Bright Lights, Big Cancer

A woman's blood provides better sustenance for breast cancer just after she's been exposed to bright light than when she's been in steady darkness, researchers led by David E. Blask of the Bassett Research Institute in Cooperstown, N.Y., report.

"Light at night is now clearly a risk factor for breast cancer," Blask says. "Breast tumors are awake during the day, and melatonin puts them to sleep at night." Add artificial light to the night environment, and "cancer cells become insomniacs," he says.

"Sleep per se is not important for melatonin," says Russel J. Reiter, a neuroendocrinologist at the University of Texas Health Science Center in San Antonio. "But darkness is."

The new study has far-reaching implications, says Reiter. First, it could spawn trials that test whether malignancies can be slowed down by altering a person's light environment or by using melatonin supplements. Second, he says, similar studies could show whether exposure to nocturnal light poses a prostate cancer risk to men, as some researchers suspect, or promotes other cancers previously linked to light at night.

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.

First, it could spawn trials that test whether malignancies can be slowed down by altering a person's light environment or by using melatonin supplements. Second, he says, similar studies could show whether exposure to nocturnal light poses a prostate cancer risk to men, as some researchers suspect, or promotes other cancers previously linked to light at night (SN: 8/28/04, p. 141: Available to subscribers at http://www.sciencenews.org/articles/20040828/note11.asp).

Occupational risk factors and male breast cancer

Martynowicz H, Medras M, Andrzejak R.

Katedra i Klinika Chorob Wewnetrznych, Zawodowych i Nadcisnienia Tetniczego AM we Wroclawiu. helenamar@poczta.onet.pl

Male breast cancer is rare compared to its female counterpart and makes less than 1% of all breast cancer. Its etiology is less known than that of female breast cancer. Numerous experimental and clinical studies indicate the possibility of an increased risk of male breast cancer in workers occupationally exposed to electromagnetic field, light at night, and high temperature. There are also studies, which reveal the increased risk of this disease induced by occupational exposure to pesticides, aromatic hydrocarbons and ionizing radiation. However, irrefutable epidemiologic data from prospective clinical trials have not yet been obtained.

PMID: 16483012

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16483012&query_hl=1&itool=pubmed_docsum

Urinary 6-sulfatoxymelatonin levels and their correlations with lifestyle factors and steroid hormone levels.

Schernhammer ES, Kroenke CH, Dowsett M, Folkerd E, Hankinson SE.

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Exposure to light at night, as experienced by rotating night shift workers, has been related to lower circulating levels of melatonin, a hormone with recognized cancer protective properties. However, little is known about the relationship of other lifestyle factors or endogenous sex steroid hormones with melatonin levels. We examined cross-sectional associations of age, reproductive and menopausal factors, body mass index (BMI), alcohol consumption, smoking history, night shift work, as well as several other breast cancer risk factors, and circulating sex steroid hormone levels with creatinine-adjusted morning urinary melatonin (6-sulfatoxymelatonin, aMT6s) levels. Participants were 459 healthy, primarily premenopausal (age range 33-50 yr) women from the Nurses' Health Study II (NHS II). Using multiple linear regression, we computed least-square mean hormone levels across categories of lifestyle factors. Age was inversely related to aMT6s levels, particularly before menopause (premenopausal women, </=39 yr versus >/=49 yr; aMT6s, 20.8 ng/mg versus 11.8 ng/mg creatinine; P for trend, 0.02). In multivariate analyses, BMI was significantly and inversely associated with aMT6s levels (P for trend, <0.01). Higher pack-years of smoking were associated with significantly lower aMT6s levels (never smoker versus 15+ pack-years, aMT6s = 17.4 ng/mg versus 12.3 ng/mg creatinine; P for trend, 0.04). We also observed a positive association between parity and aMT6s levels (P for trend, <0.01), but no other reproductive factors nor any of the sex hormones (estradiol, progesterone, estrone, estrone sulfate, dehydroepiandrostenedione, dehydroepiandrostenedione sulfate, testosterone, and androstenedione), as measured either in the luteal or the follicular phase of the menstrual cycle, were significantly associated with aMT6s. In conclusion, higher age, BMI, and heavy smoking were significantly related to lower levels of melatonin, whereas parity was significantly associated with higher aMT6s levels. Melatonin levels may be one mechanism through which these factors influence the development of cancer, but more studies are needed to elucidate these mechanisms definitively.

PMID: 16441548

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16441548&query_hl=1&itool=pubmed_docsum

Melatonin: what for?

Touitou Y.

Service de Biochimie Medicale et Biologie Moleculaire, Faculte de Medecine Pitie-Salpetriere, 91 boulevard de l'Hopital, 75013 Paris.

