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Light, endocrine systems and cancer - facts and research perspectives. Proceedings and abstracts of the Cologne Light Symposium 2002. May 2-3. 2002. Cologne, Germany. Neuro Endocrinol Lett. 2002 Jul; 23(Suppl 2): 4-104
: Research on light at night and cancer is evolving at an accelerating pace, fueled largely by exciting results in rodent toxicology and basic human biology. Epidemiologic research is at a relatively early stage of development in which the exposure surrogates such as shift work and blindness predominate. Causal graphs for shift work, light at night and breast cancer illustrate some of the subtleties that can arise in the use of exposure surrogates of different kinds. Baseline data on circadian rhythms and melatonin cycles among human populations living at different latitudes are needed. Epidemiologic study of this topic is expected to mature soon as studies begin to incorporate quantitative and semiquantitative measurements and personal histories of exposure to light at night. The current emphasis on breast cancer should widen to include other cancers and intermediate outcomes. An advance in epidemiologic studies of blind persons would be to compare cancer rates between the "cortically blind" and the "retinally blind" within levels of visual impairment. Without a proposed intervention to reduce exposure to light at night, attributable fraction and attributable caseload estimates are meaningless. In the near future, both epidemiologic and laboratory research in this area are expected to grow appreciably in scope and scale....
Poole C. The darkness at the end of the tunnel: summary and evaluation of an international symposium on light, endocrine systems and cancer. Neuro Endocrinol Lett. 2002 Jul; 23(Suppl 2): 71-78
: Visible light of sufficient intensity and duration inhibits melatonin biosynthesis, and experimental studies suggest that melatonin may protect against cancer. From a public health point of view it is important to verify or falsify the hypothesis that artificial light--or even sunlight itself--suppresses melatonin production sufficiently to increase the risk of developing cancers of internal organs in man. Epidemiology is a discipline that can contribute to in-vivo verification of experimental findings. But when attempting to study the effects of light on man, epidemiologists are faced with a major problem: the ubiquitous nature of natural and anthropogenic light, which renders everyone, everywhere exposed. The challenge is to identify populations with demonstrable varying exposures to light. This paper summarizes how recent epidemiological investigations have sought to tackle the problem by studying shift-workers, blind people and Arctic residents. It is suggested that future studies should test the underlying assumptions regarding endocrine responses to light, i.e., that melatonin levels are reduced among shift-workers, and that they are increased among the blind and those who live in the Arctic. A systematic investigation of exposure-response relationships could be based on "light dosimetry by geography". Such a study is envisaged by European researchers who aim to study melatonin and other hormones in samples from healthy general populations that are differentially exposed to light by virtue of varying ambient photoperiods. Further methodologic options for prospective and retrospective epidemiologic studies are suggested. It is concluded that the biologically plausible link between ubiquitous light, hormones and the development of very frequent malignancies such as breast cancer and prostate cancer should be investigated rigorously by additional well-designed epidemiological research....
Erren T. Does light cause internal cancers? The problem and challenge of an ubiquitous exposure. Neuro Endocrinol Lett. 2002 Jul; 23(Suppl 2): 61-70
: Risk of breast cancer varies by about 5-fold among societies, and incidence and mortality have been increasing worldwide for many decades. Migrants from low-risk Asian societies to the U.S. suffer elevated risk of breast cancer in their own lifetimes, and the second or third generation Asian-Americans attain the high risk of the multi-generational European immigrants [1,2]. Something about a modern Western lifestyle apparently increases risk dramatically. Madigan et al. [3] estimate that 41% of the new U.S. cases of breast cancer are explained by "known risk factors"; these include the reproductive factors of age at first birth, menarche, menopause. They ascribe about 30% to reproductive factors when they are analyzed alone. "High income" is estimated to account for about 19% when analyzed by itself. The 41% is an analysis taking all the factors together, and since they are related, the total is less than the sum of estimates for the individual items. By itself, "High income" has no biological interpretation and must reflect attributes of lifestyle and/or environment that increase risk. So, the proportion of breast cancer cases in the U.S. that can be accounted for by known biological risk factors is about one third. Therefore, at least half of breast cancer risk in the U.S., and other Westernized/industrialized societies, is in excess of that found in non-industrialized societies and is without any agreed-upon explanation. Many candidate factors exist, each with a cadre of proponents. The sum of these may turn out to explain the bulk of the excess risk in modern societies. On the other hand, they may not, and worse, may fall woefully short....
