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Université Paris-Sud UMRS 1018, Villejuif, France
Biostatistical Unit MRC, Cambridge, UK
School of Mathematics and Physics The University of Queensland, St Lucia, Queensland, Australia
Inserm CESP Center for Research in Epidemiology and Population Health, U1018, Epidemiology of Diabetes, Obesity and Chronic Kidney Disease Over Lifecourse, Villejuif, France
Université Paris Descartes INSERM UMR-S775 EPIGENETEC, Paris, France
Département d'informatique médicale Center Georges-François Leclerc, Dijon, France
Center Eugène Marquis Rennes, France
Inserm CESP Center for Research in Epidemiology and Population Health, U1018, Environmental Epidemiology of Cancer, Villejuif, France
Université Paris-Sud UMRS 1018, Villejuif, France
Biostatistical Unit MRC, Cambridge, UK
School of Mathematics and Physics The University of Queensland, St Lucia, Queensland, Australia
Inserm CESP Center for Research in Epidemiology and Population Health, U1018, Epidemiology of Diabetes, Obesity and Chronic Kidney Disease Over Lifecourse, Villejuif, France
Université Paris Descartes INSERM UMR-S775 EPIGENETEC, Paris, France
Département d'informatique médicale Center Georges-François Leclerc, Dijon, France
Center Eugène Marquis Rennes, France
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Université Paris-Sud UMRS 1018, Villejuif, France
Biostatistical Unit MRC, Cambridge, UK
School of Mathematics and Physics The University of Queensland, St Lucia, Queensland, Australia
Inserm CESP Center for Research in Epidemiology and Population Health, U1018, Epidemiology of Diabetes, Obesity and Chronic Kidney Disease Over Lifecourse, Villejuif, France
Université Paris Descartes INSERM UMR-S775 EPIGENETEC, Paris, France
Département d'informatique médicale Center Georges-François Leclerc, Dijon, France
Center Eugène Marquis Rennes, France
Inserm CESP Center for Research in Epidemiology and Population Health, U1018, Environmental Epidemiology of Cancer, Villejuif, France
Université Paris-Sud UMRS 1018, Villejuif, France
Biostatistical Unit MRC, Cambridge, UK
School of Mathematics and Physics The University of Queensland, St Lucia, Queensland, Australia
Inserm CESP Center for Research in Epidemiology and Population Health, U1018, Epidemiology of Diabetes, Obesity and Chronic Kidney Disease Over Lifecourse, Villejuif, France
Université Paris Descartes INSERM UMR-S775 EPIGENETEC, Paris, France
Département d'informatique médicale Center Georges-François Leclerc, Dijon, France
Center Eugène Marquis Rennes, France
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Université Paris-Sud UMRS 1018, Villejuif, France
Biostatistical Unit MRC, Cambridge, UK
School of Mathematics and Physics The University of Queensland, St Lucia, Queensland, Australia
Inserm CESP Center for Research in Epidemiology and Population Health, U1018, Epidemiology of Diabetes, Obesity and Chronic Kidney Disease Over Lifecourse, Villejuif, France
Université Paris Descartes INSERM UMR-S775 EPIGENETEC, Paris, France
Département d'informatique médicale Center Georges-François Leclerc, Dijon, France
Center Eugène Marquis Rennes, France
Inserm CESP Center for Research in Epidemiology and Population Health, U1018, Environmental Epidemiology of Cancer, Villejuif, France
Université Paris-Sud UMRS 1018, Villejuif, France
Biostatistical Unit MRC, Cambridge, UK
School of Mathematics and Physics The University of Queensland, St Lucia, Queensland, Australia
Inserm CESP Center for Research in Epidemiology and Population Health, U1018, Epidemiology of Diabetes, Obesity and Chronic Kidney Disease Over Lifecourse, Villejuif, France
Université Paris Descartes INSERM UMR-S775 EPIGENETEC, Paris, France
Département d'informatique médicale Center Georges-François Leclerc, Dijon, France
Center Eugène Marquis Rennes, France
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Université Paris-Sud UMRS 1018, Villejuif, France
Biostatistical Unit MRC, Cambridge, UK
School of Mathematics and Physics The University of Queensland, St Lucia, Queensland, Australia
Inserm CESP Center for Research in Epidemiology and Population Health, U1018, Epidemiology of Diabetes, Obesity and Chronic Kidney Disease Over Lifecourse, Villejuif, France
Université Paris Descartes INSERM UMR-S775 EPIGENETEC, Paris, France
Département d'informatique médicale Center Georges-François Leclerc, Dijon, France
Center Eugène Marquis Rennes, France
Inserm CESP Center for Research in Epidemiology and Population Health, U1018, Environmental Epidemiology of Cancer, Villejuif, France
Université Paris-Sud UMRS 1018, Villejuif, France
Biostatistical Unit MRC, Cambridge, UK
School of Mathematics and Physics The University of Queensland, St Lucia, Queensland, Australia
Inserm CESP Center for Research in Epidemiology and Population Health, U1018, Epidemiology of Diabetes, Obesity and Chronic Kidney Disease Over Lifecourse, Villejuif, France
Université Paris Descartes INSERM UMR-S775 EPIGENETEC, Paris, France
Département d'informatique médicale Center Georges-François Leclerc, Dijon, France
Center Eugène Marquis Rennes, France
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Université Paris-Sud UMRS 1018, Villejuif, France
Biostatistical Unit MRC, Cambridge, UK
School of Mathematics and Physics The University of Queensland, St Lucia, Queensland, Australia
Inserm CESP Center for Research in Epidemiology and Population Health, U1018, Epidemiology of Diabetes, Obesity and Chronic Kidney Disease Over Lifecourse, Villejuif, France
Université Paris Descartes INSERM UMR-S775 EPIGENETEC, Paris, France
Département d'informatique médicale Center Georges-François Leclerc, Dijon, France
Center Eugène Marquis Rennes, France
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Université Paris-Sud UMRS 1018, Villejuif, France
Biostatistical Unit MRC, Cambridge, UK
School of Mathematics and Physics The University of Queensland, St Lucia, Queensland, Australia
