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Biomarker Initiative, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge, UK
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Biomarker Initiative, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge, UK
Molecular Diagnostics and Therapeutics Group, University College London, London, UK
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Astra Zeneca, 2 Riverside, Granta Park, Cambridge, UK
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Astra Zeneca, 2 Riverside, Granta Park, Cambridge, UK
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Molecular Diagnostics and Therapeutics Group, University College London, London, UK
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Biomarker Initiative, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge, UK
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Molecular and Computational Diagnostics Group, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge, UK
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University College Hospital at Westmoreland Street, London, UK
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Nuffield Department of Surgical Sciences, John Radcliffe Hospital, Headington, Oxford, UK
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Biomarker Initiative, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge, UK
Molecular Diagnostics and Therapeutics Group, University College London, London, UK
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Due to increased sensitivity, the expression of circulating nucleotides is rapidly gaining popularity in cancer diagnosis. Whole blood mRNA has been used in studies on a number of cancers, most notably two separate studies that used whole blood mRNA to define non-overlapping signatures of prostate cancer that has become castration independent. Prostate cancer is known to rely on androgens for initial growth, and there is increasing evidence on the importance of the androgen axis in advanced disease. Using whole blood mRNA samples from patients with prostate cancer, we have identified the four-gene panel of FAM129A, MME, KRT7 and SOD2 in circulating mRNA that are differentially expressed in a discovery cohort of metastatic samples. Validation of these genes at the mRNA and protein level was undertaken in additional cohorts defined by risk of relapse following surgery and hormone status. All the four genes were downregulated at the mRNA level in the circulation and in primary tissue, but this was not always reflected in tissue protein expression. MME demonstrated significant differences in the hormone cohorts, whereas FAM129A is downregulated at the mRNA level but is raised at the protein level in tumours. Using published ChIP-seq data, we have demonstrated that this may be due to AR binding at the FAM129A and MME loci in multiple cell lines. These data suggest that whole blood mRNA of androgen-regulated genes has the potential to be used for diagnosis and monitoring of prostate cancer.
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Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
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Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
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Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
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Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
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Prostate cancer is the most common cancer in men, resulting in over 10 000 deaths/year in the UK. Sequencing and copy number analysis of primary tumours has revealed heterogeneity within tumours and an absence of recurrent founder mutations, consistent with non-genetic disease initiating events. Using methylation profiling in a series of multi-focal prostate tumours, we identify promoter methylation of the transcription factor HES5 as an early event in prostate tumourigenesis. We confirm that this epigenetic alteration occurs in 86–97% of cases in two independent prostate cancer cohorts (n=49 and n=39 tumour–normal pairs). Treatment of prostate cancer cells with the demethylating agent 5-aza-2′-deoxycytidine increased HES5 expression and downregulated its transcriptional target HES6, consistent with functional silencing of the HES5 gene in prostate cancer. Finally, we identify and test a transcriptional module involving the AR, ERG, HES1 and HES6 and propose a model for the impact of HES5 silencing on tumourigenesis as a starting point for future functional studies.
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Department of Public Health and Primary Care, Department of Genetics and Computational Biology, Wellcome Trust Centre for Human Genetics, Academic Department of Biochemistry, Department of Clinical Genetics, Department of Oncology, Department of Medical Epidemiology and Biostatistics, Department of Medicine, Department of Gynecology and Obstetrics, Institute of Human Genetics, Gynaecology Research Unit, Clinics of Gynaecology and Obstetrics, Department of Gynaecology, Vesalius Research Center, Laboratory for Translational Genetics, Department of Obstetrics and Gynecology, Department of Health Sciences Research, Department of Biostatistics, Department of Obstetrics and Gynecology, Centre for Cancerbiomarkers, Department of Obstetrics and Gynecology, Hunter Medical Research Institute, Centre for Information Based Medicine, School of Biomedical Sciences and Pharmacy, School of Medicine and Public Health, Grupo de investigación Citogenética, Genome Center and Department of Biochemistry and Molecular Medicine, Department of Molecular Medicine and Surgery, Department of Women's and Children's Health, Hunter Area Pathology Service, Centre for Clinical Epidemiology and Biostatistics, Institute of Health and Biomedical Innovation, Centre for Epidemiology and Biostatistics, Peter MacCallum Cancer Center, Division of Genetics and Epidemiology, Division of Breast Cancer Research, Department of Gynecology and Obstetrics, Division of Cancer Epidemiology, Division of Clinical Epidemiology and Aging Research, Division of Preventive Oncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Department of Obstetrics and Gynecology, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Department of Laboratory Medicine and Pathology, Cancer Epidemiology Centre, Department of Epidemiology and Preventive Medicine, Department of Genetics, The K.G. Jebsen Center for Breast Cancer Research, Department of Clinical Molecular Oncology, Department of Oncology, Faculty of Health and Medical Sciences, Department of Clinical Biochemistry, Department of Public Health and Primary Care, MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival (CNC), Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, Cambridge CB1 8RN, UK
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Department of Public Health and Primary Care, Department of Genetics and Computational Biology, Wellcome Trust Centre for Human Genetics, Academic Department of Biochemistry, Department of Clinical Genetics, Department of Oncology, Department of Medical Epidemiology and Biostatistics, Department of Medicine, Department of Gynecology and Obstetrics, Institute of Human Genetics, Gynaecology Research Unit, Clinics of Gynaecology and Obstetrics, Department of Gynaecology, Vesalius Research Center, Laboratory for Translational Genetics, Department of Obstetrics and Gynecology, Department of Health Sciences Research, Department of Biostatistics, Department of Obstetrics and Gynecology, Centre for Cancerbiomarkers, Department of Obstetrics and Gynecology, Hunter Medical Research Institute, Centre for Information Based Medicine, School of Biomedical Sciences and Pharmacy, School of Medicine and Public Health, Grupo de investigación Citogenética, Genome Center and Department of Biochemistry and Molecular Medicine, Department of Molecular Medicine and Surgery, Department of Women's and Children's Health, Hunter Area Pathology Service, Centre for Clinical Epidemiology and Biostatistics, Institute of Health and Biomedical Innovation, Centre for Epidemiology and Biostatistics, Peter MacCallum Cancer Center, Division of Genetics and Epidemiology, Division of Breast Cancer Research, Department of Gynecology and Obstetrics, Division of Cancer Epidemiology, Division of Clinical Epidemiology and Aging Research, Division of Preventive Oncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Department of Obstetrics and Gynecology, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Department of Laboratory Medicine and Pathology, Cancer Epidemiology Centre, Department of Epidemiology and Preventive Medicine, Department of Genetics, The K.G. Jebsen Center for Breast Cancer Research, Department of Clinical Molecular Oncology, Department of Oncology, Faculty of Health and Medical Sciences, Department of Clinical Biochemistry, Department of Public Health and Primary Care, MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival (CNC), Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, Cambridge CB1 8RN, UK
