Previous observational studies have suggested an association between night work and increased risk of breast cancer. This is a potentially important observation given the high prevalence of breast cancer and the number of women working night shifts. The mechanisms behind this association have not yet been determined, but it is hypothesised that exposure to light during the night may suppress nocturnal melatonin production, which effects patterns of sex hormone production, and in turn influences breast cancer risk.
New research published in Breast Cancer Research by Kristina Kjaerheim from the Cancer Registry of Norway and colleagues sheds more light on this association, finding significant associations between several polymorphisms in circadian genes, night work, and breast cancer.
The researchers conducted a nested case-control study to investigate the role of a number of circadian gene polymorphisms as potential biomarkers for susceptibility to night-work related breast cancer risk. From an existing cohort of Norwegian nurses aged 35-74 years they identified a group of 1182 nurses consisting of a ‘case’ group of 563 women who had histologically confirmed invasive breast cancer and 619 matched controls who did not have cancer. 60 SNPs in 17 genes from the circadian signalling pathway were studied and information was collected on the participants work schedule.
When night work was not taken into account, the researchers found four SNPs that were associated with breast cancer risk. Two polymorphisms in the AANAT gene were associated with an increased risk of breast cancer while polymorphisms in the BMAL1 and CLOCK genes were associated with a reduced risk.
When they also considered night work, those in the highest intensity group (working four or more consecutive night shifts) had an increased risk of breast cancer associated with polymorphisms in the AANAT gene. In those working three consecutive night shifts, a reduced risk of breast cancer was associated with polymorphisms in the CLOCK, ROR-b and MTNR1A genes.
The researchers then looked only at nurses who had worked night shifts for five or more years. They found that in those who had worked four or more consecutive night shifts, there was an increased risk of breast cancer associated with polymorphisms in BMAL1 and ROR-b. In those who worked three consecutive night shifts, SNPs in BMAL1, BMAL2, CSNK1E, NPAS2, PER3, and MTNR1A were associated with decreased breast cancer risk.
These results suggest that polymorphisms in some of the core circadian or melatonin signalling pathways may, in conjunction with night work, affect the risk of breast cancer and that this risk may be influenced by the intensity of night shift work and the number of years spent working nights. Confirmation and validation of these results is needed, but this research paves the way for future studies to look into the genetic and epigenetic functionality of these SNPs, as well as epigenetic changes in shift workers, to help understand the biological mechanisms underlying this association.
Analysis of polymorphisms in the circadian-related genes and breast cancer risk in Norwegian nurses working night shifts
Breast Cancer Research 2013, 15:R53
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