Inserm CESP Center for Research in Epidemiology and Population Health, U1018, Epidemiology of Diabetes, Obesity and Chronic Kidney Disease Over Lifecourse, Villejuif, France
Université Paris Descartes INSERM UMR-S775 EPIGENETEC, Paris, France
Département d'informatique médicale Center Georges-François Leclerc, Dijon, France
Center Eugène Marquis Rennes, France
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Université Paris-Sud UMRS 1018, Villejuif, France
Biostatistical Unit MRC, Cambridge, UK
School of Mathematics and Physics The University of Queensland, St Lucia, Queensland, Australia
Inserm CESP Center for Research in Epidemiology and Population Health, U1018, Epidemiology of Diabetes, Obesity and Chronic Kidney Disease Over Lifecourse, Villejuif, France
Université Paris Descartes INSERM UMR-S775 EPIGENETEC, Paris, France
Département d'informatique médicale Center Georges-François Leclerc, Dijon, France
Center Eugène Marquis Rennes, France
Inserm CESP Center for Research in Epidemiology and Population Health, U1018, Environmental Epidemiology of Cancer, Villejuif, France
Université Paris-Sud UMRS 1018, Villejuif, France
Biostatistical Unit MRC, Cambridge, UK
School of Mathematics and Physics The University of Queensland, St Lucia, Queensland, Australia
Inserm CESP Center for Research in Epidemiology and Population Health, U1018, Epidemiology of Diabetes, Obesity and Chronic Kidney Disease Over Lifecourse, Villejuif, France
Université Paris Descartes INSERM UMR-S775 EPIGENETEC, Paris, France
Département d'informatique médicale Center Georges-François Leclerc, Dijon, France
Center Eugène Marquis Rennes, France
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Université Paris-Sud UMRS 1018, Villejuif, France
Biostatistical Unit MRC, Cambridge, UK
School of Mathematics and Physics The University of Queensland, St Lucia, Queensland, Australia
Inserm CESP Center for Research in Epidemiology and Population Health, U1018, Epidemiology of Diabetes, Obesity and Chronic Kidney Disease Over Lifecourse, Villejuif, France
Université Paris Descartes INSERM UMR-S775 EPIGENETEC, Paris, France
Département d'informatique médicale Center Georges-François Leclerc, Dijon, France
Center Eugène Marquis Rennes, France
Inserm CESP Center for Research in Epidemiology and Population Health, U1018, Environmental Epidemiology of Cancer, Villejuif, France
Université Paris-Sud UMRS 1018, Villejuif, France
Biostatistical Unit MRC, Cambridge, UK
School of Mathematics and Physics The University of Queensland, St Lucia, Queensland, Australia
Inserm CESP Center for Research in Epidemiology and Population Health, U1018, Epidemiology of Diabetes, Obesity and Chronic Kidney Disease Over Lifecourse, Villejuif, France
Université Paris Descartes INSERM UMR-S775 EPIGENETEC, Paris, France
Département d'informatique médicale Center Georges-François Leclerc, Dijon, France
Center Eugène Marquis Rennes, France
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Université Paris-Sud UMRS 1018, Villejuif, France
Biostatistical Unit MRC, Cambridge, UK
School of Mathematics and Physics The University of Queensland, St Lucia, Queensland, Australia
Inserm CESP Center for Research in Epidemiology and Population Health, U1018, Epidemiology of Diabetes, Obesity and Chronic Kidney Disease Over Lifecourse, Villejuif, France
Université Paris Descartes INSERM UMR-S775 EPIGENETEC, Paris, France
Département d'informatique médicale Center Georges-François Leclerc, Dijon, France
Center Eugène Marquis Rennes, France
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Université Paris-Sud UMRS 1018, Villejuif, France
Biostatistical Unit MRC, Cambridge, UK
School of Mathematics and Physics The University of Queensland, St Lucia, Queensland, Australia
Inserm CESP Center for Research in Epidemiology and Population Health, U1018, Epidemiology of Diabetes, Obesity and Chronic Kidney Disease Over Lifecourse, Villejuif, France
Université Paris Descartes INSERM UMR-S775 EPIGENETEC, Paris, France
Département d'informatique médicale Center Georges-François Leclerc, Dijon, France
Center Eugène Marquis Rennes, France
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Université Paris-Sud UMRS 1018, Villejuif, France
Biostatistical Unit MRC, Cambridge, UK
School of Mathematics and Physics The University of Queensland, St Lucia, Queensland, Australia
Inserm CESP Center for Research in Epidemiology and Population Health, U1018, Epidemiology of Diabetes, Obesity and Chronic Kidney Disease Over Lifecourse, Villejuif, France
Université Paris Descartes INSERM UMR-S775 EPIGENETEC, Paris, France
Département d'informatique médicale Center Georges-François Leclerc, Dijon, France
Center Eugène Marquis Rennes, France
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Université Paris-Sud UMRS 1018, Villejuif, France
Biostatistical Unit MRC, Cambridge, UK
School of Mathematics and Physics The University of Queensland, St Lucia, Queensland, Australia
Inserm CESP Center for Research in Epidemiology and Population Health, U1018, Epidemiology of Diabetes, Obesity and Chronic Kidney Disease Over Lifecourse, Villejuif, France
Université Paris Descartes INSERM UMR-S775 EPIGENETEC, Paris, France
Département d'informatique médicale Center Georges-François Leclerc, Dijon, France
Center Eugène Marquis Rennes, France
Inserm CESP Center for Research in Epidemiology and Population Health, U1018, Environmental Epidemiology of Cancer, Villejuif, France
Université Paris-Sud UMRS 1018, Villejuif, France
Biostatistical Unit MRC, Cambridge, UK
School of Mathematics and Physics The University of Queensland, St Lucia, Queensland, Australia
Inserm CESP Center for Research in Epidemiology and Population Health, U1018, Epidemiology of Diabetes, Obesity and Chronic Kidney Disease Over Lifecourse, Villejuif, France
Université Paris Descartes INSERM UMR-S775 EPIGENETEC, Paris, France
Département d'informatique médicale Center Georges-François Leclerc, Dijon, France
Center Eugène Marquis Rennes, France
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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.
