Abstract A01: Mechanisms of breast cancer risk in shift workers: Epigenetic changes in the circadian pathway

Abstract

Abstract Occupational factors such as shiftwork and especially night work that involves disruption of the circadian rhythm can increase breast cancer risk. Circadian disruption may also affect epigenetic factors such as 5-methyl cytosine methylation in DNA. DNA hypermethylation generally is associated with increased cancer risk, if it occurs in tumor suppressor genes. Some of the circadian genes are known to function as tumor suppressor genes. DNA methylation in cirdavdian genes and its association with breast cancer risk in shiftworkers is little investigated and the limited available data are inconclusive. We here investigated DNA methyalation at 5-meC sites in the promoter regions of core circadian and melatonin receptor genes as a potential mechanism for night work-related breast cancer risk. A nested breast cancer case-control study of nurses working night shifts comprising of seven-hundred breast cancer cases and matched controls was conducted. Methylation at 5-meC sites in a number of core circadian and melatonin receptor genes was in DNA from sputum samples obtained from cases and controls. Changes in methylation status of the 5-meC in DNA (methylation index) and the odds of breast cancer associated with DNA methylation was calculated in relation to the duration and intensity of night shiftwork. We demonstrate that generally the methylation of 5-meC is low for all the genes that were analyzed. However, we will present analyses of the effects of work schedules and duration, as number of consecutive night shifts, on epigenetic changes. The hypothesis is that increased breast cancer risk in workers with long periods of consecutive night shifts may be associated with changes in methylation status of the genes regulation the circadian rhythm. Citation Format: Shan Zienolddiny. Mechanisms of breast cancer risk in shift workers: Epigenetic changes in the circadian pathway [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr A01.