AACR 102nd Annual Meeting, 2—6 April 2011, Orlando, Florida

Chronic stress of cancer causes accelerated telomere shortening

Dr Edward Nelson – University of California, Irvine, USA

The different genetic and chromosomal influences on health now coming out of this American Association for Cancer Research meeting here in Orlando. Edward Nelson, you have been looking at chromosomes, you’ve been looking at telomeres and you’ve been looking at psychological aspects, stress for example. First of all, why were you interested in stress and cancer and telomeres, and how do they all fit together?

We’ve been interested in the role of chronic stress and the biological consequences thereof and how that influences both our cancer patients’ capacity to handle their disease and how improvement in quality of life, improvement of their capacity to handle the intrinsic stresses of having cancer and being treated for cancer, how we might modulate that in a way to improve outcomes of our patients.

Now, how do you define stress, and why did you think it’s really important for doctors to start to think in terms of stress and their cancer patients?

Well I think there are some populations, for example the population that we study which are cervical cancer patients, who it is well known that they are profoundly disruptive in their quality of life. The disease itself and the treatment create a multitude of physiologic problems, it has issues of reproduction, there is a social stigmatisation and social disengagement by these women, and so they are dramatically affected in terms of their quality of life. So when one thinks about the overall care of a patient, it’s not just doing your surgery, radiation and chemotherapy but it is also trying to allow these women, and our patients as a whole, to live good quality lives for the remainder after their treatment. So we’ve been interested not just in how to make that happen but also what is the mechanism by which that might manifest itself in an improved clinical outcome.

And you’ve got an important factor here because you are looking at telomeres. Can you remind me what exactly they are in relation to the chromosome and why they might be important?

So telomeres are the protective caps to chromosomes. Dr Blackburn refers to them as the applets on the shoestring, but they fundamentally keep the chromosomes from fusing together or from rearranging, and if they are too short you get a chromosomal crisis; that crisis can lead then either to the cell committing suicide or to a transformative event which then goes on to, of course, develop cancer or have the potential to develop cancer. So in general longer telomeres are better; if they get too short that’s a bad thing, and so on.

And you were measuring these in your cervical cancer patients?

So we were measuring the telomere length in peripheral blood mononuclear cells in cervical cancer survivors, yes.

What did you find?

Our study was, if you will, a retrospective study of a randomised trial where we had a psychosocial counselling intervention for the cervical cancer survivors. Where we had already demonstrated that the intervention could improve their quality of life and could modulate stress associated biomarkers, amongst those were a change in immunological stance. So under chronic stress conditions individuals have a shift in their immunological stance to a more TH2 prominent immune stance. And so we hypothesise that if we improved their stress response and their quality of life that then that shift might come back a little bit and we would see a more prominent TH1 component; and in fact that’s what we saw in the initial study. We then became aware of the work of Dr Zappel and Blackburn that showed there was an accelerated shortening of telomeres in individuals who were chronically stressed, and these were in non-cancer patients. So our question then was we have a population where we think we have modulated their stress response by modulating the biomarkers, would we also then modulate the telomere, the accelerated telomere shortening that had been described for other chronically stressed populations.

And did it?

It did. So in those individuals who had decreasing levels of psychological distress, they had an increase in their telomere length. That was predominantly from the CD3 positive T cell component, it was associated with a shift in the TH1 component and prominence of the immunological stance, and so it sort of ties together nicely with our other studies.

It does all tie together very nicely. This was, of course, a small group.

Absolutely.

Of 31 women, is that right?

31 women and we utilised a methodology called FLO-FISH for measuring telomeres and that gives us a relative telomere length, but it is a flow cytometry technology and methodology and so there is variability. So in our hands the coefficient of variation was 10%, so we only analysed for these associations individuals who had a longitudinal change greater than plus or minus 10%.

So you were getting a big effect, a small number of patients.

Yes.

It is indeed hypothesis generating.

Yes, very much so.

What hypothesis do you come up with? What kind of guidelines might come out of this if this is justified with bigger studies?

So there is a body of literature for both chronic stress and for shortened telomeres as having prognostic factors for chronic diseases such as cardiovascular disease, even some pulmonary diseases and some GI entities. So it’s tempting to hypothesise that if we can handle or improve the way that our patients and prospective patients handle their stress response that this may have biological consequences that would allow them to perhaps handle the genetic and other insults somewhat better, at least at the immunological standpoint.

Of course stress is a difficult thing to measure and not everybody agrees about what stress is.

That’s true.

Can I pick your brains about what, in your view, are the stresses to be avoided and how to avoid them, say in a practical clinical medical situation?

So for our study we attributed the stresses to the diagnosis and to the treatment and viewed it as a chronic stress. My biological colleagues think of stress in terms of reactive oxygen species that cause problems inside a cell. Our students think of stress as their more rapid heartbeat when they step into an exam room, but this chronic psychological stress we all sort of think we know what that means and it is very difficult to quantify. The measure that we used was a measure of psychological distress, so we were actually measuring decrease in distress as, if you will, a surrogate for an improvement in the stress response. It’s important to recognise that by and large we don’t remove the stressors, we don’t take away the diagnosis and we don’t change the socio-economic status.

But you can learn better how to cope with it?

But you can learn better how to cope with it, exactly. And perhaps that is the major take home message, is that if, as practising clinicians, we can help our patients to cope with whatever the stressors are that we can be assured that there are downstream biological consequences of doing that which are beneficial to the patient, and whether that translates into better outcomes will remain for much larger and longer studies, but that would be the hypothesis.

That seems to be a very, very helpful message. Have you got any tips, just very briefly, on how to do it?

Well not out of our work, but others have looked at such simple things as exercise where, and we all know exercise is better for us but it is also a stress reliever, and in individuals for whom they are not sedentary but actually exercise they have a greater degree of increase in their telomere length if their stress levels go down. So we should all exercise more.

So exercise and maybe many other factors too.

That’s correct.

Edward Nelson, it’s great to talk with you. That is really interesting and we hope to hear more about your fascinating work. Thank you for joining us on ecancer.tv.

You are very welcome, thank you.