TAMOXIFEN PHARMACODYNAMICS PATHWAY (PW:0000839)
Description
Tamoxifen (TAM, TX), an non-steroidal anti-estrogen, is one of the most commonly used drugs for the treatment and prevention of breast cancer. Estrogen is involved in the growth and development of breast cancers; estrogen mediated transcription is constitutively active in more than 50% of cases. Initially considered an antagonist, TAM is currently classified as a selective estrogen receptor modulator (SERM). It binds competitively to the estrogen receptors (ERs) acting as an antagonist in breast cancer cells and as a partial agonist in bone and the cardiovascular system. Members of the cytochrome P 450 (CYP) phase I and of phase II biotransformation pathways are responsible for the metabolism of the drug in human liver microsomes (HLM) and rat hepatic cytosol. TAM is extensively metabolized and both primary and secondary metabolites have higher potencies than the parent compound. Primary metabolites include alpha-OH-TAM and DMT or 4-OH-TAM of which alpha-OH-TAM can form toxic DNA adducts; DMT and 4-OH-TAM are further metabolized to the secondary metabolite endoxifen. Tamoxifen and its metabolites bind the estrogen receptors Esr1 and 2 (ER), albeit with somewhat different affinities. They block binding of estradiol to the receptors, prevent the conformational changes required for binding of coactivators and lead to preferential recruitment of corepressors such as Ncor1 and others. The suppressed transcriptional activity of the receptors results in suppressed tumor growth as genes regulated by estrogen are involved in proliferation, angiogenesis, anti-apoptosis, among others. However, the levels of ER coregulators, the phosphorylation of both receptors and coregulators and associated functional impacts, the non-genomic function of membrane-tethered ER receptors and cross-talk to growth factors, including over-expression of certain growth factor receptors such as Erbb2/Her2, can all contribute to tamoxifen resistance and promote survival of the breast cancer cell. For instance, Ncoa3 coactivator also known as Aib1 or Src3, is overexpressed and gene amplified in 64-65% and 5-10% of breast cancers, respectively. It is also to be noted that TAM can activate the membrane-tethered ERs in a manner analogous to estrogen ligands, thus accounting for its agonistic effects, including drug resistance. Endoxifen - the major metabolite responsible for the action of tamoxifen in vivo, appears to have differential effects on the two receptors. It stabilizes the beta receptor, promotes receptor heterodimerization and has a more inhibitory effect on the expression of target genes. On the other hand, endoxifen targets the alpha estrogen receptor for proteasomal degradation in breast cancer cells. Polymorphisms in several CYP phase I and UGT phase II enzymes of TAM metabolism impact on the relative abundance and availability of metabolites and subsequently on their effect on estrogen-induced breast cancer cell proliferation.
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Pathway Diagram:
Genes in Pathway:
G
Cyp2b3 cytochrome P450, family 2, subfamily b, polypeptide 3
ISO SMPDB SMP:00471
NCBI chr 1:81,652,762...81,732,153
G
Cyp2d4 cytochrome P450, family 2, subfamily d, polypeptide 4
ISO SMPDB SMP:00471
NCBI chr 7:113,882,584...113,891,754
G
Cyp3a2 cytochrome P450, family 3, subfamily a, polypeptide 2
ISO SMPDB SMP:00471
NCBI chr12:9,207,978...9,230,064
G
Cyp3a9 cytochrome P450, family 3, subfamily a, polypeptide 9
ISO SMPDB SMP:00471
NCBI chr12:16,806,222...16,846,428
G
Esr1 estrogen receptor 1
ISO SMPDB PMID:19629072 SMP:00471, RGD:5130191
NCBI chr 1:41,106,335...41,499,104
G
Esr2 estrogen receptor 2
ISO RGD
PMID:19629072 RGD:5130191
NCBI chr 6:94,858,438...94,909,630
G
Fmo1 flavin containing dimethylaniline monoxygenase 1
ISO SMPDB SMP:00471
NCBI chr13:75,182,184...75,214,439
G
Fmo3 flavin containing dimethylaniline monoxygenase 3
ISO SMPDB SMP:00471
NCBI chr13:75,309,367...75,334,915
G
Ncoa3 nuclear receptor coactivator 3
ISO RGD
PMID:16822624 RGD:5130718
NCBI chr 3:154,738,566...154,821,395
G
Ncor1 nuclear receptor co-repressor 1
ISO RGD
PMID:16822624 RGD:5130718
NCBI chr10:46,999,536...47,142,294
G
Ncor2 nuclear receptor co-repressor 2
ISO RGD
PMID:16822624 RGD:5130718
NCBI chr12:31,466,418...31,628,319
G
Phb2 prohibitin 2
ISO RGD
PMID:16822624 RGD:5130718
NCBI chr 4:157,517,662...157,522,268
G
Sult1a1 sulfotransferase family 1A member 1
ISO SMPDB SMP:00471
NCBI chr 1:181,272,022...181,276,750
