Are female night owls screwed?

Posted by Tara C. Smith on January 16, 2006
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As I write this at 2AM sitting under annoying fluorescent lights, am I increasing my risk of developing breast cancer? Maybe, according to a recent study showing that melatonin-depleted blood can spur the growth of mammary tumors:

The increased breast cancer risk in female night shift workers has been postulated to result from the suppression of pineal melatonin production by exposure to light at night. Venous blood samples were collected from healthy, premenopausal female volunteers during either the daytime, nighttime, or nighttime following 90 minutes of ocular bright, white fluorescent light exposure at 580 µW/cm2 (i.e., 2,800 lx). Compared with tumors perfused with daytime-collected melatonin-deficient blood, human breast cancer xenografts and rat hepatomas perfused in situ, with nocturnal, physiologically melatonin-rich blood collected during the night, exhibited markedly suppressed proliferative activity and linoleic acid uptake/metabolism. Tumors perfused with melatonin-deficient blood collected following ocular exposure to light at night exhibited the daytime pattern of high tumor proliferative activity. These results are the first to show that the tumor growth response to exposure to light during darkness is intensity dependent and that the human nocturnal, circadian melatonin signal not only inhibits human breast cancer growth but that this effect is extinguished by short-term ocular exposure to bright, white light at night. These mechanistic studies are the first to provide a rational biological explanation for the increased breast cancer risk in female night shift workers.


While we know a good deal about factors that can contribute to breast cancer risk–including genetics (such as mutations in the BRCA1 and BRCA2 genes) and lifestyle choices (late or no childbearing, high fat diet, lack of exercise), many environmental risks for breast cancer remain controversial. Even the effect of cigarette smoking on breast cancer development remains uncertain, as does the environmental light idea. This new study, however, provides stronger evidence than previous epidemiologic studies that had linked the number of hours under artificial light to the development of breast cancer.

This isn’t a new hypothesis; indeed, it’s been bounced around for a few decades, and has been supported by a number of studies carried out in animals. At the heart of the connection are sleep cycles and the production of melatonin, which they discuss briefly in the article:

The duration of melatonin production during the night is directly proportional to the length of the dark period. The alternating light/dark cycle entrains circadian melatonin production to a 24-hour cycle, whereas ocular exposure to light during darkness rapidly suppresses melatonin production depending on the intensity, wavelength, and duration of the light exposure. In experimental systems, melatonin plays a fundamental role in the regulation of seasonal reproduction, circadian rhythm activity, retinal physiology, cardiovascular effects, immune function, and cancer.

Many tumors are dependent on a fat called linoleic acid in order to grow. Melatonin, however, interferes with the tumor’s ability to use linoleic acid as a growth signal, which causes tumor metabolism and growth activity to shut down. In figure 5 of their paper, the authors showed that tumor growth was repressed when tumors were “fed” melatonin-rich blood, while neither melatonin-poor blood collected either during the day or during the night following 90 minutes of exposure to white light had this effect. They also determined this was due to the action of melatonin by adding melatonin to the melatonin-poor blood, and blocking melatonin in the melatonin-rich blood. As expected, adding melatonin suppressed tumor growth, and blocking melatonin increased it, suggesting this is indeed an effect mediated by this chemical.

They conclude with possible ways to modify this potential risk factor:

Thus, strategies to preserve the integrity of the circadian melatonin signal (i.e., avoidance of bright light at night, intelligent lighting design, circadian-timed physiologic melatonin supplementation) coupled with modifications in nocturnal dietary fat intake may offer a unique approach to the prevention of breast cancer, and perhaps other melatonin-sensitive cancers, in our increasingly 24-hour society.

A problem with this is that currently, melatonin supplements aren’t regulated by the FDA, since they are dietary supplements and not officially “drugs.” If this connection is supported by further research, perhaps womens’ health advocates will need to make this a priority. While I simply prefer to work at night (I’ve always been more productive after everyone else is asleep), many women don’t have the luxury of choosing their shift–and their health shouldn’t suffer because of it.

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Comments

  1. #1 M. L. Green
    January 16, 2006

    Let us hope not.