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Department of Public Health and Primary Care, Department of Genetics and Computational Biology, Wellcome Trust Centre for Human Genetics, Academic Department of Biochemistry, Department of Clinical Genetics, Department of Oncology, Department of Medical Epidemiology and Biostatistics, Department of Medicine, Department of Gynecology and Obstetrics, Institute of Human Genetics, Gynaecology Research Unit, Clinics of Gynaecology and Obstetrics, Department of Gynaecology, Vesalius Research Center, Laboratory for Translational Genetics, Department of Obstetrics and Gynecology, Department of Health Sciences Research, Department of Biostatistics, Department of Obstetrics and Gynecology, Centre for Cancerbiomarkers, Department of Obstetrics and Gynecology, Hunter Medical Research Institute, Centre for Information Based Medicine, School of Biomedical Sciences and Pharmacy, School of Medicine and Public Health, Grupo de investigación Citogenética, Genome Center and Department of Biochemistry and Molecular Medicine, Department of Molecular Medicine and Surgery, Department of Women's and Children's Health, Hunter Area Pathology Service, Centre for Clinical Epidemiology and Biostatistics, Institute of Health and Biomedical Innovation, Centre for Epidemiology and Biostatistics, Peter MacCallum Cancer Center, Division of Genetics and Epidemiology, Division of Breast Cancer Research, Department of Gynecology and Obstetrics, Division of Cancer Epidemiology, Division of Clinical Epidemiology and Aging Research, Division of Preventive Oncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Department of Obstetrics and Gynecology, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Department of Laboratory Medicine and Pathology, Cancer Epidemiology Centre, Department of Epidemiology and Preventive Medicine, Department of Genetics, The K.G. Jebsen Center for Breast Cancer Research, Department of Clinical Molecular Oncology, Department of Oncology, Faculty of Health and Medical Sciences, Department of Clinical Biochemistry, Department of Public Health and Primary Care, MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival (CNC), Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, Cambridge CB1 8RN, UK
Department of Public Health and Primary Care, Department of Genetics and Computational Biology, Wellcome Trust Centre for Human Genetics, Academic Department of Biochemistry, Department of Clinical Genetics, Department of Oncology, Department of Medical Epidemiology and Biostatistics, Department of Medicine, Department of Gynecology and Obstetrics, Institute of Human Genetics, Gynaecology Research Unit, Clinics of Gynaecology and Obstetrics, Department of Gynaecology, Vesalius Research Center, Laboratory for Translational Genetics, Department of Obstetrics and Gynecology, Department of Health Sciences Research, Department of Biostatistics, Department of Obstetrics and Gynecology, Centre for Cancerbiomarkers, Department of Obstetrics and Gynecology, Hunter Medical Research Institute, Centre for Information Based Medicine, School of Biomedical Sciences and Pharmacy, School of Medicine and Public Health, Grupo de investigación Citogenética, Genome Center and Department of Biochemistry and Molecular Medicine, Department of Molecular Medicine and Surgery, Department of Women's and Children's Health, Hunter Area Pathology Service, Centre for Clinical Epidemiology and Biostatistics, Institute of Health and Biomedical Innovation, Centre for Epidemiology and Biostatistics, Peter MacCallum Cancer Center, Division of Genetics and Epidemiology, Division of Breast Cancer Research, Department of Gynecology and Obstetrics, Division of Cancer Epidemiology, Division of Clinical Epidemiology and Aging Research, Division of Preventive Oncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Department of Obstetrics and Gynecology, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Department of Laboratory Medicine and Pathology, Cancer Epidemiology Centre, Department of Epidemiology and Preventive Medicine, Department of Genetics, The K.G. Jebsen Center for Breast Cancer Research, Department of Clinical Molecular Oncology, Department of Oncology, Faculty of Health and Medical Sciences, Department of Clinical Biochemistry, Department of Public Health and Primary Care, MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival (CNC), Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, Cambridge CB1 8RN, UK
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Department of Public Health and Primary Care, Department of Genetics and Computational Biology, Wellcome Trust Centre for Human Genetics, Academic Department of Biochemistry, Department of Clinical Genetics, Department of Oncology, Department of Medical Epidemiology and Biostatistics, Department of Medicine, Department of Gynecology and Obstetrics, Institute of Human Genetics, Gynaecology Research Unit, Clinics of Gynaecology and Obstetrics, Department of Gynaecology, Vesalius Research Center, Laboratory for Translational Genetics, Department of Obstetrics and Gynecology, Department of Health Sciences Research, Department of Biostatistics, Department of Obstetrics and Gynecology, Centre for Cancerbiomarkers, Department of Obstetrics and Gynecology, Hunter Medical Research Institute, Centre for Information Based Medicine, School of Biomedical Sciences and Pharmacy, School of Medicine and Public Health, Grupo de investigación Citogenética, Genome Center and Department of Biochemistry and Molecular Medicine, Department of Molecular Medicine and Surgery, Department of Women's and Children's Health, Hunter Area Pathology Service, Centre for Clinical Epidemiology and Biostatistics, Institute of Health and Biomedical Innovation, Centre for Epidemiology and Biostatistics, Peter MacCallum Cancer Center, Division of Genetics and Epidemiology, Division of Breast Cancer Research, Department of Gynecology and Obstetrics, Division of Cancer Epidemiology, Division of Clinical Epidemiology and Aging Research, Division of Preventive Oncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Department of Obstetrics and Gynecology, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Department of Laboratory Medicine and Pathology, Cancer Epidemiology Centre, Department of Epidemiology and Preventive Medicine, Department of Genetics, The K.G. Jebsen Center for Breast Cancer Research, Department of Clinical Molecular Oncology, Department of Oncology, Faculty of Health and Medical Sciences, Department of Clinical Biochemistry, Department of Public Health and Primary Care, MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival (CNC), Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, Cambridge CB1 8RN, UK
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Department of Public Health and Primary Care, Department of Genetics and Computational Biology, Wellcome Trust Centre for Human Genetics, Academic Department of Biochemistry, Department of Clinical Genetics, Department of Oncology, Department of Medical Epidemiology and Biostatistics, Department of Medicine, Department of Gynecology and Obstetrics, Institute of Human Genetics, Gynaecology Research Unit, Clinics of Gynaecology and Obstetrics, Department of Gynaecology, Vesalius Research Center, Laboratory for Translational Genetics, Department of Obstetrics and Gynecology, Department of Health Sciences Research, Department of Biostatistics, Department of Obstetrics and Gynecology, Centre for Cancerbiomarkers, Department of Obstetrics and Gynecology, Hunter Medical Research Institute, Centre for Information Based Medicine, School of Biomedical Sciences and Pharmacy, School of Medicine and Public Health, Grupo de investigación Citogenética, Genome Center and Department of Biochemistry and Molecular Medicine, Department of Molecular Medicine and Surgery, Department of Women's and Children's Health, Hunter Area Pathology Service, Centre for Clinical Epidemiology and Biostatistics, Institute of Health and Biomedical Innovation, Centre for Epidemiology and Biostatistics, Peter MacCallum Cancer Center, Division of Genetics and Epidemiology, Division of Breast Cancer Research, Department of Gynecology and Obstetrics, Division of Cancer Epidemiology, Division of Clinical Epidemiology and Aging Research, Division of Preventive Oncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Department of Obstetrics and Gynecology, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Department of Laboratory Medicine and Pathology, Cancer Epidemiology Centre, Department of Epidemiology and Preventive Medicine, Department of Genetics, The K.G. Jebsen Center for Breast Cancer Research, Department of Clinical Molecular Oncology, Department of Oncology, Faculty of Health and Medical Sciences, Department of Clinical Biochemistry, Department of Public Health and Primary Care, MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival (CNC), Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, Cambridge CB1 8RN, UK
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Department of Public Health and Primary Care, Department of Genetics and Computational Biology, Wellcome Trust Centre for Human Genetics, Academic Department of Biochemistry, Department of Clinical Genetics, Department of Oncology, Department of Medical Epidemiology and Biostatistics, Department of Medicine, Department of Gynecology and Obstetrics, Institute of Human Genetics, Gynaecology Research Unit, Clinics of Gynaecology and Obstetrics, Department of Gynaecology, Vesalius Research Center, Laboratory for Translational Genetics, Department of Obstetrics and Gynecology, Department of Health Sciences Research, Department of Biostatistics, Department of Obstetrics and Gynecology, Centre for Cancerbiomarkers, Department of Obstetrics and Gynecology, Hunter Medical Research Institute, Centre for Information Based Medicine, School of Biomedical Sciences and Pharmacy, School of Medicine and Public Health, Grupo de investigación Citogenética, Genome Center and Department of Biochemistry and Molecular Medicine, Department of Molecular Medicine and Surgery, Department of Women's and Children's Health, Hunter Area Pathology Service, Centre for Clinical Epidemiology and Biostatistics, Institute of Health and Biomedical Innovation, Centre for Epidemiology and Biostatistics, Peter MacCallum Cancer Center, Division of Genetics and Epidemiology, Division of Breast Cancer Research, Department of Gynecology and Obstetrics, Division of Cancer Epidemiology, Division of Clinical Epidemiology and Aging Research, Division of Preventive Oncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Department of Obstetrics and Gynecology, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Department of Laboratory Medicine and Pathology, Cancer Epidemiology Centre, Department of Epidemiology and Preventive Medicine, Department of Genetics, The K.G. Jebsen Center for Breast Cancer Research, Department of Clinical Molecular Oncology, Department of Oncology, Faculty of Health and Medical Sciences, Department of Clinical Biochemistry, Department of Public Health and Primary Care, MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival (CNC), Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, Cambridge CB1 8RN, UK
