Mechanisms of Breast Cancer in Shift Workers: DNA Methylation in Five Core Circadian Genes in Nurses Working Night Shifts.

2.50
Hdl Handle:
http://hdl.handle.net/10146/618168
Title:
Mechanisms of Breast Cancer in Shift Workers: DNA Methylation in Five Core Circadian Genes in Nurses Working Night Shifts.
Authors:
Samulin Erdem, Johanna; Skare, Øivind; Petersen-Øverleir, Marte; Notø, Heidi Ødegaard; Lie, Jenny-Anne S; Reszka, Edyta; Pepłońska, Beata; Zienolddiny, Shanbeh
Abstract:
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.
Affiliation:
Nofer Institute of Occupational Medicine, Łódź, Poland
Citation:
J Cancer 2017, 8 (15):2876-2884
Journal:
Journal of Cancer
Issue Date:
2017
URI:
http://hdl.handle.net/10146/618168
DOI:
10.7150/jca.21064
PubMed ID:
28928877
Additional Links:
http://www.jcancer.org/v08p2876.htm
Type:
Article
Language:
en
ISSN:
1837-9664
Sponsors:
This project was supported by the Norway Grants, under the Polish-Norwegian Research Program (Grant no. Pol-Nor/196940/22/2013-clock shift). JSE acknowledges a postdoctoral fellowship from NIOH.
Appears in Collections:
Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorSamulin Erdem, Johannaen
dc.contributor.authorSkare, Øivinden
dc.contributor.authorPetersen-Øverleir, Marteen
dc.contributor.authorNotø, Heidi Ødegaarden
dc.contributor.authorLie, Jenny-Anne Sen
dc.contributor.authorReszka, Edytaen
dc.contributor.authorPepłońska, Beataen
dc.contributor.authorZienolddiny, Shanbehen
dc.date.accessioned2017-10-20T09:21:14Z-
dc.date.available2017-10-20T09:21:14Z-
dc.date.issued2017-
dc.identifier.citationJ Cancer 2017, 8 (15):2876-2884en
dc.identifier.issn1837-9664-
dc.identifier.pmid28928877-
dc.identifier.doi10.7150/jca.21064-
dc.identifier.urihttp://hdl.handle.net/10146/618168-
dc.description.abstractShift 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.en
dc.description.sponsorshipThis project was supported by the Norway Grants, under the Polish-Norwegian Research Program (Grant no. Pol-Nor/196940/22/2013-clock shift). JSE acknowledges a postdoctoral fellowship from NIOH.en
dc.language.isoenen
dc.relation.urlhttp://www.jcancer.org/v08p2876.htmen
dc.rightsArchived with thanks to Journal of Canceren
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/*
dc.subjectshift worken
dc.subjectbreast canceren
dc.subjectcircadianen
dc.subjectpolymorphismen
dc.titleMechanisms of Breast Cancer in Shift Workers: DNA Methylation in Five Core Circadian Genes in Nurses Working Night Shifts.en
dc.typeArticleen
dc.contributor.departmentNofer Institute of Occupational Medicine, Łódź, Polanden
dc.identifier.journalJournal of Canceren

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