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Division of Cancer Epidemiology, Division of Molecular Genetic Epidemiology, Division of Clinical Epidemiology and Aging Research, Center for Primary Health Care Research, German Cancer Research Center, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany
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Division of Cancer Epidemiology, Division of Molecular Genetic Epidemiology, Division of Clinical Epidemiology and Aging Research, Center for Primary Health Care Research, German Cancer Research Center, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany
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The mechanisms underlying the association of menopausal hormone therapy (MHT) with reduced colorectal cancer (CRC) risk are unknown and the identification of genetic modifiers may yield further insight. We explored the effect modification of MHT-associated CRC risk in postmenopausal women by 47 polymorphisms with known or putative functional relevance in 16 candidate genes related to hormone metabolism (COMT, CYP1A1, CYP1A2, CYP1B1, CYP2C9, CYP2C19, CYP3A4, CYP17A1, GSTP, and HSD17B1), transport (ABCB1), and signaling (ESR1, ESR2, SHBG, PGR, and NR1I2). A total of 685 CRC patients and 684 healthy controls from a German population-based case–control study (DACHS) were genotyped. Multiplicative statistical interaction between polymorphisms and ever MHT use as well as duration of use was assessed using multivariate logistic regression. CRC risk associated with ever MHT use as well as with duration was significantly modified by rs1202168 in the transporter gene ABCB1 (P interaction=0.04). The MHT-associated risk reduction was not significant in homozygous non-carriers (odds ratio (OR) ever use=0.84, 95% confidence interval (CI) 0.53–1.34; OR per 5 year duration=0.94, 95% CI 0.83–1.08), while homozygous carriers of the minor T allele had a 57% lower risk with ever use of MHT (95% CI 0.21–0.88) and a 22% lower risk per 5 years of MHT use (95% CI 0.62–0.97). Significant effect modification was also observed for the ESR1_rs910416 polymorphism (P interaction=0.03 for ever use and 0.07 for duration of use), whereby the decreased risk was attenuated in homozygous carriers of the minor C allele (OR ever use=0.87, 95% CI 0.48–1.60, OR per 5 year duration=0.99, 95% CI 0.83–1.18). Results of this exploratory study provide first evidence that polymorphisms in genes related to estrogen transport and signaling may modify MHT-associated CRC risk but warrant replication in an independent population.
Institute of Pathology, Department of Pathology, Department of Pathology, Department of Urology, Institute of Pathology, Department of Pathology, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany
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Institute of Pathology, Department of Pathology, Department of Pathology, Department of Urology, Institute of Pathology, Department of Pathology, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany
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Prediction of malignant behaviour of pheochromocytomas/sympathetic paragangliomas (PCCs/PGLs) is very difficult if not impossible on a histopathological basis. In a familial setting, it is well known that succinate dehydrogenase subunit B (SDHB)-associated PCC/PGL very often metastasise. Recently, absence of SDHB expression as measured through immunohistochemistry was shown to be an excellent indicator of the presence of an SDH germline mutation in PCC/PGL. SDHB loss is believed to lead to tumour formation by activation of hypoxia signals. To clarify the potential use of SDHB immunohistochemistry as a marker of malignancy in PCC/PGL and its association with classic hypoxia signalling we examined SDHB, hypoxia inducible factor-1α (Hif-1α) and its targets CA-9 and GLUT-1 expression on protein level using immunohistochemistry on a tissue micro array on a series of familial and sporadic tumours of 115 patients. Survival data was available for 66 patients. SDHB protein expression was lost in the tumour tissue of 12 of 99 patients. Of those 12 patients, 5 had an SDHB germline mutation, in 4 patients no germline mutation was detected and mutational status remained unknown in parts in 3 patients. Loss of SDHB expression was not associated with increased classic hypoxia signalling as detected by Hif-1α, CA-9 or GLUT-1 staining. Loss of SDHB expression was associated with an adverse outcome. The lack of correlation of SDHB loss with classic hypoxia signals argues against the current hypoxia hypothesis in malignant PCC/PGL. We suggest SDHB protein loss as a marker of adverse outcome both in sporadic and in familial PCC/PGL.
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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.