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Endocr Relat Cancer. 2014 Aug;21(4):629-38. doi: 10.1530/ERC-14-0121. Epub 2014 Jun 11.

Breast cancer risk, nightwork, and circadian clock gene polymorphisms.

Author information

1
InsermCESP Center for Research in Epidemiology and Population Health, U1018, Environmental Epidemiology of Cancer, Villejuif, FranceUniversité Paris-SudUMRS 1018, Villejuif, FranceBiostatistical UnitMRC, Cambridge, UKSchool of Mathematics and PhysicsThe University of Queensland, St Lucia, Queensland, AustraliaInsermCESP Center for Research in Epidemiology and Population Health, U1018, Epidemiology of Diabetes, Obesity and Chronic Kidney Disease Over Lifecourse, Villejuif, FranceUniversité Paris DescartesINSERM UMR-S775 EPIGENETEC, Paris, FranceDépartement d'informatique médicaleCenter Georges-François Leclerc, Dijon, FranceCenter Eugène MarquisRennes, FranceInsermCESP Center for Research in Epidemiology and Population Health, U1018, Environmental Epidemiology of Cancer, Villejuif, FranceUniversité Paris-SudUMRS 1018, Villejuif, FranceBiostatistical UnitMRC, Cambridge, UKSchool of Mathematics and PhysicsThe University of Queensland, St Lucia, Queensland, AustraliaInsermCESP Center for Research in Epidemiology and Population Health, U1018, Epidemiology of Diabetes, Obesity and Chronic Kidney Disease Over Lifecourse, Villejuif, FranceUniversité Paris DescartesINSERM UMR-S775 EPIGENETEC, Paris, FranceDépartement d'informatique médicaleCenter Georges-François Leclerc, Dijon, FranceCenter Eugène MarquisRennes, France.
2
InsermCESP Center for Research in Epidemiology and Population Health, U1018, Environmental Epidemiology of Cancer, Villejuif, FranceUniversité Paris-SudUMRS 1018, Villejuif, FranceBiostatistical UnitMRC, Cambridge, UKSchool of Mathematics and PhysicsThe University of Queensland, St Lucia, Queensland, AustraliaInsermCESP Center for Research in Epidemiology and Population Health, U1018, Epidemiology of Diabetes, Obesity and Chronic Kidney Disease Over Lifecourse, Villejuif, FranceUniversité Paris DescartesINSERM UMR-S775 EPIGENETEC, Paris, FranceDépartement d'informatique médicaleCenter Georges-François Leclerc, Dijon, FranceCenter Eugène MarquisRennes, France.
3
InsermCESP Center for Research in Epidemiology and Population Health, U1018, Environmental Epidemiology of Cancer, Villejuif, FranceUniversité Paris-SudUMRS 1018, Villejuif, FranceBiostatistical UnitMRC, Cambridge, UKSchool of Mathematics and PhysicsThe University of Queensland, St Lucia, Queensland, AustraliaInsermCESP Center for Research in Epidemiology and Population Health, U1018, Epidemiology of Diabetes, Obesity and Chronic Kidney Disease Over Lifecourse, Villejuif, FranceUniversité Paris DescartesINSERM UMR-S775 EPIGENETEC, Paris, FranceDépartement d'informatique médicaleCenter Georges-François Leclerc, Dijon, FranceCenter Eugène MarquisRennes, FranceInsermCESP Center for Research in Epidemiology and Population Health, U1018, Environmental Epidemiology of Cancer, Villejuif, FranceUniversité Paris-SudUMRS 1018, Villejuif, FranceBiostatistical UnitMRC, Cambridge, UKSchool of Mathematics and PhysicsThe University of Queensland, St Lucia, Queensland, AustraliaInsermCESP Center for Research in Epidemiology and Population Health, U1018, Epidemiology of Diabetes, Obesity and Chronic Kidney Disease Over Lifecourse, Villejuif, FranceUniversité Paris DescartesINSERM UMR-S775 EPIGENETEC, Paris, FranceDépartement d'informatique médicaleCenter Georges-François Leclerc, Dijon, FranceCenter Eugène MarquisRennes, France pascal.guenel@inserm.fr.

Abstract

Night shift work has been associated with an increased risk of breast cancer pointing to a role of circadian disruption. We investigated the role of circadian clock gene polymorphisms and their interaction with nightwork in breast cancer risk in a population-based case-control study in France including 1126 breast cancer cases and 1174 controls. We estimated breast cancer risk associated with each of the 577 single nucleotide polymorphisms (SNPs) in 23 circadian clock genes. We also used a gene- and pathway-based approach to investigate the overall effect on breast cancer of circadian clock gene variants that might not be detected in analyses based on individual SNPs. Interactions with nightwork were tested at the SNP, gene, and pathway levels. We found that two SNPs in RORA (rs1482057 and rs12914272) were associated with breast cancer in the whole sample and among postmenopausal women. In this subpopulation, we also reported an association with rs11932595 in CLOCK, and with CLOCK, RORA, and NPAS2 in the analyses at the gene level. Breast cancer risk in postmenopausal women was also associated with overall genetic variation in the circadian gene pathway (P=0.04), but this association was not detected in premenopausal women. There was some evidence of an interaction between PER1 and nightwork in breast cancer in the whole sample (P=0.024), although the effect was not statistically significant after correcting for multiple testing (P=0.452). Our results support the hypothesis that circadian clock gene variants modulate breast cancer risk.

KEYWORDS:

breast cancer; case–control study; circadian rhythm; nightwork

PMID:
24919398
DOI:
10.1530/ERC-14-0121
[Indexed for MEDLINE]
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