The Influence of Shift Work, Light at Night and Clock Gene Polymorphisms on Melatonin Levels and Breast Cancer Risk

Abstract

Background: Shift work has recently been identified as a breast cancer risk factor, where meta-analysis has indicated an approximately 50% increased risk among long-term shift workers. However, additional studies with more comprehensive methods of shift work exposure assessment are needed to capture the diversity of shift patterns. The hypothesized mechanism for this relationship involves chronodisruption (altered circadian rhythms), where increased exposure to light at night during night shifts may decrease production of the cancer-protective hormone melatonin. Further, coordination of circadian rhythms, including melatonin production, is governed by the interactions of a set of central clock genes. Recent studies have suggested that variants in clock genes are associated with cancer risk at multiple sites, including breast cancer, although few studies have considered potential interactions with shift work.

Methods: This thesis examined relationships of both shift work and clock gene polymorphisms (and their interactions) with breast cancer risk in a case-control study of 1,142 cases and 1,178 controls. The association between light exposure and melatonin production was also investigated in a longitudinal biomarker study conducted among 123 nurses working a two-day, two-night rotating shift pattern.

Results: In the case-control study, an association between breast cancer and ≥30 years of shift work (OR = 2.20, 95%CI = 1.13 – 4.28) was detected, although no relationship with short (0 – 14 years) or medium (15 – 29 years) term shift work was observed. As well, variants in 14 clock-related genes were not associated with breast cancer and there were no apparent interactions with shift work history. In the biomarker study, both peak melatonin levels and daily change in melatonin levels were similar when nurses were working their day and night shifts. Further, on the night shift, a slight inverse relationship between light and change in melatonin was observed (p = 0.04).

Conclusions: Taken together, these results contribute to the understanding of both the association between shift work and breast cancer, and the biologic mechanisms underlying this relationship. Since shift work is required for many occupations, understanding the mechanisms through which it impacts breast cancer is important to the development of healthy workplace policy.