CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers
Copyright policy )CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers
Abstract Background Epidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk. Methods We carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women. To test for the association with breast cancer risk, we carried out follow-up genotyping in 90,916 cases and 89,893 controls from the Breast Cancer Association Consortium. All women were of European ancestry. Results For pregnanediol-3-glucuronide, there were no genome-wide significant associations; for oestrone-3-glucuronide, we identified a single peak mapping to the CYP3A locus, annotated by rs45446698. The minor rs45446698-C allele was associated with lower oestrone-3-glucuronide (−49.2%, 95% CI −56.1% to −41.1%, P = 3.1 × 10–18); in follow-up analyses, rs45446698-C was also associated with lower progesterone (−26.7%, 95% CI −39.4% to −11.6%, P = 0.001) and reduced risk of oestrogen and progesterone receptor-positive breast cancer (OR = 0.86, 95% CI 0.82–0.91, P = 6.9 × 10–8). Conclusions The CYP3A7*1C allele is associated with reduced risk of hormone receptor-positive breast cancer possibly mediated via an effect on the metabolism of endogenous sex hormones in premenopausal women.
- Imperial College London United Kingdom
- Mayo Clinic United States
- Stanford University United States
- University of Toronto Canada
- Antoni van Leeuwenhoek Hospital Netherlands
Aging, 1117 Public Health and Health Services (for), receptor, Progesterone (mesh), Sustainable Development Goals, Medical Genetics and Genomics, Aging (rcdc), IMPUTATION, Estrone (mesh), /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being; name=SDG 3 - Good Health and Well-being, Aetiology, 32 Biomedical and Clinical Sciences (for-2020), Estrogen (mesh), Progesterone, Cancer, SDG 3, AOCS Group, 1112 Oncology and Carcinogenesis (for), Breast Cancer (rcdc), Premenopause (mesh), Oncology, Receptors, Estrogen, Public Health and Health Services, Alleles (mesh), Pregnanediol, Receptors, Progesterone, ABCTB Investigators, 610, /631/67/2324, progesterone, Article, SDG 3 - Good Health and Well-being, Clinical Research, 616, Genetics, 3211 Oncology and carcinogenesis (for-2020), Humans, Polymorphism, GENOME-WIDE ASSOCIATION, Alleles, Science & Technology, Genetics (rcdc), Cancer (hrcs-hc), /631/67/1347, Alleles; Breast Neoplasms; Case-Control Studies; Cytochrome P-450 CYP3A; Estrone; Female; Genome-Wide Association Study; Humans; Polymorphism, Single Nucleotide; Pregnanediol; Premenopause; Progesterone; Receptors, Estrogen; Receptors, Progesterone, Human Genome (rcdc), name=SDG 3 - Good Health and Well-being, 3211 Oncology and Carcinogenesis (for-2020), Premenopause, Oncology & Carcinogenesis (science-metrix), Case-Control Studies, CYP3A5, Women's Health (rcdc), Cytochrome P-450 CYP3A (mesh), Clinical Research (rcdc), Receptors, 2.1 Biological and endogenous factors, Cytochrome P-450 CYP3A, Cancer (rcdc), Humans (mesh), article, Single Nucleotide, estrone, Medicinsk genetik och genomik, /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being, kConFab Investigators, Genome-Wide Association Study (mesh), Female, Medical Genetics, Life Sciences & Biomedicine, Estrogen (rcdc), Single Nucleotide (mesh), Estrone, Oncology and Carcinogenesis, EMC OR-01, Breast Neoplasms, Pregnanediol (mesh), Polymorphism, Single Nucleotide, Case-Control Studies (mesh), NBCS Collaborators, 1117 Public Health and Health Services, Breast Neoplasms (mesh), 3211 Oncology and carcinogenesis, /631/67/68, Breast Cancer, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, breast, Medicinsk genetik, Human Genome, 2.1 Biological and endogenous factors (hrcs-rac), Estrogen, Female (mesh), Genome-Wide Association Study
Aging, 1117 Public Health and Health Services (for), receptor, Progesterone (mesh), Sustainable Development Goals, Medical Genetics and Genomics, Aging (rcdc), IMPUTATION, Estrone (mesh), /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being; name=SDG 3 - Good Health and Well-being, Aetiology, 32 Biomedical and Clinical Sciences (for-2020), Estrogen (mesh), Progesterone, Cancer, SDG 3, AOCS Group, 1112 Oncology and Carcinogenesis (for), Breast Cancer (rcdc), Premenopause (mesh), Oncology, Receptors, Estrogen, Public Health and Health Services, Alleles (mesh), Pregnanediol, Receptors, Progesterone, ABCTB Investigators, 610, /631/67/2324, progesterone, Article, SDG 3 - Good Health and Well-being, Clinical Research, 616, Genetics, 3211 Oncology and carcinogenesis (for-2020), Humans, Polymorphism, GENOME-WIDE ASSOCIATION, Alleles, Science & Technology, Genetics (rcdc), Cancer (hrcs-hc), /631/67/1347, Alleles; Breast Neoplasms; Case-Control Studies; Cytochrome P-450 CYP3A; Estrone; Female; Genome-Wide Association Study; Humans; Polymorphism, Single Nucleotide; Pregnanediol; Premenopause; Progesterone; Receptors, Estrogen; Receptors, Progesterone, Human Genome (rcdc), name=SDG 3 - Good Health and Well-being, 3211 Oncology and Carcinogenesis (for-2020), Premenopause, Oncology & Carcinogenesis (science-metrix), Case-Control Studies, CYP3A5, Women's Health (rcdc), Cytochrome P-450 CYP3A (mesh), Clinical Research (rcdc), Receptors, 2.1 Biological and endogenous factors, Cytochrome P-450 CYP3A, Cancer (rcdc), Humans (mesh), article, Single Nucleotide, estrone, Medicinsk genetik och genomik, /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being, kConFab Investigators, Genome-Wide Association Study (mesh), Female, Medical Genetics, Life Sciences & Biomedicine, Estrogen (rcdc), Single Nucleotide (mesh), Estrone, Oncology and Carcinogenesis, EMC OR-01, Breast Neoplasms, Pregnanediol (mesh), Polymorphism, Single Nucleotide, Case-Control Studies (mesh), NBCS Collaborators, 1117 Public Health and Health Services, Breast Neoplasms (mesh), 3211 Oncology and carcinogenesis, /631/67/68, Breast Cancer, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, breast, Medicinsk genetik, Human Genome, 2.1 Biological and endogenous factors (hrcs-rac), Estrogen, Female (mesh), Genome-Wide Association Study
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