Stevens R. Lighting during the day and night: possible impact on risk of breast cancer. Neuro Endocrinol Lett. 2002 Jul; 23(Suppl 2): 57-60
: Over the past few years, we have shown that the surge of melatonin in the circulation during darkness represents a potent oncostatic signal to tissue-isolated rat hepatoma 7288CTC, which is an ER+ adenocarcinoma of the liver. This oncostatic effect occurs via a melatonin receptor-mediated suppression of tumor cAMP production that leads to a suppression of the tumor uptake of linoleic acid (LA), an essential fatty acid with substantial oncogenic properties. The ability of LA to promote cancer progression is accomplished by its intracellular metabolism to 13-hydroxyoctadecadienoic acid (13-HODE) which amplifies the activity of the epidermal growth factor receptor/mitogen-activated protein kinase pathway leading to cell proliferation. By blocking tumor LA uptake, melatonin effectively blocks the production of 13-HODE and thus, markedly attenuates tumor growth. A similar effect of melatonin is observed in tissue-isolated, ER+ MCF-7 human breast cancer xenografts and nitrosomethylurea (NMU)-induced rat mammary cancers. When male rats bearing tissue-isolated hepatomas are exposed either to constant bright light (300 lux) or dim light (0.25 lux) during the dark phase of a 12L:12D photoperiod, the latency to onset was significantly reduced while the growth of tumors was markedly increased over a 4 wk period as compared with control tumors in 12L:12D-exposed rats. In constant light- and dim light during darkness-exposed rats, melatonin levels were completely suppressed while tumor growth, LA uptake and 13-HODE production were markedly increased. Similar results were obtained in constant bright light-exposed female rats bearing tissue-isolated NMU-induced mammary cancers or MCF-7 human breast cancer xenografts. To date, these studies provide the most definitive experimental evidence that light exposure during darkness increases the risk of cancer progression via elimination of the nocturnal melatonin signal and its suppression of tumor LA uptake and metabolism to 13-HODE....
Blask D, Dauchy R, Sauer L, Krause J, Brainard G. Light during darkness, melatonin suppression and cancer progression. Neuro Endocrinol Lett. 2002 Jul; 23(Suppl 2): 52-56
: The skin is the most common site of malignancy. Due to several mostly unknown factors, the frequency of skin tumors is increasing. Except for malignant melanoma, reliable statistical data on the frequency of skin tumors are scarce. Discussion on the epidemiology of skin tumors may take different aspects and factors into consideration: (1) histogenetic type; (2) race, (3) sex; (4) age, (5) localization; (6) environment. Moreover, precancerous conditions also may play an important role in this context. Epithelial tumors, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most frequent tumors of the skin. Figures show a wide range between 40 and over 700 or 5 and 250 respectively per 100 000 inhabitants per year depending on the country or area of report. Malignant melanoma is more frequently seen in Caucasians living in sunny regions (40) than in northern countries or in dark skinned races (4-12 per 100 000 per year), representing 4% of all skin tumors, but being responsible for 79% of skin cancer deaths. Other types of skin tumors like cutaneous lymphoma, Kaposi sarcoma, lipomas, adnexal tumors etc. are either not reported regularly and reliable epidemiologic data is not available, or are rare cutaneous tumors (taken all together < 1%)....
Böni R, Schuster C, Nehrhoff B, Burg G. Epidemiology of skin cancer. Neuro Endocrinol Lett. 2002 Jul; 23(Suppl 2): 48-51
: Endocrine modulation by natural and synthetic chemicals and the eventually resulting beneficial or adverse effects for human and animal health are controversially debated not only among scientists but particularly in the public. Most information is available on so-called environmental estrogens, however the amount of information on substances interfering with other hormonal axes steadily increases, particularly on those exhibiting (anti)androgenic activities. The aim of this paper is to summarize existing data and to give an overview on the potential pathways leading to interferences of environmental hormones with homeostasis and eventually resulting health effects. Experimental evidence suggests the hypothesis that fetal and neonatal organisms may be at risk if exposed to environmental estrogens. In contrary, it appears as if phytoestrogens, particularly those with selective estrogen receptor modulator- (SERM-)like activities have the potential to be useful in medical application, both as dietary means and as pharmaceuticals. Lacking valid information about the detailed analysis of the molecular mode of action for environmental estrogens, the possibility for an ultimate classification of environmental estrogens in "dangerous endocrine disruptors" and phytoestrogens in "useful pharmaceuticals" cannot be supported conclusively. Nevertheless both activities are likely....
Vollmer G, Starcke S, Wober J, Zierau O. Endocrine modulation and the fragile balance of homeostasis--an overview. Neuro Endocrinol Lett. 2002 Jul; 23(Suppl 2): 37-42
: The role of the modulation of the pineal gland function in development of cancer is discussed in the review. An inhibition of the pineal function with pinealectomy or with the exposure to the constant light regimen stimulates mammary carcinogenesis, whereas the light deprivation inhibits the carcinogenesis. Epidemiological observations on increased risk of breast cancer in night shift workers, flight attendants, radio and telegraph operators and on decreased risk in blind women are in accordance with the results of experiments in rodents. Treatment with pineal indole hormone melatonin inhibits carcinogenesis in pinealectomized rats or animals kept at the standard light/dark regimen (LD) or at the constant illumination (LL) regimen....
Anisimov V. The light-dark regimen and cancer development. Neuro Endocrinol Lett. 2002 Jul; 23(Suppl 2): 28-36