Increased Risk for Breast Cancer in Shift Workers Possibly Associated with Epigenetic Changes in Circadian Pathway

TON - March 2017, Vol 10, No 2

Cape Town, South Africa—Occupational factors such as shift work disrupt circadian rhythm and can increase breast cancer risk, and the International Agency for Research on Cancer (the World Health Organization’s source for information about cancer) has classified shift work as a possible carcinogen. However, according to researchers at the National Institute of Occupational Health in Oslo, Norway, and the Nofer Institute of Occupational Medicine in Lodz, Poland, the mechanisms of increased cancer risk caused by shift work are not fully understood.

Circadian disruption may affect epigenetic factors such as 5-methyl cytosine methylation in DNA. DNA hypermethylation is associated with increased cancer risk if it occurs in tumor suppressor genes, and some circadian genes are known to function as tumor suppressor genes. The re­searchers, led by Shan Zienolddiny from the National Institute of Occupational Health, hypothesized that these aberrant epigenetic modifications caused by circadian disruption may be involved in the development of breast cancer.

The team conducted a nested breast cancer case-control study of female nurses working night shifts and presented their results in a poster at the American Association for Cancer Research International Conference on New Frontiers in Cancer Research. Changes in methylation levels in a number of core circadian and melatonin receptor genes were analyzed in 352 patients with breast cancer and 355 healthy controls.

Significantly higher methylation in the MTNR1A gene was observed in patients with cancer than in controls, and PR-A methylation was significantly increased in night workers compared with day workers. Based on these data, the investigators concluded that changes in methylation status of the genes that regulate circadian rhythm may be associated with increased breast cancer risk in workers with consecutive night shifts. However, further research is needed on the effects of work schedules on epigenetic changes.—MB

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