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Division of Cancer Epidemiology, PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Foundation for Quality and Efficiency in Health Care (IQWIG), Human Genetics, Department of Public Health and Primary Care, INSERM (National Institute of Health and Medical Research), Unité Mixte de Recherche Scientifique (UMRS) 1018, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute for Occupational Medicine and Maritime Medicine, Department of Internal Medicine, Institute of Pathology, Molecular Genetics of Breast Cancer, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Cancer Epidemiology Centre, Centre for Molecular, Department of Pathology, Division of Cancer Epidemiology and Genetics, Department of Cancer Epidemiology and Prevention, Department of Medical Epidemiology and Biostatistics, Department of Health Sciences Research, Samuel Lunenfeld Research Institute, Division of Epidemiology, Ontario Cancer Genetics Network, Laboratory Medicine Program, Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, Queensland Institute of Medical Research, Peter MacCallum Cancer Center, Sections of Epidemiology and Genetics, Department of Laboratory Medicine and Pathology, Ontario Cancer Genetics Network, Department of Molecular Genetics, Division of Genetics and Epidemiology, Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, Department of Oncology, Department of Obstetrics and Gynecology, Department of Biostatistics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany
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Division of Cancer Epidemiology, PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Foundation for Quality and Efficiency in Health Care (IQWIG), Human Genetics, Department of Public Health and Primary Care, INSERM (National Institute of Health and Medical Research), Unité Mixte de Recherche Scientifique (UMRS) 1018, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute for Occupational Medicine and Maritime Medicine, Department of Internal Medicine, Institute of Pathology, Molecular Genetics of Breast Cancer, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Cancer Epidemiology Centre, Centre for Molecular, Department of Pathology, Division of Cancer Epidemiology and Genetics, Department of Cancer Epidemiology and Prevention, Department of Medical Epidemiology and Biostatistics, Department of Health Sciences Research, Samuel Lunenfeld Research Institute, Division of Epidemiology, Ontario Cancer Genetics Network, Laboratory Medicine Program, Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, Queensland Institute of Medical Research, Peter MacCallum Cancer Center, Sections of Epidemiology and Genetics, Department of Laboratory Medicine and Pathology, Ontario Cancer Genetics Network, Department of Molecular Genetics, Division of Genetics and Epidemiology, Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, Department of Oncology, Department of Obstetrics and Gynecology, Department of Biostatistics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany
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Division of Cancer Epidemiology, PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Foundation for Quality and Efficiency in Health Care (IQWIG), Human Genetics, Department of Public Health and Primary Care, INSERM (National Institute of Health and Medical Research), Unité Mixte de Recherche Scientifique (UMRS) 1018, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute for Occupational Medicine and Maritime Medicine, Department of Internal Medicine, Institute of Pathology, Molecular Genetics of Breast Cancer, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Cancer Epidemiology Centre, Centre for Molecular, Department of Pathology, Division of Cancer Epidemiology and Genetics, Department of Cancer Epidemiology and Prevention, Department of Medical Epidemiology and Biostatistics, Department of Health Sciences Research, Samuel Lunenfeld Research Institute, Division of Epidemiology, Ontario Cancer Genetics Network, Laboratory Medicine Program, Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, Queensland Institute of Medical Research, Peter MacCallum Cancer Center, Sections of Epidemiology and Genetics, Department of Laboratory Medicine and Pathology, Ontario Cancer Genetics Network, Department of Molecular Genetics, Division of Genetics and Epidemiology, Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, Department of Oncology, Department of Obstetrics and Gynecology, Department of Biostatistics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany
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Division of Cancer Epidemiology, PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Foundation for Quality and Efficiency in Health Care (IQWIG), Human Genetics, Department of Public Health and Primary Care, INSERM (National Institute of Health and Medical Research), Unité Mixte de Recherche Scientifique (UMRS) 1018, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute for Occupational Medicine and Maritime Medicine, Department of Internal Medicine, Institute of Pathology, Molecular Genetics of Breast Cancer, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Cancer Epidemiology Centre, Centre for Molecular, Department of Pathology, Division of Cancer Epidemiology and Genetics, Department of Cancer Epidemiology and Prevention, Department of Medical Epidemiology and Biostatistics, Department of Health Sciences Research, Samuel Lunenfeld Research Institute, Division of Epidemiology, Ontario Cancer Genetics Network, Laboratory Medicine Program, Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, Queensland Institute of Medical Research, Peter MacCallum Cancer Center, Sections of Epidemiology and Genetics, Department of Laboratory Medicine and Pathology, Ontario Cancer Genetics Network, Department of Molecular Genetics, Division of Genetics and Epidemiology, Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, Department of Oncology, Department of Obstetrics and Gynecology, Department of Biostatistics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany
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Division of Cancer Epidemiology, PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Foundation for Quality and Efficiency in Health Care (IQWIG), Human Genetics, Department of Public Health and Primary Care, INSERM (National Institute of Health and Medical Research), Unité Mixte de Recherche Scientifique (UMRS) 1018, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute for Occupational Medicine and Maritime Medicine, Department of Internal Medicine, Institute of Pathology, Molecular Genetics of Breast Cancer, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Cancer Epidemiology Centre, Centre for Molecular, Department of Pathology, Division of Cancer Epidemiology and Genetics, Department of Cancer Epidemiology and Prevention, Department of Medical Epidemiology and Biostatistics, Department of Health Sciences Research, Samuel Lunenfeld Research Institute, Division of Epidemiology, Ontario Cancer Genetics Network, Laboratory Medicine Program, Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, Queensland Institute of Medical Research, Peter MacCallum Cancer Center, Sections of Epidemiology and Genetics, Department of Laboratory Medicine and Pathology, Ontario Cancer Genetics Network, Department of Molecular Genetics, Division of Genetics and Epidemiology, Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, Department of Oncology, Department of Obstetrics and Gynecology, Department of Biostatistics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany
