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2017 ; 8
(15
): 2876-2884
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Mechanisms of Breast Cancer in Shift Workers: DNA Methylation in Five Core
Circadian Genes in Nurses Working Night Shifts
#MMPMID28928877
Samulin Erdem J
; Skare Ø
; Petersen-Øverleir M
; Notø HØ
; Lie JS
; Reszka E
; Pep?o?ska B
; Zienolddiny S
J Cancer
2017[]; 8
(15
): 2876-2884
PMID28928877
show ga
Shift work has been suggested to be associated with breast cancer risk, and
circadian disruption in shift workers is hypothesized as one of the mechanisms of
increased cancer risk. There is, however, insufficient molecular evidence
supporting this hypothesis. Using the quantitative methodology of pyrosequencing,
epigenetic changes in 5-methyl cytosine (5mC) in five circadian genes CLOCK,
BMAL1, CRY1, PER1 and PER2 in female nurses working night shift work (278 breast
cancer cases, 280 controls) were analyzed. In breast cancer cases, a medium
exposure to night work was associated with increased methylation levels of the
CLOCK (p=0.050), BMAL1 (p=0.001) and CRY1 (p=0.040) genes, compared with
controls. Within the cases, analysis of the effects of shift work on the
methylation patterns showed that methylation of CRY1 was lower in those who had
worked night shift and had a high exposure (p=0.006) compared with cases that had
worked only days. For cases with a medium exposure to night work, an increase in
BMAL1 (p=0.003) and PER1 (p=0.035) methylation was observed compared with day
working (unexposed) cases. The methylation levels of the five core circadian
genes were also analyzed in relation to the estrogen and progesterone receptors
status of the tumors in the cases, and no correlations were observed.
Furthermore, nineteen polymorphisms in the five circadian genes were assessed for
their effects on the methylation levels of the respective genes, but no
associations were found. In summary, our data suggest that epigenetic regulation
of CLOCK, BMAL1, CRY1 and PER1 may contribute to breast cancer in shift workers.
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