of studies being conducted at UCSF and other institutions relating telomere length and telomerase levels to psychosocial parameters.