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Department of Public Health and Primary Care, Department of Genetics and Computational Biology, Wellcome Trust Centre for Human Genetics, Academic Department of Biochemistry, Department of Clinical Genetics, Department of Oncology, Department of Medical Epidemiology and Biostatistics, Department of Medicine, Department of Gynecology and Obstetrics, Institute of Human Genetics, Gynaecology Research Unit, Clinics of Gynaecology and Obstetrics, Department of Gynaecology, Vesalius Research Center, Laboratory for Translational Genetics, Department of Obstetrics and Gynecology, Department of Health Sciences Research, Department of Biostatistics, Department of Obstetrics and Gynecology, Centre for Cancerbiomarkers, Department of Obstetrics and Gynecology, Hunter Medical Research Institute, Centre for Information Based Medicine, School of Biomedical Sciences and Pharmacy, School of Medicine and Public Health, Grupo de investigación Citogenética, Genome Center and Department of Biochemistry and Molecular Medicine, Department of Molecular Medicine and Surgery, Department of Women's and Children's Health, Hunter Area Pathology Service, Centre for Clinical Epidemiology and Biostatistics, Institute of Health and Biomedical Innovation, Centre for Epidemiology and Biostatistics, Peter MacCallum Cancer Center, Division of Genetics and Epidemiology, Division of Breast Cancer Research, Department of Gynecology and Obstetrics, Division of Cancer Epidemiology, Division of Clinical Epidemiology and Aging Research, Division of Preventive Oncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Department of Obstetrics and Gynecology, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Department of Laboratory Medicine and Pathology, Cancer Epidemiology Centre, Department of Epidemiology and Preventive Medicine, Department of Genetics, The K.G. Jebsen Center for Breast Cancer Research, Department of Clinical Molecular Oncology, Department of Oncology, Faculty of Health and Medical Sciences, Department of Clinical Biochemistry, Department of Public Health and Primary Care, MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival (CNC), Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, Cambridge CB1 8RN, UK
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Department of Public Health and Primary Care, Department of Genetics and Computational Biology, Wellcome Trust Centre for Human Genetics, Academic Department of Biochemistry, Department of Clinical Genetics, Department of Oncology, Department of Medical Epidemiology and Biostatistics, Department of Medicine, Department of Gynecology and Obstetrics, Institute of Human Genetics, Gynaecology Research Unit, Clinics of Gynaecology and Obstetrics, Department of Gynaecology, Vesalius Research Center, Laboratory for Translational Genetics, Department of Obstetrics and Gynecology, Department of Health Sciences Research, Department of Biostatistics, Department of Obstetrics and Gynecology, Centre for Cancerbiomarkers, Department of Obstetrics and Gynecology, Hunter Medical Research Institute, Centre for Information Based Medicine, School of Biomedical Sciences and Pharmacy, School of Medicine and Public Health, Grupo de investigación Citogenética, Genome Center and Department of Biochemistry and Molecular Medicine, Department of Molecular Medicine and Surgery, Department of Women's and Children's Health, Hunter Area Pathology Service, Centre for Clinical Epidemiology and Biostatistics, Institute of Health and Biomedical Innovation, Centre for Epidemiology and Biostatistics, Peter MacCallum Cancer Center, Division of Genetics and Epidemiology, Division of Breast Cancer Research, Department of Gynecology and Obstetrics, Division of Cancer Epidemiology, Division of Clinical Epidemiology and Aging Research, Division of Preventive Oncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Department of Obstetrics and Gynecology, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Department of Laboratory Medicine and Pathology, Cancer Epidemiology Centre, Department of Epidemiology and Preventive Medicine, Department of Genetics, The K.G. Jebsen Center for Breast Cancer Research, Department of Clinical Molecular Oncology, Department of Oncology, Faculty of Health and Medical Sciences, Department of Clinical Biochemistry, Department of Public Health and Primary Care, MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival (CNC), Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, Cambridge CB1 8RN, UK
Department of Public Health and Primary Care, Department of Genetics and Computational Biology, Wellcome Trust Centre for Human Genetics, Academic Department of Biochemistry, Department of Clinical Genetics, Department of Oncology, Department of Medical Epidemiology and Biostatistics, Department of Medicine, Department of Gynecology and Obstetrics, Institute of Human Genetics, Gynaecology Research Unit, Clinics of Gynaecology and Obstetrics, Department of Gynaecology, Vesalius Research Center, Laboratory for Translational Genetics, Department of Obstetrics and Gynecology, Department of Health Sciences Research, Department of Biostatistics, Department of Obstetrics and Gynecology, Centre for Cancerbiomarkers, Department of Obstetrics and Gynecology, Hunter Medical Research Institute, Centre for Information Based Medicine, School of Biomedical Sciences and Pharmacy, School of Medicine and Public Health, Grupo de investigación Citogenética, Genome Center and Department of Biochemistry and Molecular Medicine, Department of Molecular Medicine and Surgery, Department of Women's and Children's Health, Hunter Area Pathology Service, Centre for Clinical Epidemiology and Biostatistics, Institute of Health and Biomedical Innovation, Centre for Epidemiology and Biostatistics, Peter MacCallum Cancer Center, Division of Genetics and Epidemiology, Division of Breast Cancer Research, Department of Gynecology and Obstetrics, Division of Cancer Epidemiology, Division of Clinical Epidemiology and Aging Research, Division of Preventive Oncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Department of Obstetrics and Gynecology, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Department of Laboratory Medicine and Pathology, Cancer Epidemiology Centre, Department of Epidemiology and Preventive Medicine, Department of Genetics, The K.G. Jebsen Center for Breast Cancer Research, Department of Clinical Molecular Oncology, Department of Oncology, Faculty of Health and Medical Sciences, Department of Clinical Biochemistry, Department of Public Health and Primary Care, MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival (CNC), Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, Cambridge CB1 8RN, UK
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Department of Public Health and Primary Care, Department of Genetics and Computational Biology, Wellcome Trust Centre for Human Genetics, Academic Department of Biochemistry, Department of Clinical Genetics, Department of Oncology, Department of Medical Epidemiology and Biostatistics, Department of Medicine, Department of Gynecology and Obstetrics, Institute of Human Genetics, Gynaecology Research Unit, Clinics of Gynaecology and Obstetrics, Department of Gynaecology, Vesalius Research Center, Laboratory for Translational Genetics, Department of Obstetrics and Gynecology, Department of Health Sciences Research, Department of Biostatistics, Department of Obstetrics and Gynecology, Centre for Cancerbiomarkers, Department of Obstetrics and Gynecology, Hunter Medical Research Institute, Centre for Information Based Medicine, School of Biomedical Sciences and Pharmacy, School of Medicine and Public Health, Grupo de investigación Citogenética, Genome Center and Department of Biochemistry and Molecular Medicine, Department of Molecular Medicine and Surgery, Department of Women's and Children's Health, Hunter Area Pathology Service, Centre for Clinical Epidemiology and Biostatistics, Institute of Health and Biomedical Innovation, Centre for Epidemiology and Biostatistics, Peter MacCallum Cancer Center, Division of Genetics and Epidemiology, Division of Breast Cancer Research, Department of Gynecology and Obstetrics, Division of Cancer Epidemiology, Division of Clinical Epidemiology and Aging Research, Division of Preventive Oncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Department of Obstetrics and Gynecology, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Department of Laboratory Medicine and Pathology, Cancer Epidemiology Centre, Department of Epidemiology and Preventive Medicine, Department of Genetics, The K.G. Jebsen Center for Breast Cancer Research, Department of Clinical Molecular Oncology, Department of Oncology, Faculty of Health and Medical Sciences, Department of Clinical Biochemistry, Department of Public Health and Primary Care, MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival (CNC), Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, Cambridge CB1 8RN, UK
