| An increased risk of breast cancer in night workers may in part be mediated by the melatonin pathway
Previous observational studies, prompted by the theory that melatonin suppression increases cancer risk, suggest a positive association between night work and breast cancer risk. Melatonin, a hormone with potential oncostatic activity, is produced almost exclusively during the night and is acutely suppressed by exposure to light at night such as in night workers. However, the relationship between circulating melatonin levels and breast cancer risk remains unclear. To further evaluate the melatonin hypothesis, we
prospectively examined associations between history of night work in
nurses and breast cancer risk in the Nurses'
Health Study II (NHSII). We also examined associations between urinary
melatonin levels and subsequent breast cancer risk.Participants included
115,022 predominantly premenopausal women who were free of cancer at
baseline in 1989. Of these, 1,352 were diagnosed with invasive breast
cancer during 12 years of follow-up. At baseline and at 2 to 4 year
intervals, we assessed the number of years the nurses worked rotating
night shifts defined as at least three nights per month. As part of a
case-control study nested within the NHSII cohort, we evaluated morning
levels of urinary 6-sulfatoxy (aMT6s) melatonin in 190 women who developed
breast cancer during 4 years of follow-up and in 376 matched controls.
Samples were collected between 1996 and 1998. We used Cox proportional
hazards models to evaluate associations between duration of night shift
work and breast cancer risk, adjusting for several breast cancer risk
factors. We used logistic regression to evaluate associations of urinary
melatonin and breast cancer risk. Women reporting more than 20 years of
rotating night shift work experienced an elevated age-adjusted relative
risk of breast cancer compared to women who did not engage in rotating
night shift work (RR,
1.88; 95% CI, 1.12 to 3.15). After further adjustment for several
important breast cancer risk factors, the association was virtually
unchanged (RR, 1.79; 95% CI, 1.06-3.01). Assessed at baseline, having
worked rotating night shifts for more than 20 years was also significantly
associated with breast cancer risk (multivariate RR, 2.79, 95% CI,
1.38-5.66), compared to women without any night work. In contrast, there
was no increase in risk associated with an intermediate number of years of
rotating night work (RR, 1.0, 0.98, and 0.91 for 0, 1-9, and 10-19 years
of night work, respectively). Controlling for matching factors, the RR of
invasive breast cancer associated with the lowest compared with the
highest quartile of urinary aMT6s was 1.70 (95% CI, 1.04-2.78).
Associations were similar after further adjustment for breast cancer risk
factors (RR, 1.70; 95% CI, 1.02-2.82) and plasma sex
hormone levels and after the exclusion of night workers (RR, 1.67; 95% CI,
0.97-2.90).
Bibliographical references:
Eva
Schernhammer
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