Clock on: gene variants and night shifts up breast cancer risk

Night working on laptop
The findings are consistent with the current way of thinking which considers the link between night work and disruption of the production of the hormone melatonin, which normally has its peak at night.
Dr Shanbeh Zienolddiny
Variations in the genes responsible for circadian rhythms can increase or decrease the likelihood that women who work night shifts will develop breast cancer, according to researchers in Norway…

Research from the National Institute of Occupational Therapy (STAMI) in Norway has illustrated the complex nature of the genes that influence cancer susceptibility. A paper published in the latest edition of BioMed Central’s open access journal Breast Cancer Research describes the results of a study of more than 1000 Norwegian nurses which aimed to investigate the association between night work associated breast cancer risk and variation in so-called ‘clock genes’.

The association between working nights and an elevated risk of breast cancer is such that the International Agency for Research on Cancer deems shiftwork which is disruptive of circadian patterns ’probably carcinogenic to humans’. However, the workings of the mechanisms behind this link remain unclear.

ScienceOmega.com’s questions about the findings were addressed by Dr Shanbeh Zienolddiny, a senior researcher in the Department of Chemical and Biological Working Environment.

Two-fold risk


As Dr Zienolddiny indicated, a number of past studies have demonstrated that the incidence of breast cancer among shift working female nurses is higher than expected.

"In a previous study published in the American Journal of Epidemiology in 2011, we found that the risk of breast cancer in night working nurses was almost twice as high as it was in nurses who worked only day shifts," he said.

The researchers found that the significance of the effect depended on the number of night shifts worked; the risk was two-fold only for nurses who had worked six or more consecutive nights per month for at least five years.

The current paper links this increased risk with polymorphism – natural variation – in clock genes which code for the proteins that control the so-called ‘biological clock’.

"The biological clock controls the 24 hour rhythms of the body," said Dr Zienolddiny. "Like other genes, individuals in a population will carry different variants of the clock genes as part of the normal genetic variation which makes individuals different from each other.

"The findings are consistent with the current way of thinking which considers the link between night work and disruption of the production of the hormone melatonin, which normally has its peak at night."

No simple explanation
 

Specifically, the authors associated an increased susceptibility to breast cancer with two variations of the AANAT gene, which codes for serotonin N-acetyltransferase – an enzyme involved in the manufacture of melatonin. Meanwhile, specific variants of the CLOCK gene (which controls circadian rhythms) and BMAL1 (which is responsible for a protein which binds to the protein produced by CLOCK) were associated with decreased risk.   

"The research points to individual differences in the risk of breast cancer related to night work," Dr Zienolddiny explained. "It further indicates that the disease is complex and there is no simple explanation for why some individuals are more susceptible."

As a further example of the complexity of the processes involved, the team found another variant of CLOCK was related to a reduced risk of breast cancer in women who worked three successive nights, but an increased risk in those who worked four or more night shifts in a row. Clearly there are questions left to be answered about the role of clock genes, the mechanisms of cancer risk, and the dangers of night shift work.

"The findings are simple associations found between some clock gene variants and breast cancer risk in shift workers," Dr Zienolddiny concluded. "We need to do further molecular analysis in order to understand the biology behind these associations."


Read the full text of the article, Analysis of polymorphisms in the circadian-related genes and breast cancer risk in the Norwegian nurses working night shifts...

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