Rotating Night Shifts and Risk of Breast Cancer in Women Participating in the Nurses' Health Study

TLDR: Women who work on rotating night shifts with at least three nights per month, in addition to days and evenings in that month, appear to have a moderately increased risk of breast cancer after extended periods of working rotating night shift.

Abstract: Background: Melatonin shows poten-tial oncostatic action,and light expo-sure during night suppresses melatoninproduction. There is little information,however,about the direct effect ofnight work on the risk of cancer. Weinvestigated the effect of night work inbreast cancer. Methods: We examinedthe relationship between breast cancerand working on rotating night shiftsduring 10 years of follow-up in 78562women from the Nurses’ Health Study.Information was ascertained in 1988about the total number of years duringwhich the nurses had worked rotatingnight shifts with at least three nightsper month. From June 1988 throughMay 1998,we documented 2441 inci-dent breast cancer cases. Logistic re-gression models were used to calculaterelative risks (RRs) and 95% confi-dence intervals (CIs),adjusted for con-founding variables and breast cancerrisk factors. All statistical tests weretwo-sided. Results: We observed a mod-erate increase in breast cancer riskamong the women who worked 1–14years or 15–29 years on rotating nightshifts (multivariate adjusted RR = 1.08[95% CI = 0.99 to 1.18] and RR = 1.08[95% CI = 0.90 to 1.30],respectively).The risk was further increased amongwomen who worked 30 or more yearson the night shift (RR = 1.36; 95% CI =1.04 to 1.78). The test for trend was sta-tistically significant ( P = .02).Conclu-sions: Women who work on rotatingnight shifts with at least three nightsper month,in addition to days and eve-nings in that month,appear to have amoderately increased risk of breastcancer after extended periods of work-ing rotating night shifts. [J Natl CancerInst 2001;93:1563–8]The suprachiasmatic nucleus in the hy-pothalamus, one of the most importantphysiologic determinants of alertness andperformance, drives a circadian pace-maker in mammals, with an intrinsic pe-riod averaging 24 hours. Light is the pri-mary stimulus to disrupt and reset thispacemaker, which is expressed in chang-ing melatonin rhythms. Light exposure atnight may, therefore, be related to a vari-ety of behavioral changes and associatedhealth problems not yet well explored.Studies (1)have suggested an increasedrisk of coronary heart disease among ro-tating night shift workers, not fully ex-plained by an increased prevalence ofcoronary risk factors. Others have linkednight work to an increased breast cancerrisk among women (2).Melatonin, the “hormone of the dark-ness,” has only recently gained substantialattention from the scientific communitywith regard to its potential oncostatic ac-tions and its possible effect on breast can-cer risk (3–10).Melatonin serum levels inhumans decrease when people are ex-posed to light at night (11).Suppressedserum melatonin levels might enhance tu-mor development (12).Observationalstudies (2,13–15)are compatible with aneffect of melatonin on breast cancer risk,reporting meaningful increases in breastcancer risk among postmenopausal womenexposed to shiftwork. Recently, a tumor-promoting effect of light exposure wasdemonstrated on chemically induced tu-mors in rodents (16).To date, melatoninhas been shown to be oncostatic for a va-riety of tumor cells in experimental car-cinogenesis (17–26).The evidence of arelation between melatonin and oncogen-esis in humans is conflicting (27),butthe majority of reports indicate protectiveaction (28).Several mechanisms have been hy-pothesized to explain an association be-tween melatonin and breast cancer. Cohenet al. (29)proposed that loss of pinealfunction and the resulting decreased mel-atonin serum levels may increase repro-ductive hormone levels and, in particular,estradiol levels, thereby increasing thegrowth and proliferation of hormone-sensitive cells in the breast. More recentresearch focuses on potential mechanismsthrough which melatonin is directly onco-static. Melatonin is believed to have anti-mitotic activity by affecting directly hor-mone-dependent proliferation throughinteraction with nuclear receptors (4).An-other explanation is that melatonin in-creases the expression of the tumor sup-pressor gene p53 (3).Cells lacking p53have been shown to be genetically un-stable and thus more prone to tumors (30).Breast cancer is the most common can-cer among women in the United States.To date, the relationship between nightwork and breast cancer risk has not beenevaluated in prospective cohort studies. Acausal link between the two would be ofpublic health importance, because smallchanges in shift patterns may create a sub-stantial decrease of disease burden amongwomen.In this report, we evaluate the relation-ship between night work, as a surrogatefor light exposure at night, and breastcancer risk in a large prospective cohortof premenopausal and postmenopausalwomen. Our analysis is based on 10 yearsof follow-up in 78562 women participat-ing in the Nurses’ Health Study.