  2. #2 Apesnake
    January 16, 2006

    While this is an interesting study and a great topic for a science blog, I just know that the media will report this as “New study proves that light at night causes cancer”.

    Medical studies (especially ones that have novel findings) tend to be given far more weight then they should in the popular press. So much effort has been made to impress upon the media the importance of peer review in the scientific process (due to the creationist battles and other pseudo-science attacks) that the distinction between peer review for publication verses wider peer review for validation is often lost on those who are not familiar with academic publishing.

    Still, it is interesting that a possible mechanism has been suggested for this phenomenon (one I had not heard about).

  3. #3 Apesnake
    January 16, 2006

    Also, it would be interesting to compare results of shift workers who are naturally “night-owls” with those who do shift work because they have to. Or those who have done shift work for a long time verses those who have just started.

  4. #4 Tara
    January 16, 2006

    The media stories I saw about it were a bit more reserved. The headline for this one is almost on-target for what you predicted, but they temper the discussion with a lot of uncertainty.

    As far as the other studies you mention, I agree they’d be nice. Indeed, they might have already been done, at least as far as measuring melatonin levels in the populations you suggest. I took a very brief jaunt through the melatonin lit, and there’s more out there than I realized.

  5. #5 Apesnake
    January 16, 2006

    I suppose there is a strong incentive for researchers to look at melatonin because it is available over the counter and is being recommended in alternative health circles. I am sure that many people would be wondering about its effects. Given that it is a human hormone I am surprised that it is not known to produce any toxic side effects especially seeing that people are using it in an unregulated fashion.

  6. #6 coturnix
    January 16, 2006

    This is an excellent study by some of the top researchers in the field (M.Dubocovich is the top melatonin researcher, and Rollag designed the first – and still the most reliable – melatonin RIA, which I have used).

    My family is asking the breadwinner (me) to get some food RIGHT NOW, but I’ll be back. If it gets too long I may write it on my blog and link back to you.

  7. #7 coturnix
    January 23, 2006

    Trackback in a manner of speaking….

  8. #8 impatientpatient
    January 24, 2006

    http://jncicancerspectrum.oxfordjournals.org/cgi/content/full/jnci;94/7/532

    Hopefully this link works. In it is response to an argument that increased domestic stress on women shift workers raises cortisol levels, and may affect pineal functioning. To which it is replied that that may be partially true but melatonin levels really ARE affected by light at night and melatonin levels affect cancer rates for real.

    Why did I put that in there- because I am so tired of psychological stress being perceived as THE cause of disease in women. Women have enough to worry about when it comes to getting breast cancer and “too much stress that could have been controlled” is a stupid thing to blame. There seem to be a lot of doctors that want to blame stress (and therefore their patients lack of control over it) for everything, rather than look and see if there are other or inter-related causal factors.

    Dr. Shernhammer at the Channing Laboratory studied med records of 78562 nurses and reviewed 13 other studies. The numbers indicated a 36-48 percent increase in breast cancer in nurses who worked the night shift 30+ years.
    Melatonin receptors are located throughout the body, and it causes cell division to slow. It counteracts estrogens tendency to speed up cell growth, is what Steven Hill PHD at Tulane University proposes.

    Blind women have a 50 percent LESS risk of cancer according to four different studies since 1991.

    Blask and Brainard infused human breast cancer tumours with blood from healthy premenopausal women. Samples were taken throughout the day, and the samples taken at night when melatonin production was highest slowed tumour growth by 80 percent comparatively.

    No-one is willing to make the causal connection however, because there are uncertainties as to how things interact with each other……..

    This is a very short synopsis of an article in Prevention Magazine- January 2006. I think I wrote it correctly. But if you choose to you can google on and read what is available on line.

    Could proper Omega 369 balance and melatonin supplements help shift workers? What are the risks for men who work nights?

  9. #9 Tara
    January 25, 2006

    impatient,

    I agree re: stress. I’ve said before that’s a catch-all explanation. We need to tease that out a lot more to figure out what the real physiological factors are when “stress” is attributed as a cause or co-factor.