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Division of Cancer Epidemiology, PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Foundation for Quality and Efficiency in Health Care (IQWIG), Human Genetics, Department of Public Health and Primary Care, INSERM (National Institute of Health and Medical Research), Unité Mixte de Recherche Scientifique (UMRS) 1018, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute for Occupational Medicine and Maritime Medicine, Department of Internal Medicine, Institute of Pathology, Molecular Genetics of Breast Cancer, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Cancer Epidemiology Centre, Centre for Molecular, Department of Pathology, Division of Cancer Epidemiology and Genetics, Department of Cancer Epidemiology and Prevention, Department of Medical Epidemiology and Biostatistics, Department of Health Sciences Research, Samuel Lunenfeld Research Institute, Division of Epidemiology, Ontario Cancer Genetics Network, Laboratory Medicine Program, Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, Queensland Institute of Medical Research, Peter MacCallum Cancer Center, Sections of Epidemiology and Genetics, Department of Laboratory Medicine and Pathology, Ontario Cancer Genetics Network, Department of Molecular Genetics, Division of Genetics and Epidemiology, Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, Department of Oncology, Department of Obstetrics and Gynecology, Department of Biostatistics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany
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Division of Cancer Epidemiology, PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Foundation for Quality and Efficiency in Health Care (IQWIG), Human Genetics, Department of Public Health and Primary Care, INSERM (National Institute of Health and Medical Research), Unité Mixte de Recherche Scientifique (UMRS) 1018, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute for Occupational Medicine and Maritime Medicine, Department of Internal Medicine, Institute of Pathology, Molecular Genetics of Breast Cancer, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Cancer Epidemiology Centre, Centre for Molecular, Department of Pathology, Division of Cancer Epidemiology and Genetics, Department of Cancer Epidemiology and Prevention, Department of Medical Epidemiology and Biostatistics, Department of Health Sciences Research, Samuel Lunenfeld Research Institute, Division of Epidemiology, Ontario Cancer Genetics Network, Laboratory Medicine Program, Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, Queensland Institute of Medical Research, Peter MacCallum Cancer Center, Sections of Epidemiology and Genetics, Department of Laboratory Medicine and Pathology, Ontario Cancer Genetics Network, Department of Molecular Genetics, Division of Genetics and Epidemiology, Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, Department of Oncology, Department of Obstetrics and Gynecology, Department of Biostatistics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany
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Division of Cancer Epidemiology, PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Foundation for Quality and Efficiency in Health Care (IQWIG), Human Genetics, Department of Public Health and Primary Care, INSERM (National Institute of Health and Medical Research), Unité Mixte de Recherche Scientifique (UMRS) 1018, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute for Occupational Medicine and Maritime Medicine, Department of Internal Medicine, Institute of Pathology, Molecular Genetics of Breast Cancer, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Cancer Epidemiology Centre, Centre for Molecular, Department of Pathology, Division of Cancer Epidemiology and Genetics, Department of Cancer Epidemiology and Prevention, Department of Medical Epidemiology and Biostatistics, Department of Health Sciences Research, Samuel Lunenfeld Research Institute, Division of Epidemiology, Ontario Cancer Genetics Network, Laboratory Medicine Program, Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, Queensland Institute of Medical Research, Peter MacCallum Cancer Center, Sections of Epidemiology and Genetics, Department of Laboratory Medicine and Pathology, Ontario Cancer Genetics Network, Department of Molecular Genetics, Division of Genetics and Epidemiology, Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, Department of Oncology, Department of Obstetrics and Gynecology, Department of Biostatistics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany
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Division of Cancer Epidemiology, PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Foundation for Quality and Efficiency in Health Care (IQWIG), Human Genetics, Department of Public Health and Primary Care, INSERM (National Institute of Health and Medical Research), Unité Mixte de Recherche Scientifique (UMRS) 1018, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute for Occupational Medicine and Maritime Medicine, Department of Internal Medicine, Institute of Pathology, Molecular Genetics of Breast Cancer, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Cancer Epidemiology Centre, Centre for Molecular, Department of Pathology, Division of Cancer Epidemiology and Genetics, Department of Cancer Epidemiology and Prevention, Department of Medical Epidemiology and Biostatistics, Department of Health Sciences Research, Samuel Lunenfeld Research Institute, Division of Epidemiology, Ontario Cancer Genetics Network, Laboratory Medicine Program, Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, Queensland Institute of Medical Research, Peter MacCallum Cancer Center, Sections of Epidemiology and Genetics, Department of Laboratory Medicine and Pathology, Ontario Cancer Genetics Network, Department of Molecular Genetics, Division of Genetics and Epidemiology, Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, Department of Oncology, Department of Obstetrics and Gynecology, Department of Biostatistics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany
Division of Cancer Epidemiology, PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Foundation for Quality and Efficiency in Health Care (IQWIG), Human Genetics, Department of Public Health and Primary Care, INSERM (National Institute of Health and Medical Research), Unité Mixte de Recherche Scientifique (UMRS) 1018, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute for Occupational Medicine and Maritime Medicine, Department of Internal Medicine, Institute of Pathology, Molecular Genetics of Breast Cancer, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Cancer Epidemiology Centre, Centre for Molecular, Department of Pathology, Division of Cancer Epidemiology and Genetics, Department of Cancer Epidemiology and Prevention, Department of Medical Epidemiology and Biostatistics, Department of Health Sciences Research, Samuel Lunenfeld Research Institute, Division of Epidemiology, Ontario Cancer Genetics Network, Laboratory Medicine Program, Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, Queensland Institute of Medical Research, Peter MacCallum Cancer Center, Sections of Epidemiology and Genetics, Department of Laboratory Medicine and Pathology, Ontario Cancer Genetics Network, Department of Molecular Genetics, Division of Genetics and Epidemiology, Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, Department of Oncology, Department of Obstetrics and Gynecology, Department of Biostatistics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany
