CORRESPONDENCE


 

RESPONSE: Re: Night Shift Work, Light at Night, and Risk of Breast Cancer

Scott Davis, Dana Mirick, Richard Stevens

Affiliations of authors: S. Davis, Ph.D., Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center and Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle; D. K. Mirick, Program in Epidemiology, Fred Hutchinson Cancer Research Center; R. G. Stevens, Department of Community Medicine, University of Connecticut Health Center, Farmington.

Correspondence to: Scott Davis, Ph.D., Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. North MP-474, P.O. Box 19024, Seattle, WA 98109–1024 (e-mail: sdavis{at}fhcrc.org).

Drs. Spiegel and Sephton rightly point out that the association we reported (1) between being employed in graveyard shift work and an increased risk of breast cancer might be accounted for by mechanisms other than or in addition to suppression of the normal nocturnal rise in melatonin, and they suggest that loss of diurnal variation in cortisol levels might be one such alternative. Women who engage in night shift work are subject to the influence of both sleep disruption and exposure to light-at-night (LAN). Sleep deprivation can have a profound effect on endocrine function and hormones such as melatonin and cortisol (2), and it is well established that exposure to LAN can affect pineal function and the production of melatonin (3). Spiegel and Sephton cite recent evidence (4) of a similar effect on cortisol. In addition to the prognostic significance of altered cortisol patterns that they describe, there is beginning to emerge some limited evidence (5,6) that cortisol may be associated with the risk of developing breast cancer as well.

If breast cancer risk is affected by the suppression of the normal nocturnal rise in melatonin, one would predict that 1) persons who do not perceive light on the retina (e.g., those who are blind) would be at a decreased risk of breast cancer and 2) those who work in occupations that are characterized by circadian disruption (e.g., flight attendants) and those who work the graveyard shift in whatever occupation would be at an increased risk of developing the disease. Our results, as well as those from a number of other studies, are consistent with these predictions, but they could also be consistent with other mechanisms. Indeed, Funk and Amir (7) have raised the intriguing possibility that factors such as stress and fear may modify the effect of light on hormone production. Epidemiologic studies cannot distinguish with much certainty which underlying biologic mechanisms account for or can best explain associations observed on a population basis. However, they can inform the design of laboratory-based investigations that are capable of identifying specific mechanisms.

Dr. Porock and Mr. Gentry also point out that a number of different factors may be important in the development of breast cancer and express concern that our results are derived from self-reported data obtained through an in-person interview. The limitations of this approach are well recognized, and we used several techniques (e.g., structured interview, pilot tests, extensive interviewer training and monitoring, and a random sample of abbreviated re-interviews) to help ensure that the data were collected in an unbiased manner and were as accurate as possible. The potential impacts of imperfect or biased recall were considered in our original paper (1). Porock and Gentry are also concerned that our primary findings are based on a small difference in graveyard shift work between cases and controls and that a simple statistical test of the difference is not significant. Although a relatively small number of study participants worked the graveyard shift, the more relevant comparison is that a considerably higher proportion of those who did work the graveyard shift were cases (60%) than were controls (40%). These and similar statistically significant results summarized in Table 3 of our original paper (1) are more informative and also allow for the independent effects of other factors related to breast cancer risk when evaluating the effect of graveyard shift work. We concur that the potential importance of our findings dictates that future research be thoughtfully designed and carefully executed, and we hope that our results help direct the design of the next generation of epidemiologic and laboratory studies.

We appreciate the thoughtful comments of Dr. Kerenyi and encourage him to more fully describe and publish his findings regarding workers who spend much of their time in darkness. We have also had a long-standing interest in the etiologic role of exposure to LAN in the development of cancer (8) and agree that accumulating evidence warrants further study of the potential effects of such exposure. We currently have a proposal under review to initiate a study to measure melatonin and reproductive hormone levels in women who work at night and in women who work during the day. The results of such a study may be useful in designing a trial of the potential beneficial effect of melatonin replacement by providing information on hormone patterns associated with different work and sleep schedules. We agree that such approaches may lead to a better understanding of the health impacts of exposure to LAN and the resulting disruption of normal circadian biology.

REFERENCES

1 Davis S, Mirick DK, Stevens RG. Night shift work, light at night, and risk of breast cancer. J Natl Cancer Inst 2001;93:1557–62.[Abstract/Free Full Text]

2 Czeisler CA, Klerman EB. Circadian and sleep-dependent regulation of hormone release in humans. Recent Prog Horm Res 1999;54:97–130; discussion 130–2.[Medline]

3 Stevens RG, Rea MS. Light in the built environment: potential role of circadian disruption in endocrine disruption and breast cancer. Cancer Causes Control 2001;12:279–87.[Medline]

4 Leproult R, Colecchia EF, L'Hermite-Baleriaux M, Van Cauter E. Transition from dim to bright light in the morning induces an immediate elevation of cortisol levels. J Clin Endocrinol Metab 2001;86:151–7.[Abstract/Free Full Text]

5 Ticher A, Haus E, Ron IG, Sackett-Lundeen L, Ashkenazi IE. The pattern of hormonal circadian time structure (acrophase) as an assessor of breast cancer risk. Int J Cancer 1996;65:591–3.[Medline]

6 Zheng W, Jin F, Dunning LA, Shu XO, Dai Q, Wen WQ, et al. Epidemiological study of urinary 6beta-hydroxycortisol to cortisol ratios and breast cancer risk. Cancer Epidemiol Biomarkers Prev 2001;10:237–42.[Abstract/Free Full Text]

7 Funk D, Amir S. Conditioned fear attenuates light-induced suppression of melatonin release in rats. Physiol Behav 1999;67:623–6.[Medline]

8 Stevens RG. Electric power use and breast cancer: a hypothesis. Am J Epidemiol 1987;125:556–61.[Medline]



             
Copyright © 2002 Oxford University Press (unless otherwise stated)
Oxford University Press Privacy Policy and Legal Statement