Night Shift Work and Endometrial Cancer
Night Shift Work and Endometrial Cancer
Abstract & Commentary
By William B. Ershler, MD, Editor
Synopsis: Night shift work has been shown to be associated with an increased risk of breast, colon and prostate cancer, presumably on the basis of diminished melatonin and its effects on hormonal and metabolic factors. In an analysis of the Nurses Health Study, data from 53,487 were examined with regard to night shift experience and the development of invasive endometrial cancer. From this population, 515 cases of endometrial cancer developed. Women who worked 20+ years of rotating night shifts, and obesity among night shift workers, were significant risk factors using Cox regression models.
Source: Viswanathan AN, et al. Night shift work and the risk of endometrial cancer. Cancer Res. 2007;67:10618-10622.
Social or environmental factors that alter hormonal homeostasis have been implicated in the causation of certain human malignancies, including breast, prostate, ovarian and endometrial cancer. Endometrial cancer, currently the most common gynecologic malignancy in the United States1 is more commonly observed in those with prolonged unopposed estrogen exposure.2 Thus, increased rates are observed in association with obesity or in women who receive postmenopausal hormonal therapy. Factors such as parity, age at first birth, oral contraceptive use, smoking, age at menarche, and menopause have all been related to endometrial cancer, presumably on the basis of their hormone modulating effects. Nulliparity, older age at first birth, early menarche, and late menopause increase the risk of endometrial cancer, whereas smoking and oral contraceptive use decrease it.2
Melatonin has been shown to have several oncostatic properties, including possible antiestrogenic and anti aromatase activity, and it seems also to be linked with fat metabolism. Night workers have lower levels of melatonin, which may predispose to cancer development. Indeed, observational studies have demonstrated higher risk of breast3, colorectal4, and prostate cancer5 among night workers. Viswanathan and colleagues hypothesized that night shift workers will also have an increased risk of endometrial cancer. To examine this they investigated data derived from the Nurses' Health Study.
The Nurses' Health Study began in 1976 when 121,701 female registered nurses between the ages of 30 and 55 years were surveyed. Since that time, biannual questionnaires addressed issues regarding health status, medical history, and risk factors for cancer and heart disease. Remarkably, follow-up data is available for more than 90% of the ongoing cohorts.6 Of the total population, 53,487 women provided data on rotating night shift work during the calendar year 1988, and these were followed through June 1, 2004. During this period a total of 515 women developed an invasive endometrial cancer. Using Cox regression analysis to calculate multivariate relative risks, the investigators discovered that women who worked for more than 20 years on a rotating night shift schedule had a significantly increased risk of endometrial cancer (RR, 1.47; 95% confidence interval [95% CI], 1.03-1.14). In stratified analyses, obese women working rotating night shifts doubled their baseline risk of endometrial cancer (RR, 2.09; 95% CI, 1.24-3.52) compared with obese women who did no night work.
The investigators speculated that this increased risk was attributable to effects of diminished melatonin in this population and the effects thereof on hormonal and metabolic homeostasis.
Commentary
These findings from a very large cohort are quite significant and biologically interesting. Although the role of melatonin is intriguing as speculated, no data was provided with regard to melatonin level among the night shift workers or in those with or without endometrial cancer. Melatonin secretion is abnormal in night workers, and the link with hormonal alterations and obesity is well established. However, a number of factors other than melatonin are also likely to be perturbed by long-term night duty and a full metabolic evaluation, at least on some of these patients and matched controls would likely be instructive, if not hypothesis generating.
Nonetheless, it is pretty clear that long-term night shift duty presents a risk for certain malignancies including endometrial cancer, and the relative risk for this malignancy may be two fold or higher if obesity is also present. This novel finding requires confirmation, but currently there is sufficient epidemiological data to warrant further study of the relationship between light exposure and cancer risk through the melatonin pathway.
References
1. Jemal A, et al. Cancer statistics, 2006. CA Cancer J Clin. 2006;56(2):106-130.
2. Kaaks R, et al. Obesity, endogenous hormones, and endometrial cancer risk: a synthetic review. Cancer Epidemiol Biomarkers Prev. 2002;11(12):1531-1543.
3. Megdal SP, et al. Night work and breast cancer risk: a systematic review and meta-analysis. Eur J Cancer. 2005;41(13):2023-2032.
4. Schernhammer ES, et al. Night-shift work and risk of colorectal cancer in the nurses' health study. J Natl Cancer Inst. 2003;95(11):825-828.
5. Kubo T, et al. Prospective cohort study of the risk of prostate cancer among rotating-shift workers: findings from the Japan collaborative cohort study. Am J Epidemiol. 2006;164(6):549-555.
6. Colditz GA, et al. The Nurses' Health Study: 20-year contribution to the understanding of health among women. J Womens Health. 1997;6(1):49-62.
Night shift work has been shown to be associated with an increased risk of breast, colon and prostate cancer, presumably on the basis of diminished melatonin and its effects on hormonal and metabolic factors.Subscribe Now for Access
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