Division of Cancer Epidemiology, PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Foundation for Quality and Efficiency in Health Care (IQWIG), Human Genetics, Department of Public Health and Primary Care, INSERM (National Institute of Health and Medical Research), Unité Mixte de Recherche Scientifique (UMRS) 1018, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute for Occupational Medicine and Maritime Medicine, Department of Internal Medicine, Institute of Pathology, Molecular Genetics of Breast Cancer, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Cancer Epidemiology Centre, Centre for Molecular, Department of Pathology, Division of Cancer Epidemiology and Genetics, Department of Cancer Epidemiology and Prevention, Department of Medical Epidemiology and Biostatistics, Department of Health Sciences Research, Samuel Lunenfeld Research Institute, Division of Epidemiology, Ontario Cancer Genetics Network, Laboratory Medicine Program, Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, Queensland Institute of Medical Research, Peter MacCallum Cancer Center, Sections of Epidemiology and Genetics, Department of Laboratory Medicine and Pathology, Ontario Cancer Genetics Network, Department of Molecular Genetics, Division of Genetics and Epidemiology, Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, Department of Oncology, Department of Obstetrics and Gynecology, Department of Biostatistics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany
Division of Cancer Epidemiology, PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Foundation for Quality and Efficiency in Health Care (IQWIG), Human Genetics, Department of Public Health and Primary Care, INSERM (National Institute of Health and Medical Research), Unité Mixte de Recherche Scientifique (UMRS) 1018, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute for Occupational Medicine and Maritime Medicine, Department of Internal Medicine, Institute of Pathology, Molecular Genetics of Breast Cancer, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Cancer Epidemiology Centre, Centre for Molecular, Department of Pathology, Division of Cancer Epidemiology and Genetics, Department of Cancer Epidemiology and Prevention, Department of Medical Epidemiology and Biostatistics, Department of Health Sciences Research, Samuel Lunenfeld Research Institute, Division of Epidemiology, Ontario Cancer Genetics Network, Laboratory Medicine Program, Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, Queensland Institute of Medical Research, Peter MacCallum Cancer Center, Sections of Epidemiology and Genetics, Department of Laboratory Medicine and Pathology, Ontario Cancer Genetics Network, Department of Molecular Genetics, Division of Genetics and Epidemiology, Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, Department of Oncology, Department of Obstetrics and Gynecology, Department of Biostatistics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany
Division of Cancer Epidemiology, PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Foundation for Quality and Efficiency in Health Care (IQWIG), Human Genetics, Department of Public Health and Primary Care, INSERM (National Institute of Health and Medical Research), Unité Mixte de Recherche Scientifique (UMRS) 1018, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute for Occupational Medicine and Maritime Medicine, Department of Internal Medicine, Institute of Pathology, Molecular Genetics of Breast Cancer, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Cancer Epidemiology Centre, Centre for Molecular, Department of Pathology, Division of Cancer Epidemiology and Genetics, Department of Cancer Epidemiology and Prevention, Department of Medical Epidemiology and Biostatistics, Department of Health Sciences Research, Samuel Lunenfeld Research Institute, Division of Epidemiology, Ontario Cancer Genetics Network, Laboratory Medicine Program, Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, Queensland Institute of Medical Research, Peter MacCallum Cancer Center, Sections of Epidemiology and Genetics, Department of Laboratory Medicine and Pathology, Ontario Cancer Genetics Network, Department of Molecular Genetics, Division of Genetics and Epidemiology, Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, Department of Oncology, Department of Obstetrics and Gynecology, Department of Biostatistics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany
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Division of Cancer Epidemiology, PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Foundation for Quality and Efficiency in Health Care (IQWIG), Human Genetics, Department of Public Health and Primary Care, INSERM (National Institute of Health and Medical Research), Unité Mixte de Recherche Scientifique (UMRS) 1018, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute for Occupational Medicine and Maritime Medicine, Department of Internal Medicine, Institute of Pathology, Molecular Genetics of Breast Cancer, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Cancer Epidemiology Centre, Centre for Molecular, Department of Pathology, Division of Cancer Epidemiology and Genetics, Department of Cancer Epidemiology and Prevention, Department of Medical Epidemiology and Biostatistics, Department of Health Sciences Research, Samuel Lunenfeld Research Institute, Division of Epidemiology, Ontario Cancer Genetics Network, Laboratory Medicine Program, Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, Queensland Institute of Medical Research, Peter MacCallum Cancer Center, Sections of Epidemiology and Genetics, Department of Laboratory Medicine and Pathology, Ontario Cancer Genetics Network, Department of Molecular Genetics, Division of Genetics and Epidemiology, Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, Department of Oncology, Department of Obstetrics and Gynecology, Department of Biostatistics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany
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Division of Cancer Epidemiology, PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Foundation for Quality and Efficiency in Health Care (IQWIG), Human Genetics, Department of Public Health and Primary Care, INSERM (National Institute of Health and Medical Research), Unité Mixte de Recherche Scientifique (UMRS) 1018, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute for Occupational Medicine and Maritime Medicine, Department of Internal Medicine, Institute of Pathology, Molecular Genetics of Breast Cancer, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Cancer Epidemiology Centre, Centre for Molecular, Department of Pathology, Division of Cancer Epidemiology and Genetics, Department of Cancer Epidemiology and Prevention, Department of Medical Epidemiology and Biostatistics, Department of Health Sciences Research, Samuel Lunenfeld Research Institute, Division of Epidemiology, Ontario Cancer Genetics Network, Laboratory Medicine Program, Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, Queensland Institute of Medical Research, Peter MacCallum Cancer Center, Sections of Epidemiology and Genetics, Department of Laboratory Medicine and Pathology, Ontario Cancer Genetics Network, Department of Molecular Genetics, Division of Genetics and Epidemiology, Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, Department of Oncology, Department of Obstetrics and Gynecology, Department of Biostatistics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany
