The short-term goal of the workshop was to lay the foundation for the development of a better understanding of the extent to which changes in the lighted environment that come with industrialization contribute to the etiology and affect the risk of human disorders such as breast cancer, other cancers, and other chronic diseases. Another workshop objective was to foster an understanding of the role that light plays in conjunction with other environmental and endogenous factors (e.g., fatty acids) that may affect cancer development and growth. Of primary concern are the altered light exposures during the night and day as they impact circadian and diurnal physiologic rhythms. It is also a priority to understand the biological mechanisms connecting disruption of circadian and diurnal processes with disease etiology. Importantly, characteristics of the individual that might modify the effect of environmental lighting on health need to be elucidated. The long-term goal is, of course, to use the newly acquired knowledge of the mechanisms and consequences of circadian disruption from altered lighting to develop interventional strategies and technologies for reducing health risks from, for example, non-day shift work in which a large and increasing segment of the population is employed.
There are three broad areas of research effort that need to be addressed. First are the basic biophysical and molecular genetic questions of how the retina transduces the photic input to a neuronal signal to the circadian system and other brain neural substrates that mediate non-image-forming effects of light, and once received, how these signals are transduced to other cells and tissues of the body. It has become clear that photic sensing for the circadian, neuroendocrine, and neurobehavioral effects of light is not by vision per se but via a novel photoreceptor system located in the ganglion cell layer of the retina. Fundamentally, the basic biophysics of nonvisual phototransduction needs to be understood, that is, its absolute, spectral, spatial, and temporal response characteristics. Among the interesting questions identified: Do the absolute and spectral sensitivities change throughout the solar day? Does a single spectral sensitivity characterize the photic input to every light-responsive, nonvisual system of the brain? How does prior light exposure affect light sensitivity (Hebert et al. 2002
)? And, significantly, how can basic knowledge be used to develop lighting regimens or sources that mitigate the adverse consequences of altered light exposure, for example to reduce circadian misalignment in shift workers?
Second are questions of physiologic consequences of disrupting the normal functioning and temporal synchronization of the circadian and other neurobehavioral systems: How are hormone production and release affected both acutely and chronically? How are the timing and synchronization of metabolic processes affected? How does altering clock gene function affect cell cycle checkpoint genes and genes of apoptosis in susceptible tissue such as breast and prostate? These questions can be addressed in laboratory studies in experimental models and in clinical trials with human subjects with end points such as circulating hormone level alterations over the course of a 24-hr period.
shows an integrative model for a light-induced effect on breast cancer etiology [adapted from Stevens (2005)
]. Specific genetic polymorphisms may act at several points along this proposed causal pathway. There has been one study published based on this scheme that reported increased risk of breast cancer in young women with a polymorphism in one of the clock genes, Per3
(Zhu et al. 2005
Figure 3 Model for mechanisms for a light-induced effect on breast cancer [adapted from Stevens (2005)]. Possible targets for research on genetic polymorphisms that might affect the process are indicated.
Third are questions of disease occurrence, prevention, and treatment, which must be addressed with epidemiology and clinical trials. For example, can risks for specific diseases such as breast cancer be quantified in terms of light exposure, and can this information be used to mitigate exposure and lower risk?
Twenty-five attendees of the NIEHS workshop identified five core areas of priority research effort. These are all closely intertwined with one another and directed toward the larger goal of understanding how light and dark influence human health in the modern world. Each core area requires expertise from different but overlapping scientific disciplines, and cross-disciplinary communication among researchers in the five areas is paramount.