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Department of Public Health and Primary Care, Department of Genetics and Computational Biology, Wellcome Trust Centre for Human Genetics, Academic Department of Biochemistry, Department of Clinical Genetics, Department of Oncology, Department of Medical Epidemiology and Biostatistics, Department of Medicine, Department of Gynecology and Obstetrics, Institute of Human Genetics, Gynaecology Research Unit, Clinics of Gynaecology and Obstetrics, Department of Gynaecology, Vesalius Research Center, Laboratory for Translational Genetics, Department of Obstetrics and Gynecology, Department of Health Sciences Research, Department of Biostatistics, Department of Obstetrics and Gynecology, Centre for Cancerbiomarkers, Department of Obstetrics and Gynecology, Hunter Medical Research Institute, Centre for Information Based Medicine, School of Biomedical Sciences and Pharmacy, School of Medicine and Public Health, Grupo de investigación Citogenética, Genome Center and Department of Biochemistry and Molecular Medicine, Department of Molecular Medicine and Surgery, Department of Women's and Children's Health, Hunter Area Pathology Service, Centre for Clinical Epidemiology and Biostatistics, Institute of Health and Biomedical Innovation, Centre for Epidemiology and Biostatistics, Peter MacCallum Cancer Center, Division of Genetics and Epidemiology, Division of Breast Cancer Research, Department of Gynecology and Obstetrics, Division of Cancer Epidemiology, Division of Clinical Epidemiology and Aging Research, Division of Preventive Oncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Department of Obstetrics and Gynecology, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Department of Laboratory Medicine and Pathology, Cancer Epidemiology Centre, Department of Epidemiology and Preventive Medicine, Department of Genetics, The K.G. Jebsen Center for Breast Cancer Research, Department of Clinical Molecular Oncology, Department of Oncology, Faculty of Health and Medical Sciences, Department of Clinical Biochemistry, Department of Public Health and Primary Care, MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival (CNC), Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, Cambridge CB1 8RN, UK
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Department of Public Health and Primary Care, Department of Genetics and Computational Biology, Wellcome Trust Centre for Human Genetics, Academic Department of Biochemistry, Department of Clinical Genetics, Department of Oncology, Department of Medical Epidemiology and Biostatistics, Department of Medicine, Department of Gynecology and Obstetrics, Institute of Human Genetics, Gynaecology Research Unit, Clinics of Gynaecology and Obstetrics, Department of Gynaecology, Vesalius Research Center, Laboratory for Translational Genetics, Department of Obstetrics and Gynecology, Department of Health Sciences Research, Department of Biostatistics, Department of Obstetrics and Gynecology, Centre for Cancerbiomarkers, Department of Obstetrics and Gynecology, Hunter Medical Research Institute, Centre for Information Based Medicine, School of Biomedical Sciences and Pharmacy, School of Medicine and Public Health, Grupo de investigación Citogenética, Genome Center and Department of Biochemistry and Molecular Medicine, Department of Molecular Medicine and Surgery, Department of Women's and Children's Health, Hunter Area Pathology Service, Centre for Clinical Epidemiology and Biostatistics, Institute of Health and Biomedical Innovation, Centre for Epidemiology and Biostatistics, Peter MacCallum Cancer Center, Division of Genetics and Epidemiology, Division of Breast Cancer Research, Department of Gynecology and Obstetrics, Division of Cancer Epidemiology, Division of Clinical Epidemiology and Aging Research, Division of Preventive Oncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Department of Obstetrics and Gynecology, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Department of Laboratory Medicine and Pathology, Cancer Epidemiology Centre, Department of Epidemiology and Preventive Medicine, Department of Genetics, The K.G. Jebsen Center for Breast Cancer Research, Department of Clinical Molecular Oncology, Department of Oncology, Faculty of Health and Medical Sciences, Department of Clinical Biochemistry, Department of Public Health and Primary Care, MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival (CNC), Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, Cambridge CB1 8RN, UK
Department of Public Health and Primary Care, Department of Genetics and Computational Biology, Wellcome Trust Centre for Human Genetics, Academic Department of Biochemistry, Department of Clinical Genetics, Department of Oncology, Department of Medical Epidemiology and Biostatistics, Department of Medicine, Department of Gynecology and Obstetrics, Institute of Human Genetics, Gynaecology Research Unit, Clinics of Gynaecology and Obstetrics, Department of Gynaecology, Vesalius Research Center, Laboratory for Translational Genetics, Department of Obstetrics and Gynecology, Department of Health Sciences Research, Department of Biostatistics, Department of Obstetrics and Gynecology, Centre for Cancerbiomarkers, Department of Obstetrics and Gynecology, Hunter Medical Research Institute, Centre for Information Based Medicine, School of Biomedical Sciences and Pharmacy, School of Medicine and Public Health, Grupo de investigación Citogenética, Genome Center and Department of Biochemistry and Molecular Medicine, Department of Molecular Medicine and Surgery, Department of Women's and Children's Health, Hunter Area Pathology Service, Centre for Clinical Epidemiology and Biostatistics, Institute of Health and Biomedical Innovation, Centre for Epidemiology and Biostatistics, Peter MacCallum Cancer Center, Division of Genetics and Epidemiology, Division of Breast Cancer Research, Department of Gynecology and Obstetrics, Division of Cancer Epidemiology, Division of Clinical Epidemiology and Aging Research, Division of Preventive Oncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Department of Obstetrics and Gynecology, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Department of Laboratory Medicine and Pathology, Cancer Epidemiology Centre, Department of Epidemiology and Preventive Medicine, Department of Genetics, The K.G. Jebsen Center for Breast Cancer Research, Department of Clinical Molecular Oncology, Department of Oncology, Faculty of Health and Medical Sciences, Department of Clinical Biochemistry, Department of Public Health and Primary Care, MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival (CNC), Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, Cambridge CB1 8RN, UK
Department of Public Health and Primary Care, Department of Genetics and Computational Biology, Wellcome Trust Centre for Human Genetics, Academic Department of Biochemistry, Department of Clinical Genetics, Department of Oncology, Department of Medical Epidemiology and Biostatistics, Department of Medicine, Department of Gynecology and Obstetrics, Institute of Human Genetics, Gynaecology Research Unit, Clinics of Gynaecology and Obstetrics, Department of Gynaecology, Vesalius Research Center, Laboratory for Translational Genetics, Department of Obstetrics and Gynecology, Department of Health Sciences Research, Department of Biostatistics, Department of Obstetrics and Gynecology, Centre for Cancerbiomarkers, Department of Obstetrics and Gynecology, Hunter Medical Research Institute, Centre for Information Based Medicine, School of Biomedical Sciences and Pharmacy, School of Medicine and Public Health, Grupo de investigación Citogenética, Genome Center and Department of Biochemistry and Molecular Medicine, Department of Molecular Medicine and Surgery, Department of Women's and Children's Health, Hunter Area Pathology Service, Centre for Clinical Epidemiology and Biostatistics, Institute of Health and Biomedical Innovation, Centre for Epidemiology and Biostatistics, Peter MacCallum Cancer Center, Division of Genetics and Epidemiology, Division of Breast Cancer Research, Department of Gynecology and Obstetrics, Division of Cancer Epidemiology, Division of Clinical Epidemiology and Aging Research, Division of Preventive Oncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Department of Obstetrics and Gynecology, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Department of Laboratory Medicine and Pathology, Cancer Epidemiology Centre, Department of Epidemiology and Preventive Medicine, Department of Genetics, The K.G. Jebsen Center for Breast Cancer Research, Department of Clinical Molecular Oncology, Department of Oncology, Faculty of Health and Medical Sciences, Department of Clinical Biochemistry, Department of Public Health and Primary Care, MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival (CNC), Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, Cambridge CB1 8RN, UK
