February 24, 2014

Night Shift Work Decreases Risk of Melanoma

Surprising findings from the Nurses' Health Study
It is possible that higher melatonin levels may be beneficial in people with stable circadian rhythms, but in night workers with unstable rhythms, simple suppression of melatonin may be more beneficial.


Schernhammer ES, Razavi P, Li TY, Qureshi AA, Han J. Rotating night shifts and risk of skin cancer in the Nurses' Health Study. J Natl Cancer Inst. 2011;103(7):602-606.


Retrospective statistical analysis of data collected in the Nurses’ Health Study


Of 68,336 women in the Nurses' Health Study tracked from June 1988 to June 2006, there were 10,799 incident skin cancers. Data from these women were utilized.

Study Methodology

The relationship between working rotating night shifts and skin cancer was explored using Cox proportional hazard models, adjusted for confounding variables such as phenotypic and established risk factors of skin cancer.

Outcome Measures

Development of skin cancer. Basal cell, squamous cell, and melanoma cases were tracked.

Key Findings

Working 10 years or more on rotating night shifts was associated with a 14% decreased risk of skin cancer compared with never working night shifts (HR=0.86; 95% CI=0.81–0.92). This benefit of night work was strongest for melanoma; working 10 years or more of rotating night shifts was associated with 44% decreased risk of melanoma (HR=0.56; 95% CI=0.36–0.87).


These results are not what we would have predicted. This study found that for women, working night shifts was associated with a lower of risk of developing melanoma
For the past 2 decades Eva Schernhammer, the principle author of this study, and her colleagues at the Harvard School of Medicine have been publishing research on melatonin and cancer risk. One focus of their research has been the association between working night shifts and risk of cancer. In 2001 using data collected from the 78,562 women in the Nurses' Health Study, they reported an association between night work and breast cancer. In their analysis there were moderate increases in risk for women who worked up to 29 years on rotating night shifts. Risk of breast cancer increased to 36% in women who had worked 30 or more years of rotating night shifts (RR=1.36; 95% CI=1.04–1.78).1
In 2003 Schernhammer et al reported a more significant increase in risk for colorectal cancer in night shift workers. Those who had worked more than 15 years of night shifts had a 44% increased risk of developing colorectal cancer (RR=1.44; CI=1.10–1.89).2
Other studies have linked night shift work with increased risk for other malignancies, including endometrial,3 prostate,4 and non-Hodgkin’s lymphoma.5
Working night shifts has also been associated with increased risk of chronic non-malignant disease, such as gastrointestinal disorders, cardiovascular disease, stroke, and diabetes.6,7,8,9 The only exception to this pattern of night shift work worsening risk of any chronic disease until this current paper was Parkinson’s disease. A 2006 paper by Chen et al reported that nurses who had worked 15 or more years on rotating night shifts had half the risk of developing Parkinson’s disease as nurses who had never worked night shifts. Their data suggest a good night’s sleep is a bad thing. The longer a nurse slept, the higher the risk for Parkinson’s. Comparing those who slept 9 or more hours per day with those who slept 6 hours or less, the nurses who slept longer had an 84% increase in risk.10
It is interesting to note that people who develop Parkinson’s disease are at lower risk of getting cancer. It has been hypothesized that melatonin may in some way aggravate or trigger this disease, and that limiting melatonin production may slow disease progression.11 In other words, sleeping with the lights on may protect you from Parkinson’s even if it increases your risk for breast or colorectal cancer.
It is possible that higher melatonin levels may be beneficial in people with stable circadian rhythms, but in night workers with unstable rhythms, simple suppression of melatonin may be more beneficial.
The assumption has been that working night shifts disrupted melatonin production, and the workers lost the protective benefit conveyed by melatonin against cancer. With breast cancer in particular, the hypothesis has been that nighttime melatonin suppressed estrogen production, thereby lowering risk of breast cancer.
The actual relationship may be more complicated than this. In 2008 Nagata et al, after measuring hormone levels in 2,006 postmenopausal women who worked graveyard shifts, reported that although the estrogens estrone and estradiol were elevated in these nighttime wakeful women, melatonin levels did not correlate with estrogen levels. While “exposure to light at night has implications for the risk of breast cancer in postmenopausal women … the potential role of melatonin as an intervening factor between light exposure at night and the serum concentrations of estrogen was equivocal.”12
In the current Schernhammer paper, the simplest explanation for the association between night-shift work and decreased skin cancer risk would be lack of sun exposure. The authors ruled out this possibility, assuming that if daytime sun exposure had been a factor they would have seen geographical variations in their results, which they did not.
Past experimental studies provide strong evidence that melatonin is oncostatic and can reduce the growth of malignant melanoma, but the matter isn’t straightforward. Time of administration of melatonin changes its effect. Effects also may vary with concentration. In one study, low doses inhibited melanoma growth while higher doses had no effect.13
Although our long-held assumption has been that the negative effects of shift work are due to melatonin suppression, we may be wrong. A September 2011 article in Medical Hypothesis suggests 4 other possible explanations for the effects. The authors suggest we also consider the impact of phase shift, sleep disruption, and impact night work on lifestyle, diet, and physical activity. There is also the possibility of lower vitamin D levels that result from lack of sun exposure.14 In this current study, low vitamin D is probably not the explanation for the effects: The researchers did track time spent outside in the sun and found no correlation with melanoma risk.
It is possible that higher melatonin levels may be beneficial in people with stable circadian rhythms, but in night workers with unstable rhythms, simple suppression of melatonin may be more beneficial.
In Schernhammer’s current paper, the inverse association between melanoma and night shift work was strongest in women with black or brown hair. This certainly suggests a genetic variation in reaction to night work and possibly to melatonin. Dark hair contains higher levels of tryptophan and melatonin than light colored hair.15 Could these biological differences in some way have an impact?