G
Ugt1a5 UDP glucuronosyltransferase family 1 member A5
ISO SMPDB SMP:00471
NCBI chr 9:88,762,250...88,808,465
Pathway Gene Annotations
Disease Annotations Associated with Genes in the tamoxifen pharmacodynamics pathway
Cyp2b3 Acute Lymphoblastic Leukemia, with Lymphomatous Features , acute myeloid leukemia , autism spectrum disorder , Carpenter Syndrome 2 , Chemical and Drug Induced Liver Injury , cholestasis , congenital hypoplastic anemia , craniosynostosis , Diamond-Blackfan anemia , drug dependence , Drug Overdose , Efavirenz, Poor Metabolism of , end stage renal disease , Experimental Diabetes Mellitus , genetic disease , gliosarcoma , hepatocellular carcinoma , heroin dependence , human immunodeficiency virus infectious disease , maple syrup urine disease , Metabolic Side Effects of Drugs and Substances , neonatal abstinence syndrome , nicotine dependence , Tobacco Use Disorder , tuberculosis Cyp2d4 acute kidney failure , acute lymphoblastic leukemia , acute myeloid leukemia , alcohol dependence , Alzheimer's disease , amphetamine abuse , asthma , autism spectrum disorder , autoimmune hepatitis , basal ganglia disease , Bradycardia , Breast Neoplasms , Chemical and Drug Induced Liver Injury , Chronic Hepatitis C , cognitive disorder , Coma , common variable immunodeficiency 4 , Developmental Delay with Variable Intellectual Impairment and Behavioral Abnormalities , Drug Overdose , Drug-Induced Dyskinesia , Drug-Related Side Effects and Adverse Reactions , Dysmenorrhea , dystonia , epilepsy with generalized tonic-clonic seizures , Experimental Liver Cirrhosis , extrapyramidal and movement disease , genetic disease , head and neck squamous cell carcinoma , intellectual disability , interstitial nephritis , major depressive disorder , Manganese Poisoning , multiple myeloma , Muscle Rigidity , Occupational Diseases , opiate dependence , Parkinson's disease , Poor Drug Metabolism, CYP2D6-Related , Prenatal Exposure Delayed Effects , Prostatic Neoplasms , rhinitis , sexual health disorder , substance-related disorder , traumatic brain injury , Tremor , Weight Gain Cyp3a2 anxiety disorder , breast cancer , Breast Neoplasms , Chemical and Drug Induced Liver Injury , cholestasis , end stage renal disease , familial mediterranean fever , Familial Prostate Cancer , genetic disease , hepatitis C , Inflammation , osteosarcoma , ovarian carcinoma , pleomorphic xanthoastrocytoma , Prostatic Neoplasms , Subarachnoid Hemorrhage , Torsades de Pointes , type 2 diabetes mellitus , VITAMIN D-DEPENDENT RICKETS, TYPE 3 Cyp3a9 acute lymphoblastic leukemia , autism spectrum disorder , B-lymphoblastic leukemia/lymphoma , Chemotherapy-Induced Febrile Neutropenia , chronic myeloid leukemia , Drug-Induced Leukopenia , Drug-induced Neutropenia , essential hypertension , Experimental Liver Cirrhosis , genetic disease , kidney disease , myasthenia gravis , Myeloid Leukemia, Chronic-Phase , nephrosis , Pediatric Crohn's Disease , pleomorphic xanthoastrocytoma , Prostatic Neoplasms , Reperfusion Injury , thrombosis , toxic encephalopathy Esr1 adenocarcinoma , Alzheimer's disease , Animal Disease Models , Animal Mammary Neoplasms , arteriosclerosis , arthrogryposis multiplex congenita-3 , atherosclerosis , autosomal dominant Emery-Dreifuss muscular dystrophy 4 , autosomal recessive spinocerebellar ataxia 8 , bone disease , Bone Fractures , breast cancer , Breast Cancer, Familial , breast carcinoma , Breast Neoplasms , Bronchial Hyperreactivity , carcinoma , cataract 33 , cerebellar ataxia , chromosome 6q24-q25 deletion syndrome , Chronic Periodontitis , coronary artery disease , cryptorchidism , Diabetic Nephropathies , Disease Progression , Emery-Dreifuss muscular dystrophy , Endometrial Neoplasms , Endometrioid Carcinomas , endometriosis , Estrogen Resistance , Experimental Arthritis , Experimental Diabetes Mellitus , Experimental Liver Neoplasms , Experimental Mammary Neoplasms , Female Infertility , Female Urogenital Diseases , Feminization , genetic disease , Genetic Predisposition to Disease , glomerulonephritis , Hand Osteoarthritis , Hemorrhagic Shock , hepatocellular carcinoma , Hyperalgesia , idiopathic pulmonary fibrosis , in situ carcinoma , infertility , Knee Osteoarthritis , leiomyoma , leukemia , Leydig cell tumor , Liver Neoplasms , Lung Neoplasms , lung non-small cell carcinoma , lymphangioleiomyomatosis , macular degeneration , male infertility , malignant astrocytoma , melanoma , Mesothelioma , Metabolic Bone Diseases , migraine , mitochondrial