Melatonin (N-acetyl-5 methoxy-tryptamine) is a hormone secreted mainly by the pineal gland or epiphysis; it is also produced, but in much smaller quantities, by the retina. The key enzyme in melatonin synthesis is N-acetyl-transferase (NAT) whose activity increases during darkness. This explains why melatonin is mainly secreted at night. The circadian rhythm of melatonin synthesis is controlled by the suprachiasmatic nuclei--the "biologic clock". This clock itself functions rhythmically, being entrained by environmental synchronizers. According to the time of exposure, light has two effects on melatonin secretion, either suppressing or shifting its secretion (phase-response curve). Exposure to light in the morning advances the phase of the rhythm, while exposure in the evening delays it. Melatonin works in the opposite way, acting as a light signal transducer, and relaying information on the duration of day and night. Exogenous melatonin can synchronize some circadian rhythms, such as body core temperature. Current research is focusing on the properties of melatonin (and of light) as a resynchronizing agent in situations such as aging, blindness, shift work, night work, phase-advanced or phase-delayed sleep syndrome, and jet lag. Melatonin also has strong antioxidant properties (stronger than those of vitamin E), and an oncostatic action. Interestingly, three recent epidemiological studies show that women who work exclusively at night for long periods have a significantly elevated relative risk of breast cancer (RR 1.1-1.6). Other studies are required to confirm these results.

Publication Types:
· Review

PMID: 16433460

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16433460&query_hl=1&itool=pubmed_docsum

Night work and risk of breast cancer.

Schernhammer ES, Kroenke CH, Laden F, Hankinson SE.

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. eva.schernhammer@channing.harvard.edu

BACKGROUND: Melatonin shows potential oncostatic activity and is acutely suppressed by light exposure. Some evidence suggests an association between night work and breast cancer risk, possibly through the melatonin pathway. METHODS: In a cohort of premenopausal nurses, we prospectively studied the relation between rotating night shift work and breast cancer risk. Total number of months during which the nurses worked rotating night shifts was first assessed at baseline in 1989 and periodically updated thereafter. We used Cox proportional hazards models to calculate relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: Among 115,022 women without cancer at baseline, 1,352 developed invasive breast cancer during 12 years of follow up. Women who reported more than 20 years of rotating night shift work experienced an elevated relative risk of breast cancer compared with women who did not report any rotating night shift work (multivariate RR = 1.79; 95% CI = 1.06-3.01). There was no increase in risk associated with fewer years of rotating night work. CONCLUSION: Our results suggest a modestly elevated risk of breast cancer after longer periods of rotating night work. Additional studies are warranted to rule out small sample size or uncontrolled sources for confounding as alternative explanations.

PMID: 16357603
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16357603&query_hl=1&itool=pubmed_docsum

Melatonin-depleted blood from premenopausal women exposed to light at night stimulates growth of human breast cancer xenografts in nude rats.

Blask DE, Brainard GC, Dauchy RT, Hanifin JP, Davidson LK, Krause JA, Sauer LA, Rivera-Bermudez MA, Dubocovich ML, Jasser SA, Lynch DT, Rollag MD, Zalatan F.

Laboratory of Chrono-Neuroendocrine Oncology, Bassett Research Institute, The Mary Imogene Bassett Hospital, Cooperstown, New York 13326, USA. david.blask@bassett.org

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. Exposure of rats bearing rat hepatomas or human breast cancer xenografts to increasing intensities of white fluorescent light during each 12-hour dark phase (0-345 microW/cm2) resulted in a dose-dependent suppression of nocturnal melatonin blood levels and a stimulation of tumor growth and linoleic acid uptake/metabolism to the mitogenic molecule 13-hydroxyoctadecadienoic acid. 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 microW/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.

PMID: 16322268
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16322268&query_hl=1&itool=pubmed_docsum

Exposure to EMFs from any source that produces a field level of from 2 to 12 milliGauss can reduce melatonin production...........

Quoted here from the Journal of Pineal Research 14, "Incidence of selected cancers in Swedish railway workers, 1969-79" ; p89-97, March 1993

"These results provide the first evidence that ELF frequency magnetic fields can act at the cellular levels to enhance breast cancer cell proliferation by blocking melatonin's natural oncostatic action. In addition, there appears to be a dose threshold between 2 and 12 milliGauss. The mechanism(s) of action is unknown and may involve modulation of signal transduction events associated with melatonin's regulation of cell growth."

1: Biomed Pharmacother. 2005 Oct;59 Suppl 1:S24-30.

A multi-center four-hourly sampling of many tissues for 7 days (00:00 on April 5-20:00 to April 11, 2004), on rats standardized for 1 month in two rooms on antiphasic lighting regimens happened to start on the day after the second extremum of a moderate double magnetic storm gauged by the planetary geomagnetic Kp index (which at each extremum reached 6.3 international units) and by an equatorial index Dst falling to -112 and -81 nT, respectively, the latter on the first day of the sampling. Neuroendocrine chronomes (specifically circadian time structures) differed during magnetically affected and quiet days. The circadian melatonin rhythm had a lower MESOR and lower circadian amplitude and tended to advance in acrophase, while the MESOR and amplitude of the hypothalamic circadian melatonin rhythm were higher during the days with the storm. The circadian parameters of circulating corticosterone were more labile during the days including the storm than during the last three quiet days. Feedsidewards within the pineal-hypothalamic-adrenocortical network constitute a mechanism underlying physiological and probably also pathological associations of the brain and heart with magnetic storms. Investigators in many fields can gain from at least recording calendar dates in any publication so that freely available information on geomagnetic, solar and other physical environmental activity can be looked up. In planning studies and before starting, one may gain from consulting forecasts and the highly reliable nowcasts, respectively.

PMID: 16275503