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Division of Cancer Epidemiology, PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Foundation for Quality and Efficiency in Health Care (IQWIG), Human Genetics, Department of Public Health and Primary Care, INSERM (National Institute of Health and Medical Research), Unité Mixte de Recherche Scientifique (UMRS) 1018, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute for Occupational Medicine and Maritime Medicine, Department of Internal Medicine, Institute of Pathology, Molecular Genetics of Breast Cancer, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Cancer Epidemiology Centre, Centre for Molecular, Department of Pathology, Division of Cancer Epidemiology and Genetics, Department of Cancer Epidemiology and Prevention, Department of Medical Epidemiology and Biostatistics, Department of Health Sciences Research, Samuel Lunenfeld Research Institute, Division of Epidemiology, Ontario Cancer Genetics Network, Laboratory Medicine Program, Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, Queensland Institute of Medical Research, Peter MacCallum Cancer Center, Sections of Epidemiology and Genetics, Department of Laboratory Medicine and Pathology, Ontario Cancer Genetics Network, Department of Molecular Genetics, Division of Genetics and Epidemiology, Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, Department of Oncology, Department of Obstetrics and Gynecology, Department of Biostatistics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany
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Division of Cancer Epidemiology, PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Foundation for Quality and Efficiency in Health Care (IQWIG), Human Genetics, Department of Public Health and Primary Care, INSERM (National Institute of Health and Medical Research), Unité Mixte de Recherche Scientifique (UMRS) 1018, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute for Occupational Medicine and Maritime Medicine, Department of Internal Medicine, Institute of Pathology, Molecular Genetics of Breast Cancer, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Cancer Epidemiology Centre, Centre for Molecular, Department of Pathology, Division of Cancer Epidemiology and Genetics, Department of Cancer Epidemiology and Prevention, Department of Medical Epidemiology and Biostatistics, Department of Health Sciences Research, Samuel Lunenfeld Research Institute, Division of Epidemiology, Ontario Cancer Genetics Network, Laboratory Medicine Program, Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, Queensland Institute of Medical Research, Peter MacCallum Cancer Center, Sections of Epidemiology and Genetics, Department of Laboratory Medicine and Pathology, Ontario Cancer Genetics Network, Department of Molecular Genetics, Division of Genetics and Epidemiology, Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, Department of Oncology, Department of Obstetrics and Gynecology, Department of Biostatistics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany
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Division of Cancer Epidemiology, PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Foundation for Quality and Efficiency in Health Care (IQWIG), Human Genetics, Department of Public Health and Primary Care, INSERM (National Institute of Health and Medical Research), Unité Mixte de Recherche Scientifique (UMRS) 1018, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute for Occupational Medicine and Maritime Medicine, Department of Internal Medicine, Institute of Pathology, Molecular Genetics of Breast Cancer, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Cancer Epidemiology Centre, Centre for Molecular, Department of Pathology, Division of Cancer Epidemiology and Genetics, Department of Cancer Epidemiology and Prevention, Department of Medical Epidemiology and Biostatistics, Department of Health Sciences Research, Samuel Lunenfeld Research Institute, Division of Epidemiology, Ontario Cancer Genetics Network, Laboratory Medicine Program, Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, Queensland Institute of Medical Research, Peter MacCallum Cancer Center, Sections of Epidemiology and Genetics, Department of Laboratory Medicine and Pathology, Ontario Cancer Genetics Network, Department of Molecular Genetics, Division of Genetics and Epidemiology, Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, Department of Oncology, Department of Obstetrics and Gynecology, Department of Biostatistics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany
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Division of Cancer Epidemiology, PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Foundation for Quality and Efficiency in Health Care (IQWIG), Human Genetics, Department of Public Health and Primary Care, INSERM (National Institute of Health and Medical Research), Unité Mixte de Recherche Scientifique (UMRS) 1018, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute for Occupational Medicine and Maritime Medicine, Department of Internal Medicine, Institute of Pathology, Molecular Genetics of Breast Cancer, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Cancer Epidemiology Centre, Centre for Molecular, Department of Pathology, Division of Cancer Epidemiology and Genetics, Department of Cancer Epidemiology and Prevention, Department of Medical Epidemiology and Biostatistics, Department of Health Sciences Research, Samuel Lunenfeld Research Institute, Division of Epidemiology, Ontario Cancer Genetics Network, Laboratory Medicine Program, Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, Queensland Institute of Medical Research, Peter MacCallum Cancer Center, Sections of Epidemiology and Genetics, Department of Laboratory Medicine and Pathology, Ontario Cancer Genetics Network, Department of Molecular Genetics, Division of Genetics and Epidemiology, Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, Department of Oncology, Department of Obstetrics and Gynecology, Department of Biostatistics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany