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Department of Public Health and Primary Care, Department of Genetics and Computational Biology, Wellcome Trust Centre for Human Genetics, Academic Department of Biochemistry, Department of Clinical Genetics, Department of Oncology, Department of Medical Epidemiology and Biostatistics, Department of Medicine, Department of Gynecology and Obstetrics, Institute of Human Genetics, Gynaecology Research Unit, Clinics of Gynaecology and Obstetrics, Department of Gynaecology, Vesalius Research Center, Laboratory for Translational Genetics, Department of Obstetrics and Gynecology, Department of Health Sciences Research, Department of Biostatistics, Department of Obstetrics and Gynecology, Centre for Cancerbiomarkers, Department of Obstetrics and Gynecology, Hunter Medical Research Institute, Centre for Information Based Medicine, School of Biomedical Sciences and Pharmacy, School of Medicine and Public Health, Grupo de investigación Citogenética, Genome Center and Department of Biochemistry and Molecular Medicine, Department of Molecular Medicine and Surgery, Department of Women's and Children's Health, Hunter Area Pathology Service, Centre for Clinical Epidemiology and Biostatistics, Institute of Health and Biomedical Innovation, Centre for Epidemiology and Biostatistics, Peter MacCallum Cancer Center, Division of Genetics and Epidemiology, Division of Breast Cancer Research, Department of Gynecology and Obstetrics, Division of Cancer Epidemiology, Division of Clinical Epidemiology and Aging Research, Division of Preventive Oncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Department of Obstetrics and Gynecology, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Department of Laboratory Medicine and Pathology, Cancer Epidemiology Centre, Department of Epidemiology and Preventive Medicine, Department of Genetics, The K.G. Jebsen Center for Breast Cancer Research, Department of Clinical Molecular Oncology, Department of Oncology, Faculty of Health and Medical Sciences, Department of Clinical Biochemistry, Department of Public Health and Primary Care, MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival (CNC), Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, Cambridge CB1 8RN, UK
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Department of Public Health and Primary Care, Department of Genetics and Computational Biology, Wellcome Trust Centre for Human Genetics, Academic Department of Biochemistry, Department of Clinical Genetics, Department of Oncology, Department of Medical Epidemiology and Biostatistics, Department of Medicine, Department of Gynecology and Obstetrics, Institute of Human Genetics, Gynaecology Research Unit, Clinics of Gynaecology and Obstetrics, Department of Gynaecology, Vesalius Research Center, Laboratory for Translational Genetics, Department of Obstetrics and Gynecology, Department of Health Sciences Research, Department of Biostatistics, Department of Obstetrics and Gynecology, Centre for Cancerbiomarkers, Department of Obstetrics and Gynecology, Hunter Medical Research Institute, Centre for Information Based Medicine, School of Biomedical Sciences and Pharmacy, School of Medicine and Public Health, Grupo de investigación Citogenética, Genome Center and Department of Biochemistry and Molecular Medicine, Department of Molecular Medicine and Surgery, Department of Women's and Children's Health, Hunter Area Pathology Service, Centre for Clinical Epidemiology and Biostatistics, Institute of Health and Biomedical Innovation, Centre for Epidemiology and Biostatistics, Peter MacCallum Cancer Center, Division of Genetics and Epidemiology, Division of Breast Cancer Research, Department of Gynecology and Obstetrics, Division of Cancer Epidemiology, Division of Clinical Epidemiology and Aging Research, Division of Preventive Oncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Department of Obstetrics and Gynecology, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Department of Laboratory Medicine and Pathology, Cancer Epidemiology Centre, Department of Epidemiology and Preventive Medicine, Department of Genetics, The K.G. Jebsen Center for Breast Cancer Research, Department of Clinical Molecular Oncology, Department of Oncology, Faculty of Health and Medical Sciences, Department of Clinical Biochemistry, Department of Public Health and Primary Care, MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival (CNC), Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, Cambridge CB1 8RN, UK
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Department of Public Health and Primary Care, Department of Genetics and Computational Biology, Wellcome Trust Centre for Human Genetics, Academic Department of Biochemistry, Department of Clinical Genetics, Department of Oncology, Department of Medical Epidemiology and Biostatistics, Department of Medicine, Department of Gynecology and Obstetrics, Institute of Human Genetics, Gynaecology Research Unit, Clinics of Gynaecology and Obstetrics, Department of Gynaecology, Vesalius Research Center, Laboratory for Translational Genetics, Department of Obstetrics and Gynecology, Department of Health Sciences Research, Department of Biostatistics, Department of Obstetrics and Gynecology, Centre for Cancerbiomarkers, Department of Obstetrics and Gynecology, Hunter Medical Research Institute, Centre for Information Based Medicine, School of Biomedical Sciences and Pharmacy, School of Medicine and Public Health, Grupo de investigación Citogenética, Genome Center and Department of Biochemistry and Molecular Medicine, Department of Molecular Medicine and Surgery, Department of Women's and Children's Health, Hunter Area Pathology Service, Centre for Clinical Epidemiology and Biostatistics, Institute of Health and Biomedical Innovation, Centre for Epidemiology and Biostatistics, Peter MacCallum Cancer Center, Division of Genetics and Epidemiology, Division of Breast Cancer Research, Department of Gynecology and Obstetrics, Division of Cancer Epidemiology, Division of Clinical Epidemiology and Aging Research, Division of Preventive Oncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Department of Obstetrics and Gynecology, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Department of Laboratory Medicine and Pathology, Cancer Epidemiology Centre, Department of Epidemiology and Preventive Medicine, Department of Genetics, The K.G. Jebsen Center for Breast Cancer Research, Department of Clinical Molecular Oncology, Department of Oncology, Faculty of Health and Medical Sciences, Department of Clinical Biochemistry, Department of Public Health and Primary Care, MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival (CNC), Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, Cambridge CB1 8RN, UK
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Department of Public Health and Primary Care, Department of Genetics and Computational Biology, Wellcome Trust Centre for Human Genetics, Academic Department of Biochemistry, Department of Clinical Genetics, Department of Oncology, Department of Medical Epidemiology and Biostatistics, Department of Medicine, Department of Gynecology and Obstetrics, Institute of Human Genetics, Gynaecology Research Unit, Clinics of Gynaecology and Obstetrics, Department of Gynaecology, Vesalius Research Center, Laboratory for Translational Genetics, Department of Obstetrics and Gynecology, Department of Health Sciences Research, Department of Biostatistics, Department of Obstetrics and Gynecology, Centre for Cancerbiomarkers, Department of Obstetrics and Gynecology, Hunter Medical Research Institute, Centre for Information Based Medicine, School of Biomedical Sciences and Pharmacy, School of Medicine and Public Health, Grupo de investigación Citogenética, Genome Center and Department of Biochemistry and Molecular Medicine, Department of Molecular Medicine and Surgery, Department of Women's and Children's Health, Hunter Area Pathology Service, Centre for Clinical Epidemiology and Biostatistics, Institute of Health and Biomedical Innovation, Centre for Epidemiology and Biostatistics, Peter MacCallum Cancer Center, Division of Genetics and Epidemiology, Division of Breast Cancer Research, Department of Gynecology and Obstetrics, Division of Cancer Epidemiology, Division of Clinical Epidemiology and Aging Research, Division of Preventive Oncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Department of Obstetrics and Gynecology, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Department of Laboratory Medicine and Pathology, Cancer Epidemiology Centre, Department of Epidemiology and Preventive Medicine, Department of Genetics, The K.G. Jebsen Center for Breast Cancer Research, Department of Clinical Molecular Oncology, Department of Oncology, Faculty of Health and Medical Sciences, Department of Clinical Biochemistry, Department of Public Health and Primary Care, MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival (CNC), Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, Cambridge CB1 8RN, UK
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Department of Public Health and Primary Care, Department of Genetics and Computational Biology, Wellcome Trust Centre for Human Genetics, Academic Department of Biochemistry, Department of Clinical Genetics, Department of Oncology, Department of Medical Epidemiology and Biostatistics, Department of Medicine, Department of Gynecology and Obstetrics, Institute of Human Genetics, Gynaecology Research Unit, Clinics of Gynaecology and Obstetrics, Department of Gynaecology, Vesalius Research Center, Laboratory for Translational Genetics, Department of Obstetrics and Gynecology, Department of Health Sciences Research, Department of Biostatistics, Department of Obstetrics and Gynecology, Centre for Cancerbiomarkers, Department of Obstetrics and Gynecology, Hunter Medical Research Institute, Centre for Information Based Medicine, School of Biomedical Sciences and Pharmacy, School of Medicine and Public Health, Grupo de investigación Citogenética, Genome Center and Department of Biochemistry and Molecular Medicine, Department of Molecular Medicine and Surgery, Department of Women's and Children's Health, Hunter Area Pathology Service, Centre for Clinical Epidemiology and Biostatistics, Institute of Health and Biomedical Innovation, Centre for Epidemiology and Biostatistics, Peter MacCallum Cancer Center, Division of Genetics and Epidemiology, Division of Breast Cancer Research, Department of Gynecology and Obstetrics, Division of Cancer Epidemiology, Division of Clinical Epidemiology and Aging Research, Division of Preventive Oncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Department of Obstetrics and Gynecology, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Department of Laboratory Medicine and Pathology, Cancer Epidemiology Centre, Department of Epidemiology and Preventive Medicine, Department of Genetics, The K.G. Jebsen Center for Breast Cancer Research, Department of Clinical Molecular Oncology, Department of Oncology, Faculty of Health and Medical Sciences, Department of Clinical Biochemistry, Department of Public Health and Primary Care, MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival (CNC), Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, Cambridge CB1 8RN, UK
