Background Shift work has been proposed as a risk factor for a number of diseases including cancer and the International Agency for Research on Cancer has classified shift work that involves circadian disruption as probably carcinogenic. A number of mechanisms may underlie these associations, including those related to suppressed melatonin production, sleep disturbance and confounding by other behavioural or lifestyle factors. I will review the epidemiological evidence on shift work and cancer, and will present data from the Million Women Study on the characteristics of shift workers and from the Guernsey Study on the relationship between melatonin and breast cancer risk.

Methods We compared the characteristics of British women from the Million Women Study who had and had not worked at night in terms of their risk factors for common disease using data from 41,652 women who reported their history of night work in 2009–2010. We also examined the association between nocturnal melatonin and breast cancer risk in a case-control study nested within the Guernsey III Study, a British prospective cohort study. We measured concentrations of 6-sulfatoxymelatonin in prediagnostic first-morning urine samples from 251 breast cancer cases and 727 matched controls and used conditional logistic regression models to calculate odds ratios for breast cancer in relation to 6-sulfatoxymelatonin level.

Results The published epidemiological evidence is suggestive but not conclusive for an adverse association between shift work, particularly long-term night work, and breast cancer risk, while the data are more limited and inconsistent for cancers at other sites and all cancers combined. Results from the Million Women Study, however, showed that women who reported ever having worked at night were substantially different from those who reporting never having worked at night and many of the differences would put "ever night workers" at increased risks of cancer. For melatonin, while there was no evidence for an association with breast cancer risk among British women, overall the published data suggest a modest inverse association between melatonin levels and breast cancer risk (for highest fourth versus lowest, odds ratio = 0.81, 95% confidence interval: 0.66, 0.99).

Conclusion Published data are suggestive but not conclusive for an adverse association between night work and breast cancer and, correspondingly, for a protective association between melatonin and risk for the disease. However, there are several limitations of the epidemiological evidence including the relatively limited data from large prospective population-based investigations and inconsistent consideration of the role of potential confounders.