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Division of Cancer Epidemiology, PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Foundation for Quality and Efficiency in Health Care (IQWIG), Human Genetics, Department of Public Health and Primary Care, INSERM (National Institute of Health and Medical Research), Unité Mixte de Recherche Scientifique (UMRS) 1018, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute for Occupational Medicine and Maritime Medicine, Department of Internal Medicine, Institute of Pathology, Molecular Genetics of Breast Cancer, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Cancer Epidemiology Centre, Centre for Molecular, Department of Pathology, Division of Cancer Epidemiology and Genetics, Department of Cancer Epidemiology and Prevention, Department of Medical Epidemiology and Biostatistics, Department of Health Sciences Research, Samuel Lunenfeld Research Institute, Division of Epidemiology, Ontario Cancer Genetics Network, Laboratory Medicine Program, Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, Queensland Institute of Medical Research, Peter MacCallum Cancer Center, Sections of Epidemiology and Genetics, Department of Laboratory Medicine and Pathology, Ontario Cancer Genetics Network, Department of Molecular Genetics, Division of Genetics and Epidemiology, Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, Department of Oncology, Department of Obstetrics and Gynecology, Department of Biostatistics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany
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Division of Cancer Epidemiology, PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Foundation for Quality and Efficiency in Health Care (IQWIG), Human Genetics, Department of Public Health and Primary Care, INSERM (National Institute of Health and Medical Research), Unité Mixte de Recherche Scientifique (UMRS) 1018, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute for Occupational Medicine and Maritime Medicine, Department of Internal Medicine, Institute of Pathology, Molecular Genetics of Breast Cancer, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Cancer Epidemiology Centre, Centre for Molecular, Department of Pathology, Division of Cancer Epidemiology and Genetics, Department of Cancer Epidemiology and Prevention, Department of Medical Epidemiology and Biostatistics, Department of Health Sciences Research, Samuel Lunenfeld Research Institute, Division of Epidemiology, Ontario Cancer Genetics Network, Laboratory Medicine Program, Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, Queensland Institute of Medical Research, Peter MacCallum Cancer Center, Sections of Epidemiology and Genetics, Department of Laboratory Medicine and Pathology, Ontario Cancer Genetics Network, Department of Molecular Genetics, Division of Genetics and Epidemiology, Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, Department of Oncology, Department of Obstetrics and Gynecology, Department of Biostatistics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany
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Division of Cancer Epidemiology, PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Foundation for Quality and Efficiency in Health Care (IQWIG), Human Genetics, Department of Public Health and Primary Care, INSERM (National Institute of Health and Medical Research), Unité Mixte de Recherche Scientifique (UMRS) 1018, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute for Occupational Medicine and Maritime Medicine, Department of Internal Medicine, Institute of Pathology, Molecular Genetics of Breast Cancer, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Cancer Epidemiology Centre, Centre for Molecular, Department of Pathology, Division of Cancer Epidemiology and Genetics, Department of Cancer Epidemiology and Prevention, Department of Medical Epidemiology and Biostatistics, Department of Health Sciences Research, Samuel Lunenfeld Research Institute, Division of Epidemiology, Ontario Cancer Genetics Network, Laboratory Medicine Program, Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, Queensland Institute of Medical Research, Peter MacCallum Cancer Center, Sections of Epidemiology and Genetics, Department of Laboratory Medicine and Pathology, Ontario Cancer Genetics Network, Department of Molecular Genetics, Division of Genetics and Epidemiology, Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, Department of Oncology, Department of Obstetrics and Gynecology, Department of Biostatistics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany
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Division of Cancer Epidemiology, PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Foundation for Quality and Efficiency in Health Care (IQWIG), Human Genetics, Department of Public Health and Primary Care, INSERM (National Institute of Health and Medical Research), Unité Mixte de Recherche Scientifique (UMRS) 1018, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute for Occupational Medicine and Maritime Medicine, Department of Internal Medicine, Institute of Pathology, Molecular Genetics of Breast Cancer, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Cancer Epidemiology Centre, Centre for Molecular, Department of Pathology, Division of Cancer Epidemiology and Genetics, Department of Cancer Epidemiology and Prevention, Department of Medical Epidemiology and Biostatistics, Department of Health Sciences Research, Samuel Lunenfeld Research Institute, Division of Epidemiology, Ontario Cancer Genetics Network, Laboratory Medicine Program, Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, Queensland Institute of Medical Research, Peter MacCallum Cancer Center, Sections of Epidemiology and Genetics, Department of Laboratory Medicine and Pathology, Ontario Cancer Genetics Network, Department of Molecular Genetics, Division of Genetics and Epidemiology, Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, Department of Oncology, Department of Obstetrics and Gynecology, Department of Biostatistics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany
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Division of Cancer Epidemiology, PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Foundation for Quality and Efficiency in Health Care (IQWIG), Human Genetics, Department of Public Health and Primary Care, INSERM (National Institute of Health and Medical Research), Unité Mixte de Recherche Scientifique (UMRS) 1018, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute for Occupational Medicine and Maritime Medicine, Department of Internal Medicine, Institute of Pathology, Molecular Genetics of Breast Cancer, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Cancer Epidemiology Centre, Centre for Molecular, Department of Pathology, Division of Cancer Epidemiology and Genetics, Department of Cancer Epidemiology and Prevention, Department of Medical Epidemiology and Biostatistics, Department of Health Sciences Research, Samuel Lunenfeld Research Institute, Division of Epidemiology, Ontario Cancer Genetics Network, Laboratory Medicine Program, Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, Queensland Institute of Medical Research, Peter MacCallum Cancer Center, Sections of Epidemiology and Genetics, Department of Laboratory Medicine and Pathology, Ontario Cancer Genetics Network, Department of Molecular Genetics, Division of Genetics and Epidemiology, Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, Department of Oncology, Department of Obstetrics and Gynecology, Department of Biostatistics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany