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Department of Public Health and Primary Care, Department of Genetics and Computational Biology, Wellcome Trust Centre for Human Genetics, Academic Department of Biochemistry, Department of Clinical Genetics, Department of Oncology, Department of Medical Epidemiology and Biostatistics, Department of Medicine, Department of Gynecology and Obstetrics, Institute of Human Genetics, Gynaecology Research Unit, Clinics of Gynaecology and Obstetrics, Department of Gynaecology, Vesalius Research Center, Laboratory for Translational Genetics, Department of Obstetrics and Gynecology, Department of Health Sciences Research, Department of Biostatistics, Department of Obstetrics and Gynecology, Centre for Cancerbiomarkers, Department of Obstetrics and Gynecology, Hunter Medical Research Institute, Centre for Information Based Medicine, School of Biomedical Sciences and Pharmacy, School of Medicine and Public Health, Grupo de investigación Citogenética, Genome Center and Department of Biochemistry and Molecular Medicine, Department of Molecular Medicine and Surgery, Department of Women's and Children's Health, Hunter Area Pathology Service, Centre for Clinical Epidemiology and Biostatistics, Institute of Health and Biomedical Innovation, Centre for Epidemiology and Biostatistics, Peter MacCallum Cancer Center, Division of Genetics and Epidemiology, Division of Breast Cancer Research, Department of Gynecology and Obstetrics, Division of Cancer Epidemiology, Division of Clinical Epidemiology and Aging Research, Division of Preventive Oncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Department of Obstetrics and Gynecology, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Department of Laboratory Medicine and Pathology, Cancer Epidemiology Centre, Department of Epidemiology and Preventive Medicine, Department of Genetics, The K.G. Jebsen Center for Breast Cancer Research, Department of Clinical Molecular Oncology, Department of Oncology, Faculty of Health and Medical Sciences, Department of Clinical Biochemistry, Department of Public Health and Primary Care, MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival (CNC), Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, Cambridge CB1 8RN, UK
Department of Public Health and Primary Care, Department of Genetics and Computational Biology, Wellcome Trust Centre for Human Genetics, Academic Department of Biochemistry, Department of Clinical Genetics, Department of Oncology, Department of Medical Epidemiology and Biostatistics, Department of Medicine, Department of Gynecology and Obstetrics, Institute of Human Genetics, Gynaecology Research Unit, Clinics of Gynaecology and Obstetrics, Department of Gynaecology, Vesalius Research Center, Laboratory for Translational Genetics, Department of Obstetrics and Gynecology, Department of Health Sciences Research, Department of Biostatistics, Department of Obstetrics and Gynecology, Centre for Cancerbiomarkers, Department of Obstetrics and Gynecology, Hunter Medical Research Institute, Centre for Information Based Medicine, School of Biomedical Sciences and Pharmacy, School of Medicine and Public Health, Grupo de investigación Citogenética, Genome Center and Department of Biochemistry and Molecular Medicine, Department of Molecular Medicine and Surgery, Department of Women's and Children's Health, Hunter Area Pathology Service, Centre for Clinical Epidemiology and Biostatistics, Institute of Health and Biomedical Innovation, Centre for Epidemiology and Biostatistics, Peter MacCallum Cancer Center, Division of Genetics and Epidemiology, Division of Breast Cancer Research, Department of Gynecology and Obstetrics, Division of Cancer Epidemiology, Division of Clinical Epidemiology and Aging Research, Division of Preventive Oncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Department of Obstetrics and Gynecology, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Department of Laboratory Medicine and Pathology, Cancer Epidemiology Centre, Department of Epidemiology and Preventive Medicine, Department of Genetics, The K.G. Jebsen Center for Breast Cancer Research, Department of Clinical Molecular Oncology, Department of Oncology, Faculty of Health and Medical Sciences, Department of Clinical Biochemistry, Department of Public Health and Primary Care, MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival (CNC), Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, Cambridge CB1 8RN, UK
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Department of Public Health and Primary Care, Department of Genetics and Computational Biology, Wellcome Trust Centre for Human Genetics, Academic Department of Biochemistry, Department of Clinical Genetics, Department of Oncology, Department of Medical Epidemiology and Biostatistics, Department of Medicine, Department of Gynecology and Obstetrics, Institute of Human Genetics, Gynaecology Research Unit, Clinics of Gynaecology and Obstetrics, Department of Gynaecology, Vesalius Research Center, Laboratory for Translational Genetics, Department of Obstetrics and Gynecology, Department of Health Sciences Research, Department of Biostatistics, Department of Obstetrics and Gynecology, Centre for Cancerbiomarkers, Department of Obstetrics and Gynecology, Hunter Medical Research Institute, Centre for Information Based Medicine, School of Biomedical Sciences and Pharmacy, School of Medicine and Public Health, Grupo de investigación Citogenética, Genome Center and Department of Biochemistry and Molecular Medicine, Department of Molecular Medicine and Surgery, Department of Women's and Children's Health, Hunter Area Pathology Service, Centre for Clinical Epidemiology and Biostatistics, Institute of Health and Biomedical Innovation, Centre for Epidemiology and Biostatistics, Peter MacCallum Cancer Center, Division of Genetics and Epidemiology, Division of Breast Cancer Research, Department of Gynecology and Obstetrics, Division of Cancer Epidemiology, Division of Clinical Epidemiology and Aging Research, Division of Preventive Oncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Department of Obstetrics and Gynecology, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Department of Laboratory Medicine and Pathology, Cancer Epidemiology Centre, Department of Epidemiology and Preventive Medicine, Department of Genetics, The K.G. Jebsen Center for Breast Cancer Research, Department of Clinical Molecular Oncology, Department of Oncology, Faculty of Health and Medical Sciences, Department of Clinical Biochemistry, Department of Public Health and Primary Care, MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival (CNC), Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, Cambridge CB1 8RN, UK
Department of Public Health and Primary Care, Department of Genetics and Computational Biology, Wellcome Trust Centre for Human Genetics, Academic Department of Biochemistry, Department of Clinical Genetics, Department of Oncology, Department of Medical Epidemiology and Biostatistics, Department of Medicine, Department of Gynecology and Obstetrics, Institute of Human Genetics, Gynaecology Research Unit, Clinics of Gynaecology and Obstetrics, Department of Gynaecology, Vesalius Research Center, Laboratory for Translational Genetics, Department of Obstetrics and Gynecology, Department of Health Sciences Research, Department of Biostatistics, Department of Obstetrics and Gynecology, Centre for Cancerbiomarkers, Department of Obstetrics and Gynecology, Hunter Medical Research Institute, Centre for Information Based Medicine, School of Biomedical Sciences and Pharmacy, School of Medicine and Public Health, Grupo de investigación Citogenética, Genome Center and Department of Biochemistry and Molecular Medicine, Department of Molecular Medicine and Surgery, Department of Women's and Children's Health, Hunter Area Pathology Service, Centre for Clinical Epidemiology and Biostatistics, Institute of Health and Biomedical Innovation, Centre for Epidemiology and Biostatistics, Peter MacCallum Cancer Center, Division of Genetics and Epidemiology, Division of Breast Cancer Research, Department of Gynecology and Obstetrics, Division of Cancer Epidemiology, Division of Clinical Epidemiology and Aging Research, Division of Preventive Oncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Department of Obstetrics and Gynecology, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Department of Laboratory Medicine and Pathology, Cancer Epidemiology Centre, Department of Epidemiology and Preventive Medicine, Department of Genetics, The K.G. Jebsen Center for Breast Cancer Research, Department of Clinical Molecular Oncology, Department of Oncology, Faculty of Health and Medical Sciences, Department of Clinical Biochemistry, Department of Public Health and Primary Care, MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival (CNC), Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, Cambridge CB1 8RN, UK
