CLOCKSHIFT

Breast cancer risk and epigenetic effects of the rotating night shift work and lifestyle.

Aims

Our specific aims are:

1. To determine whether night shift work has an epigenetic impact on the global methylation and promoter methylation patterns in core circadian genes (PER1, PER2, PER3, BMAL1, CLOCK, CRY1, CRY2, NPAS2) and cell cycle regulatory genes (TP53, CDKN1A, CDKN2A, RB1, BRCA1, BRCA2).

2. To determine whether promoter methylation patterns in the core circadian genes (PER1, PER2, BMAL1, CLOCK, CRY1), melatonin receptor genes (MTNR1A, MTNR1B) and sex-hormone receptor genes (ER-a, ER-b, PR) differs between breast cancer cases and controls.

3. To investigate associations between night shift work and sleep pattern (with chronotype as potential modifying factor), selected dietary factors (folates intake), obesity, alcohol consumption, smoking, physical activity, sleep deprivation and  associations between lifestyle factors and promoter methylation pattern in the cell cycle regulatory genes (TP53, CDKN1A, CDKN2A, RB1, BRCA1, BRCA2).

4. To investigate associations between night shift work exposure and hormone concentrations (estradiol, testosterone, and DHEAS), and associations between hormone concentrations and promoter methylation patterns in the core circadian genes (PER1, PER2, PER3, BMAL1, CLOCK, CRY1, CRY2, NPAS2).