    Re: Omega 369 and melatonin, I’m not familiar with the former. As for the latter, maybe. Check out coturnix’s post linked above for a more thorough fleshing out of the melatonin issues.

    Re: men, I was wondering that myself (my dad worked 3rd shift for many years) and couldn’t find much. Some conflicting studies but nothing conclusive.

  10. #10 impatientpatient
    January 25, 2006

    http://www.biochem.northwestern.edu/holmgren/Glossary/Definitions/Def-L/linoleic_acid.html

    Omega 3 is in fatty fish and flax, Omega 6 is another word for linoleic acid and omega 9 is oleic acid.

    They are the Essential fatty acids. The reason I asked if the three omegas should be balanced properly is because there is a school of thought that says that we do not get enough Omega 3′s and we have to much 6 and 9 in our diets, and that contributes to ill health.

    Eat more fish and flax and health will be better overall.

    You wrote:

    Many tumors are dependent on a fat called linoleic acid in order to grow. Melatonin, however, interferes with the tumor’s ability to use linoleic acid as a growth signal, which causes tumor metabolism and growth activity to shut down.

    ….which is why I made the leap to Omega threes being balanced. If we are ingesting too much linoleic acid then what can be done.

    Thank you for your agreement about stress…I could, but won’t, tell you horror stories about bad medicine that ignores the body and searches the psyche……… More than a pet peeve of mine these days.

  11. #11 Tara
    January 26, 2006

    Ah, okay. I’m familiar with them individually but wasn’t thinking about 3-6-9 as a shorthand term for them all. Sorry, dumb moment on my part. A reasonable hypothesis…don’t know how much work has been done on it in the cancer field.

  12. #12 impatientpatient
    January 28, 2006

    http://jama.ama-assn.org/cgi/content/short/295/4/403

    Well, the work here is compiling a bunch of heterogenous studies and what it looks like is there doesn’t seem to be an effect.

    Would this be a meta-analysis?

    Are these kinds of studies of studies really effective?

    Are self reporting studies accurate- let’s say that I self report that I ate these foods in a month. Are portions and amounts going to be correct. I was talking to a professor in dairy cow research, and she was saying that because you can actually control what animals eat for research purposes, it is easier and more accurate to do animal nutrition studies.

    How do you do a good nutrition study in people?

  13. #13 Tara
    January 29, 2006

    Yes, that could be considered a meta-analysis, although using “unpublished literature sought through letters to experts in the neutraceutical industry” biases it somewhat…what about the unpublished lit elsewhere?

    As far as nutrition studies, they aren’t easy. There’s a prof in my department who works in that field, and they use questionnaires that have been validated–they’ve compared what people actually ate (by observation) with what they reported, so that the error rate can be estimated. In their analysis, I glanced quickly and didn’t see that referred to–did all the studies use the same questionnaire? I’d take their findings with a grain of salt.

  14. #14 impatientpatient
    January 29, 2006

    I have another question- what does it mean in a study that disagreements are solved by consensus? THAT has shades of that Jesus seminar thing attached to it. I honestly thought that science is not based on consensus which can be flawed by a number of factors including personality, but was based on empirical evidence. (correct word?) I have seen a lot of metaanalysis studies that seem to use the same way of doing business, and I have always wondered how that works. I am such a layperson, but am totally curious.

    TO me, if consensus is built into science as any factor at all, then it means that bias can enter in. If no-one wants a certain thing to be so, then they can, by consensus, make it go away.

    Am I right to be skeptical? Or do I read too much into these things?

  15. #15 impatient patient
    February 21, 2006

    Tara

    I believe it is at Orac’s site -which I just quickly glanced through but didn’t find- because I really wanted to not forget this-

    On his site was a reference to a flax seed muffin study that found I think a positive correlation between eating the muffins and lower cancer incidences. That is the non-scientist version. But it goes with my Omega 3 thing, as flax is a source of Omega 3′s . 2 studies actually- one from Canada.

    Also- what do glia have to do with what you study? They are immunocompetent- microglia and astrocytes anyways- and I wonder if there is a tie-in to what you do in your science.

    Hope your long weekend was wonderful.