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Department of Public Health and Primary Care, Department of Genetics and Computational Biology, Wellcome Trust Centre for Human Genetics, Academic Department of Biochemistry, Department of Clinical Genetics, Department of Oncology, Department of Medical Epidemiology and Biostatistics, Department of Medicine, Department of Gynecology and Obstetrics, Institute of Human Genetics, Gynaecology Research Unit, Clinics of Gynaecology and Obstetrics, Department of Gynaecology, Vesalius Research Center, Laboratory for Translational Genetics, Department of Obstetrics and Gynecology, Department of Health Sciences Research, Department of Biostatistics, Department of Obstetrics and Gynecology, Centre for Cancerbiomarkers, Department of Obstetrics and Gynecology, Hunter Medical Research Institute, Centre for Information Based Medicine, School of Biomedical Sciences and Pharmacy, School of Medicine and Public Health, Grupo de investigación Citogenética, Genome Center and Department of Biochemistry and Molecular Medicine, Department of Molecular Medicine and Surgery, Department of Women's and Children's Health, Hunter Area Pathology Service, Centre for Clinical Epidemiology and Biostatistics, Institute of Health and Biomedical Innovation, Centre for Epidemiology and Biostatistics, Peter MacCallum Cancer Center, Division of Genetics and Epidemiology, Division of Breast Cancer Research, Department of Gynecology and Obstetrics, Division of Cancer Epidemiology, Division of Clinical Epidemiology and Aging Research, Division of Preventive Oncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Department of Obstetrics and Gynecology, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Department of Laboratory Medicine and Pathology, Cancer Epidemiology Centre, Department of Epidemiology and Preventive Medicine, Department of Genetics, The K.G. Jebsen Center for Breast Cancer Research, Department of Clinical Molecular Oncology, Department of Oncology, Faculty of Health and Medical Sciences, Department of Clinical Biochemistry, Department of Public Health and Primary Care, MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival (CNC), Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, Cambridge CB1 8RN, UK
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Department of Public Health and Primary Care, Department of Genetics and Computational Biology, Wellcome Trust Centre for Human Genetics, Academic Department of Biochemistry, Department of Clinical Genetics, Department of Oncology, Department of Medical Epidemiology and Biostatistics, Department of Medicine, Department of Gynecology and Obstetrics, Institute of Human Genetics, Gynaecology Research Unit, Clinics of Gynaecology and Obstetrics, Department of Gynaecology, Vesalius Research Center, Laboratory for Translational Genetics, Department of Obstetrics and Gynecology, Department of Health Sciences Research, Department of Biostatistics, Department of Obstetrics and Gynecology, Centre for Cancerbiomarkers, Department of Obstetrics and Gynecology, Hunter Medical Research Institute, Centre for Information Based Medicine, School of Biomedical Sciences and Pharmacy, School of Medicine and Public Health, Grupo de investigación Citogenética, Genome Center and Department of Biochemistry and Molecular Medicine, Department of Molecular Medicine and Surgery, Department of Women's and Children's Health, Hunter Area Pathology Service, Centre for Clinical Epidemiology and Biostatistics, Institute of Health and Biomedical Innovation, Centre for Epidemiology and Biostatistics, Peter MacCallum Cancer Center, Division of Genetics and Epidemiology, Division of Breast Cancer Research, Department of Gynecology and Obstetrics, Division of Cancer Epidemiology, Division of Clinical Epidemiology and Aging Research, Division of Preventive Oncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Department of Obstetrics and Gynecology, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Department of Laboratory Medicine and Pathology, Cancer Epidemiology Centre, Department of Epidemiology and Preventive Medicine, Department of Genetics, The K.G. Jebsen Center for Breast Cancer Research, Department of Clinical Molecular Oncology, Department of Oncology, Faculty of Health and Medical Sciences, Department of Clinical Biochemistry, Department of Public Health and Primary Care, MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival (CNC), Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, Cambridge CB1 8RN, UK
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Department of Public Health and Primary Care, Department of Genetics and Computational Biology, Wellcome Trust Centre for Human Genetics, Academic Department of Biochemistry, Department of Clinical Genetics, Department of Oncology, Department of Medical Epidemiology and Biostatistics, Department of Medicine, Department of Gynecology and Obstetrics, Institute of Human Genetics, Gynaecology Research Unit, Clinics of Gynaecology and Obstetrics, Department of Gynaecology, Vesalius Research Center, Laboratory for Translational Genetics, Department of Obstetrics and Gynecology, Department of Health Sciences Research, Department of Biostatistics, Department of Obstetrics and Gynecology, Centre for Cancerbiomarkers, Department of Obstetrics and Gynecology, Hunter Medical Research Institute, Centre for Information Based Medicine, School of Biomedical Sciences and Pharmacy, School of Medicine and Public Health, Grupo de investigación Citogenética, Genome Center and Department of Biochemistry and Molecular Medicine, Department of Molecular Medicine and Surgery, Department of Women's and Children's Health, Hunter Area Pathology Service, Centre for Clinical Epidemiology and Biostatistics, Institute of Health and Biomedical Innovation, Centre for Epidemiology and Biostatistics, Peter MacCallum Cancer Center, Division of Genetics and Epidemiology, Division of Breast Cancer Research, Department of Gynecology and Obstetrics, Division of Cancer Epidemiology, Division of Clinical Epidemiology and Aging Research, Division of Preventive Oncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Department of Obstetrics and Gynecology, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Department of Laboratory Medicine and Pathology, Cancer Epidemiology Centre, Department of Epidemiology and Preventive Medicine, Department of Genetics, The K.G. Jebsen Center for Breast Cancer Research, Department of Clinical Molecular Oncology, Department of Oncology, Faculty of Health and Medical Sciences, Department of Clinical Biochemistry, Department of Public Health and Primary Care, MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival (CNC), Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, Cambridge CB1 8RN, UK
Department of Public Health and Primary Care, Department of Genetics and Computational Biology, Wellcome Trust Centre for Human Genetics, Academic Department of Biochemistry, Department of Clinical Genetics, Department of Oncology, Department of Medical Epidemiology and Biostatistics, Department of Medicine, Department of Gynecology and Obstetrics, Institute of Human Genetics, Gynaecology Research Unit, Clinics of Gynaecology and Obstetrics, Department of Gynaecology, Vesalius Research Center, Laboratory for Translational Genetics, Department of Obstetrics and Gynecology, Department of Health Sciences Research, Department of Biostatistics, Department of Obstetrics and Gynecology, Centre for Cancerbiomarkers, Department of Obstetrics and Gynecology, Hunter Medical Research Institute, Centre for Information Based Medicine, School of Biomedical Sciences and Pharmacy, School of Medicine and Public Health, Grupo de investigación Citogenética, Genome Center and Department of Biochemistry and Molecular Medicine, Department of Molecular Medicine and Surgery, Department of Women's and Children's Health, Hunter Area Pathology Service, Centre for Clinical Epidemiology and Biostatistics, Institute of Health and Biomedical Innovation, Centre for Epidemiology and Biostatistics, Peter MacCallum Cancer Center, Division of Genetics and Epidemiology, Division of Breast Cancer Research, Department of Gynecology and Obstetrics, Division of Cancer Epidemiology, Division of Clinical Epidemiology and Aging Research, Division of Preventive Oncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Department of Obstetrics and Gynecology, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Department of Laboratory Medicine and Pathology, Cancer Epidemiology Centre, Department of Epidemiology and Preventive Medicine, Department of Genetics, The K.G. Jebsen Center for Breast Cancer Research, Department of Clinical Molecular Oncology, Department of Oncology, Faculty of Health and Medical Sciences, Department of Clinical Biochemistry, Department of Public Health and Primary Care, MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival (CNC), Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, Cambridge CB1 8RN, UK