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Division of Cancer Epidemiology, PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Foundation for Quality and Efficiency in Health Care (IQWIG), Human Genetics, Department of Public Health and Primary Care, INSERM (National Institute of Health and Medical Research), Unité Mixte de Recherche Scientifique (UMRS) 1018, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute for Occupational Medicine and Maritime Medicine, Department of Internal Medicine, Institute of Pathology, Molecular Genetics of Breast Cancer, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Cancer Epidemiology Centre, Centre for Molecular, Department of Pathology, Division of Cancer Epidemiology and Genetics, Department of Cancer Epidemiology and Prevention, Department of Medical Epidemiology and Biostatistics, Department of Health Sciences Research, Samuel Lunenfeld Research Institute, Division of Epidemiology, Ontario Cancer Genetics Network, Laboratory Medicine Program, Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, Queensland Institute of Medical Research, Peter MacCallum Cancer Center, Sections of Epidemiology and Genetics, Department of Laboratory Medicine and Pathology, Ontario Cancer Genetics Network, Department of Molecular Genetics, Division of Genetics and Epidemiology, Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, Department of Oncology, Department of Obstetrics and Gynecology, Department of Biostatistics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany
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Division of Cancer Epidemiology, PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Foundation for Quality and Efficiency in Health Care (IQWIG), Human Genetics, Department of Public Health and Primary Care, INSERM (National Institute of Health and Medical Research), Unité Mixte de Recherche Scientifique (UMRS) 1018, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute for Occupational Medicine and Maritime Medicine, Department of Internal Medicine, Institute of Pathology, Molecular Genetics of Breast Cancer, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Cancer Epidemiology Centre, Centre for Molecular, Department of Pathology, Division of Cancer Epidemiology and Genetics, Department of Cancer Epidemiology and Prevention, Department of Medical Epidemiology and Biostatistics, Department of Health Sciences Research, Samuel Lunenfeld Research Institute, Division of Epidemiology, Ontario Cancer Genetics Network, Laboratory Medicine Program, Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, Queensland Institute of Medical Research, Peter MacCallum Cancer Center, Sections of Epidemiology and Genetics, Department of Laboratory Medicine and Pathology, Ontario Cancer Genetics Network, Department of Molecular Genetics, Division of Genetics and Epidemiology, Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, Department of Oncology, Department of Obstetrics and Gynecology, Department of Biostatistics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany
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Division of Cancer Epidemiology, PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Foundation for Quality and Efficiency in Health Care (IQWIG), Human Genetics, Department of Public Health and Primary Care, INSERM (National Institute of Health and Medical Research), Unité Mixte de Recherche Scientifique (UMRS) 1018, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute for Occupational Medicine and Maritime Medicine, Department of Internal Medicine, Institute of Pathology, Molecular Genetics of Breast Cancer, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Cancer Epidemiology Centre, Centre for Molecular, Department of Pathology, Division of Cancer Epidemiology and Genetics, Department of Cancer Epidemiology and Prevention, Department of Medical Epidemiology and Biostatistics, Department of Health Sciences Research, Samuel Lunenfeld Research Institute, Division of Epidemiology, Ontario Cancer Genetics Network, Laboratory Medicine Program, Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, Queensland Institute of Medical Research, Peter MacCallum Cancer Center, Sections of Epidemiology and Genetics, Department of Laboratory Medicine and Pathology, Ontario Cancer Genetics Network, Department of Molecular Genetics, Division of Genetics and Epidemiology, Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, Department of Oncology, Department of Obstetrics and Gynecology, Department of Biostatistics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany
Division of Cancer Epidemiology, PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Foundation for Quality and Efficiency in Health Care (IQWIG), Human Genetics, Department of Public Health and Primary Care, INSERM (National Institute of Health and Medical Research), Unité Mixte de Recherche Scientifique (UMRS) 1018, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute for Occupational Medicine and Maritime Medicine, Department of Internal Medicine, Institute of Pathology, Molecular Genetics of Breast Cancer, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Cancer Epidemiology Centre, Centre for Molecular, Department of Pathology, Division of Cancer Epidemiology and Genetics, Department of Cancer Epidemiology and Prevention, Department of Medical Epidemiology and Biostatistics, Department of Health Sciences Research, Samuel Lunenfeld Research Institute, Division of Epidemiology, Ontario Cancer Genetics Network, Laboratory Medicine Program, Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, Queensland Institute of Medical Research, Peter MacCallum Cancer Center, Sections of Epidemiology and Genetics, Department of Laboratory Medicine and Pathology, Ontario Cancer Genetics Network, Department of Molecular Genetics, Division of Genetics and Epidemiology, Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, Department of Oncology, Department of Obstetrics and Gynecology, Department of Biostatistics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany
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Women using menopausal hormone therapy (MHT) are at increased risk of developing breast cancer (BC). To detect genetic modifiers of the association between current use of MHT and BC risk, we conducted a meta-analysis of four genome-wide case-only studies followed by replication in 11 case–control studies. We used a case-only design to assess interactions between single-nucleotide polymorphisms (SNPs) and current MHT use on risk of overall and lobular BC. The discovery stage included 2920 cases (541 lobular) from four genome-wide association studies. The top 1391 SNPs showing P values for interaction (Pint) <3.0×10−3 were selected for replication using pooled case–control data from 11 studies of the Breast Cancer Association Consortium, including 7689 cases (676 lobular) and 9266 controls. Fixed-effects meta-analysis was used to derive combined Pint. No SNP reached genome-wide significance in either the discovery or combined stage. We observed effect modification of current MHT use on overall BC risk by two SNPs on chr13 near POMP (combined Pint≤8.9×10−6), two SNPs in SLC25A21 (combined Pint≤4.8×10−5), and three SNPs in PLCG2 (combined Pint≤4.5×10−5). The association between lobular BC risk was potentially modified by one SNP in TMEFF2 (combined Pint≤2.7×10−5), one SNP in CD80 (combined Pint≤8.2×10−6), three SNPs on chr17 near TMEM132E (combined Pint≤2.2×10−6), and two SNPs on chr18 near SLC25A52 (combined Pint≤4.6×10−5). In conclusion, polymorphisms in genes related to solute transportation in mitochondria, transmembrane signaling, and immune cell activation are potentially modifying BC risk associated with current use of MHT. These findings warrant replication in independent studies.