A cross-sectional study of breast cancer biomarkers among shift working nurses

Objectives: In 2007, the International Agency for Research on Cancer classified long-term shift work as a probable carcinogen, with the strongest evidence for breast cancer. One proposed mechanism involves night-time light exposure and decreases in melatonin, a circadian rhythmic hormone. It is hypothesised that melatonin influences patterns of sex hormone production that in turn influence breast cancer risk. This study sought to investigate the relationships of shift work history, 6-sulfatoxymelatonin (aMTs-6, the primary melatonin metabolite) and sex hormone levels among shift working nurses. Design: This is a cross-sectional biomarker study. Setting: 94 premenopausal nurses who work a full-time rotating shift schedule at one Ontario hospital were recruited for this study; 82 completed follow-up. Primary and secondary outcome measures: Study participants provided morning void urine and fasting blood samples for the assessment of aMTs-6 and sex hormone (oestradiol, oestrone, progesterone, prolactin) levels, respectively. These data were collected at two time points (summer and winter) such that relationships between melatonin and sex hormones could be assessed with respect to two time frames of interest (acute and cross-seasonal). Results: An inverse relationship between aMTs-6 and oestradiol was suggested in the winter (beta = -0.18, p = 0.04), but this result was not statistically significant in multivariate modelling that adjusted for age, body mass index and menstrual cycle. Likewise, while oestradiol, oestrone and progesterone levels increased with greater years of shift work history (all p<0.05), these associations were attenuated after confounder adjustment. Conclusions: These results do not support the proposed relationship between melatonin and sex hormone levels as biomarkers on the pathway of shift work and breast cancer but emphasise the importance of adjusting for confounders in modelling.