Through a collaborative initiative, Polish and Norwegian researchers will investigate and test mechanistic hypotheses, addressing issues relevant to breast cancer development in women working night shifts. The primary research focus will be examining the relationship between shift work with night work and breast cancer risk, as well as investigating epigenetic changes associated with such work.

Analysis of methylation levels

An important epigenetic mechanism is changes in the level of 5-methylcytosine in gene promoter regions. Alterations in methylation levels can impact gene expression, and such changes are often found in cancer cells. One focus of the project is therefore to analyse the methylation status in the promoter regions of circadian rhythm genes, oestrogen and progesterone receptor genes, cell cycle and cancer-inhibiting genes, and melatonin receptor genes.

Project design

Data and biological samples from two epidemiological studies will be used. The first is a case-control study of nurses in Norway, while the second is a cross-sectional study of nurses and midwives in Poland. In the Norwegian study, the methylation level in DNA from breast cancer patients will be compared with DNA from healthy controls. Associations between lifestyle factors (diet, smoking, alcohol consumption, physical activity, and sleep deprivation) and the methylation level of cancer-inhibiting genes will be examined. In both studies, the impact of working night shifts on epigenetic changes will be analysed. Because some epigenetic events can be prevented, the results from these studies may lead to new strategies for cancer prevention.

About the cohort

In 2004, based on information from the Norwegian Board of Health Supervision’s register of nurses, a cohort was established which consisted of 49 402 female nurses who graduated between 1914 and 1985. Within this cohort, an interview-based case-control study of 1182 women was initiated (for details, see Lie et al. 2011). Women between 35-74 years, diagnosed with histologically confirmed breast cancer between 1990 and 2007 and alive before February 2009, were included in the study. All women had worked as nurses for at least one year and consented to be interviewed. Healthy nurses were recruited as controls. Saliva samples were collected from a total of 563 participants and 619 healthy controls, and DNA was isolated from these samples.

Main objectives

  • To investigate whether night shift work has an epigenetic effect on the methylation pattern of selected circadian rhythm and cell cycle-regulating genes.
  • To examine whether there are differences between breast cancer patients and healthy controls regarding the methylation pattern of core circadian genes, melatonin receptor genes, and female hormone receptor genes.


Differential methylation patterns in circadian- and melatonin-related genes and telomere length in breast cancer cases and healthy controls who worked shiftwork was found, indicating that epigenetic regulation of these genes may contribute to breast cancer risk in shift workers.

The project resulted in one PhD degree, and one master thesis.

Project group

Shan Narui, Jenny-Anne Sigstad Lie

Collaborative partners

Dr. Kristina Kjærheim, Cancer Registry, Norway
Dr. Beata Peplonska, Nofer Institute of Occupational Medicine, Lodz, Poland