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Department of Public Health and Primary Care, Department of Genetics and Computational Biology, Wellcome Trust Centre for Human Genetics, Academic Department of Biochemistry, Department of Clinical Genetics, Department of Oncology, Department of Medical Epidemiology and Biostatistics, Department of Medicine, Department of Gynecology and Obstetrics, Institute of Human Genetics, Gynaecology Research Unit, Clinics of Gynaecology and Obstetrics, Department of Gynaecology, Vesalius Research Center, Laboratory for Translational Genetics, Department of Obstetrics and Gynecology, Department of Health Sciences Research, Department of Biostatistics, Department of Obstetrics and Gynecology, Centre for Cancerbiomarkers, Department of Obstetrics and Gynecology, Hunter Medical Research Institute, Centre for Information Based Medicine, School of Biomedical Sciences and Pharmacy, School of Medicine and Public Health, Grupo de investigación Citogenética, Genome Center and Department of Biochemistry and Molecular Medicine, Department of Molecular Medicine and Surgery, Department of Women's and Children's Health, Hunter Area Pathology Service, Centre for Clinical Epidemiology and Biostatistics, Institute of Health and Biomedical Innovation, Centre for Epidemiology and Biostatistics, Peter MacCallum Cancer Center, Division of Genetics and Epidemiology, Division of Breast Cancer Research, Department of Gynecology and Obstetrics, Division of Cancer Epidemiology, Division of Clinical Epidemiology and Aging Research, Division of Preventive Oncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Department of Obstetrics and Gynecology, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Department of Laboratory Medicine and Pathology, Cancer Epidemiology Centre, Department of Epidemiology and Preventive Medicine, Department of Genetics, The K.G. Jebsen Center for Breast Cancer Research, Department of Clinical Molecular Oncology, Department of Oncology, Faculty of Health and Medical Sciences, Department of Clinical Biochemistry, Department of Public Health and Primary Care, MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival (CNC), Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, Cambridge CB1 8RN, UK
Department of Public Health and Primary Care, Department of Genetics and Computational Biology, Wellcome Trust Centre for Human Genetics, Academic Department of Biochemistry, Department of Clinical Genetics, Department of Oncology, Department of Medical Epidemiology and Biostatistics, Department of Medicine, Department of Gynecology and Obstetrics, Institute of Human Genetics, Gynaecology Research Unit, Clinics of Gynaecology and Obstetrics, Department of Gynaecology, Vesalius Research Center, Laboratory for Translational Genetics, Department of Obstetrics and Gynecology, Department of Health Sciences Research, Department of Biostatistics, Department of Obstetrics and Gynecology, Centre for Cancerbiomarkers, Department of Obstetrics and Gynecology, Hunter Medical Research Institute, Centre for Information Based Medicine, School of Biomedical Sciences and Pharmacy, School of Medicine and Public Health, Grupo de investigación Citogenética, Genome Center and Department of Biochemistry and Molecular Medicine, Department of Molecular Medicine and Surgery, Department of Women's and Children's Health, Hunter Area Pathology Service, Centre for Clinical Epidemiology and Biostatistics, Institute of Health and Biomedical Innovation, Centre for Epidemiology and Biostatistics, Peter MacCallum Cancer Center, Division of Genetics and Epidemiology, Division of Breast Cancer Research, Department of Gynecology and Obstetrics, Division of Cancer Epidemiology, Division of Clinical Epidemiology and Aging Research, Division of Preventive Oncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Department of Obstetrics and Gynecology, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Department of Laboratory Medicine and Pathology, Cancer Epidemiology Centre, Department of Epidemiology and Preventive Medicine, Department of Genetics, The K.G. Jebsen Center for Breast Cancer Research, Department of Clinical Molecular Oncology, Department of Oncology, Faculty of Health and Medical Sciences, Department of Clinical Biochemistry, Department of Public Health and Primary Care, MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival (CNC), Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, Cambridge CB1 8RN, UK
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Department of Public Health and Primary Care, Department of Genetics and Computational Biology, Wellcome Trust Centre for Human Genetics, Academic Department of Biochemistry, Department of Clinical Genetics, Department of Oncology, Department of Medical Epidemiology and Biostatistics, Department of Medicine, Department of Gynecology and Obstetrics, Institute of Human Genetics, Gynaecology Research Unit, Clinics of Gynaecology and Obstetrics, Department of Gynaecology, Vesalius Research Center, Laboratory for Translational Genetics, Department of Obstetrics and Gynecology, Department of Health Sciences Research, Department of Biostatistics, Department of Obstetrics and Gynecology, Centre for Cancerbiomarkers, Department of Obstetrics and Gynecology, Hunter Medical Research Institute, Centre for Information Based Medicine, School of Biomedical Sciences and Pharmacy, School of Medicine and Public Health, Grupo de investigación Citogenética, Genome Center and Department of Biochemistry and Molecular Medicine, Department of Molecular Medicine and Surgery, Department of Women's and Children's Health, Hunter Area Pathology Service, Centre for Clinical Epidemiology and Biostatistics, Institute of Health and Biomedical Innovation, Centre for Epidemiology and Biostatistics, Peter MacCallum Cancer Center, Division of Genetics and Epidemiology, Division of Breast Cancer Research, Department of Gynecology and Obstetrics, Division of Cancer Epidemiology, Division of Clinical Epidemiology and Aging Research, Division of Preventive Oncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Department of Obstetrics and Gynecology, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Department of Laboratory Medicine and Pathology, Cancer Epidemiology Centre, Department of Epidemiology and Preventive Medicine, Department of Genetics, The K.G. Jebsen Center for Breast Cancer Research, Department of Clinical Molecular Oncology, Department of Oncology, Faculty of Health and Medical Sciences, Department of Clinical Biochemistry, Department of Public Health and Primary Care, MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival (CNC), Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, Cambridge CB1 8RN, UK
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Department of Public Health and Primary Care, Department of Genetics and Computational Biology, Wellcome Trust Centre for Human Genetics, Academic Department of Biochemistry, Department of Clinical Genetics, Department of Oncology, Department of Medical Epidemiology and Biostatistics, Department of Medicine, Department of Gynecology and Obstetrics, Institute of Human Genetics, Gynaecology Research Unit, Clinics of Gynaecology and Obstetrics, Department of Gynaecology, Vesalius Research Center, Laboratory for Translational Genetics, Department of Obstetrics and Gynecology, Department of Health Sciences Research, Department of Biostatistics, Department of Obstetrics and Gynecology, Centre for Cancerbiomarkers, Department of Obstetrics and Gynecology, Hunter Medical Research Institute, Centre for Information Based Medicine, School of Biomedical Sciences and Pharmacy, School of Medicine and Public Health, Grupo de investigación Citogenética, Genome Center and Department of Biochemistry and Molecular Medicine, Department of Molecular Medicine and Surgery, Department of Women's and Children's Health, Hunter Area Pathology Service, Centre for Clinical Epidemiology and Biostatistics, Institute of Health and Biomedical Innovation, Centre for Epidemiology and Biostatistics, Peter MacCallum Cancer Center, Division of Genetics and Epidemiology, Division of Breast Cancer Research, Department of Gynecology and Obstetrics, Division of Cancer Epidemiology, Division of Clinical Epidemiology and Aging Research, Division of Preventive Oncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Department of Obstetrics and Gynecology, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Department of Laboratory Medicine and Pathology, Cancer Epidemiology Centre, Department of Epidemiology and Preventive Medicine, Department of Genetics, The K.G. Jebsen Center for Breast Cancer Research, Department of Clinical Molecular Oncology, Department of Oncology, Faculty of Health and Medical Sciences, Department of Clinical Biochemistry, Department of Public Health and Primary Care, MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival (CNC), Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, Cambridge CB1 8RN, UK
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Candidate gene studies have reported CYP19A1 variants to be associated with endometrial cancer and with estradiol (E2) concentrations. We analyzed 2937 single nucleotide polymorphisms (SNPs) in 6608 endometrial cancer cases and 37 925 controls and report the first genome wide-significant association between endometrial cancer and a CYP19A1 SNP (rs727479 in intron 2, P=4.8×10−11). SNP rs727479 was also among those most strongly associated with circulating E2 concentrations in 2767 post-menopausal controls (P=7.4×10−8). The observed endometrial cancer odds ratio per rs727479 A-allele (1.15, CI=1.11–1.21) is compatible with that predicted by the observed effect on E2 concentrations (1.09, CI=1.03–1.21), consistent with the hypothesis that endometrial cancer risk is driven by E2. From 28 candidate-causal SNPs, 12 co-located with three putative gene-regulatory elements and their risk alleles associated with higher CYP19A1 expression in bioinformatical analyses. For both phenotypes, the associations with rs727479 were stronger among women with a higher BMI (P interaction=0.034 and 0.066 respectively), suggesting a biologically plausible gene-environment interaction.