Practice Implications

The results of this current study strongly suggest that the role circadian disruption plays in melanoma may be more complex than previously thought. While it is a common practice to supplement cancer patients with nighttime melatonin, we should perhaps hesitate to suggest this to patients with melanoma.

Categorized Under


1. Schernhammer ES, Laden F, et al. Rotating night shifts and risk of breast cancer in women participating in the nurses' health study. J Natl Cancer Inst. 2001;93(20):1563-1568.
2. Schernhammer ES, Laden F, Speizer FE, et al. Night-shift work and risk of colorectal cancer in the nurses' health study. J Natl Cancer Inst. 2003;95(11):825-828. (Free full text: http://jnci.oxfordjournals.org/content/95/11/825.full.pdf+html)
3. Viswanathan AN, Hankinson SE, Schernhammer ES. Night shift work and the risk of endometrial cancer. Cancer Res. 2007;67(21):10618-10622.
4. Conlon M, Lightfoot N, Kreiger N. Rotating shift work and risk of prostate cancer. Epidemiology. 2007;18(1):182-183.
5. Lahti TA, Partonen T, Kyyrönen P, Kauppinen T, Pukkala E. Night-time work predisposes to non-Hodgkin lymphoma. Int J Cancer. 2008;123(9):2148-2151.
6. Knutsson A. Health disorders of shift workers. Occup Med (Lond). 2003;53(2):103-108.
7. Karlsson B, Alfredsson L, Knutsson A, Andersson E, Torén K. Total mortality and cause-specific mortality of Swedish shift- and dayworkers in the pulp and paper industry in 1952–2001. Scand J Work Environ Health. 2005;31(1):30-35.
8. Knutsson A, Bøggild H. Gastrointestinal disorders among shift workers. Scand J Work Environ Health. 2010;36(2):85-95.
9. Hermansson J, Gillander Gådin K, Karlsson B, Lindahl B, Stegmayr B, Knutsson A. Ischemic stroke and shift work. Scand J Work Environ Health. 2007;33(6):435-439.
10. Chen H, Schernhammer E, Schwarzschild MA, Ascherio A. A prospective study of night shift work, sleep duration, and risk of Parkinson's disease. Am J Epidemiol. 2006;163(8):726-730.
11. Schernhammer E, Chen H, Ritz B. Circulating melatonin levels: possible link between Parkinson's disease and cancer risk? Cancer Causes Control. 2006;17(4):577-582.
12. Nagata C, Nagao Y, Yamamoto S, Shibuya C, Kashiki Y, Shimizu H. Light exposure at night, urinary 6-sulfatoxymelatonin, and serum estrogens and androgens in postmenopausal Japanese women. Cancer Epidemiol Biomarkers Prev. 2008;17(6):1418-1423.
13. Otálora BB, Madrid JA, Alvarez N, Vicente V, Rol MA. Effects of exogenous melatonin and circadian synchronization on tumor progression in melanoma-bearing C57BL6 mice. J Pineal Res. 2008;44(3):307-315.
14. Fritschi L, Glass DC, Heyworth JS, et al. Hypotheses for mechanisms linking shiftwork and cancer. Med Hypotheses. 2011;77(3):430-436.
15. Bertazzo A, Biasiolo M, Costa CV, Cardin de Stefani E, Allegri G. Tryptophan in human hair: correlation with pigmentation. Farmaco. 2000;55(8):521-525.