title: Breast cancer risk, nightwork, and circadian clock gene polymorphisms.
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.
authors.affiliation: 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.
authors.forename: Thérèse
authors.initials: T
authors.lastname: Truong
authors.affiliation: 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.
authors.forename: Benoît
authors.initials: B
authors.lastname: Liquet
authors.affiliation: 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.
authors.forename: Florence
authors.initials: F
authors.lastname: Menegaux
authors.affiliation: 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.
authors.forename: Sabine
authors.initials: S
authors.lastname: Plancoulaine
authors.affiliation: 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.
authors.forename: Pierre
authors.initials: P
authors.lastname: Laurent-Puig
authors.affiliation: 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.
authors.forename: Claire
authors.initials: C
authors.lastname: Mulot
authors.affiliation: 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.
authors.forename: Emilie
authors.initials: E
authors.lastname: Cordina-Duverger
authors.affiliation: 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.
authors.forename: Marie
authors.initials: M
authors.lastname: Sanchez
authors.affiliation: 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.
authors.forename: Patrick
authors.initials: P
authors.lastname: Arveux
authors.affiliation: 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.
authors.forename: Pierre
authors.initials: P
authors.lastname: Kerbrat
authors.affiliation: 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.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Richardson
authors.affiliation: 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.
authors.forename: Pascal
authors.initials: P
authors.lastname: Guénel
mesh_terms: D000328:Adult; D000368:Aged; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D056926:CLOCK Proteins / Q000235:genetics; D016022:Case-Control Studies; D057906:Circadian Clocks / Q000235:genetics*; D005260:Female; D005602:France / Q000453:epidemiology; D059647:Gene-Environment Interaction; D006801:Humans; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause / Q000235:genetics; D012306:Risk; D014937:Work
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D009419:Nerve Tissue Proteins; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; C104264:NPAS2 protein, human; C539738:RORA protein, human; C538943:CLOCK protein, human
keywords: breast cancer; case–control study; circadian rhythm; nightwork