metabolism disease , Musculoskeletal Pain , myocardial infarction , Myocardial Reperfusion Injury , Neoplasm Invasiveness , Neoplasm Metastasis , Neoplasm Recurrence, Local , Neoplastic Cell Transformation , neuroblastoma , obesity , oligospermia , osteoarthritis , Osteoarthritis, Hip , osteoporosis , Osteoporotic Fractures , ovarian cancer , Parkinsonism , peritonitis , pleurisy , Postmenopausal Osteoporosis , prostate cancer , prostate carcinoma in situ , prostatic hypertrophy , Prostatic Neoplasms , pulmonary hypertension , Spinal Cord Injuries , Spinal Fractures , sporadic breast cancer , Subarachnoid Hemorrhage , substance-induced psychosis , systemic scleroderma , transient cerebral ischemia , type 2 diabetes mellitus , urinary bladder cancer , Urination Disorders , Varicose Ulcer , vitiligo , Vulvar Lichen Sclerosus Esr2 adenocarcinoma , adenoma , alopecia , Alzheimer's disease , Animal Mammary Neoplasms , anxiety disorder , aortic valve stenosis , asthma , atherosclerosis , atrial fibrillation , Blast Crisis , brain ischemia , breast cancer , Breast Neoplasms , carcinoma , Cardiac Arrhythmias , Cocaine-Related Disorders , Cognitive Dysfunction , colitis , colon cancer , colorectal cancer , Colorectal Neoplasms , contact dermatitis , coronary artery disease , Coronary Disease , COVID-19 , Crohn's disease , cystitis , Deafness , depressive disorder , Endometrial Neoplasms , endometriosis , Experimental Arthritis , Experimental Autoimmune Encephalomyelitis , Experimental Mammary Neoplasms , Experimental Melanoma , Female Infertility , genetic disease , glomerulosclerosis , Graves' disease , Hand Osteoarthritis , Hashimoto Disease , Hearing Loss , Hemorrhagic Shock , Hot Flashes , Hyperalgesia , hypertension , hypospadias , in situ carcinoma , inflammatory bowel disease , interstitial cystitis , Knee Osteoarthritis , Left Ventricular Hypertrophy , Lithiasis , Lung Injury , malignant astrocytoma , medulloblastoma , melanoma , myasthenia gravis , myeloid leukemia , Myocardial Reperfusion Injury , Neoplastic Cell Transformation , obesity , osteoarthritis , osteoporosis , Osteoporotic Fractures , ovarian dysgenesis 8 , Parkinson's disease , peritonitis , Pituitary Neoplasms , Postmenopausal Osteoporosis , pre-eclampsia , primary open angle glaucoma , prostate cancer , prostate carcinoma in situ , prostatic hypertrophy , Prostatic Neoplasms , pulmonary hypertension , retinal degeneration , rheumatoid arthritis , Sepsis , Spinal Cord Injuries , Splenomegaly , Stroke , systemic lupus erythematosus , systemic scleroderma , transient cerebral ischemia , transitional cell carcinoma , ulcerative colitis , urinary bladder cancer , Urination Disorders , Varicose Ulcer , Vulvar Lichen Sclerosus Fmo1 1q24 Deletion Syndrome , amyotrophic lateral sclerosis type 1 , autism spectrum disorder , Experimental Liver Cirrhosis , gastrointestinal stromal tumor , genetic disease , parathyroid carcinoma Fmo3 1q24 Deletion Syndrome , autism spectrum disorder , Chemical and Drug Induced Liver Injury , familial adenomatous polyposis , gastrointestinal stromal tumor , genetic disease , hypertension , inherited metabolic disorder , parathyroid carcinoma , trimethylaminuria Ncoa3 adenocarcinoma , Bone Neoplasms , breast cancer , breast carcinoma , Breast Neoplasms , focal epilepsy , genetic disease , leukemia , lung non-small cell carcinoma , malignant astrocytoma , obesity , prostate cancer , Prostatic Neoplasms , sensorineural hearing loss , squamous cell carcinoma Ncor1 Acute-Phase Reaction , anxiety disorder , autistic disorder , Breast Cancer, Familial , Breast Neoplasms , Developmental Disabilities , endometriosis , genetic disease , glioblastoma , Huntington's disease , hypothyroidism , Liver Neoplasms , mitochondrial complex III deficiency nuclear type 1 , mitochondrial complex III deficiency nuclear type 2 , Neonatal Hyperbilirubinemia , polycystic ovary syndrome , Prostatic Neoplasms , transitional cell carcinoma , urinary bladder cancer Ncor2 breast cancer , endometrial carcinoma , Experimental Liver Cirrhosis , genetic disease , multiple myeloma , myelofibrosis , osteoarthritis , Prostatic Neoplasms Phb2 Brain Injuries , developmental and epileptic encephalopathy 21 , genetic disease , Hyperphosphatemic Familial Tumoral Calcinosis 1 , Klippel-Feil syndrome 3 , lymphoproliferative syndrome 2 , peroxisome biogenesis disorder 2B , Temtamy syndrome Sult1a1 benign neoplasm , breast cancer , Breast Neoplasms , chromosome 16p11.2 deletion syndrome, 220-kb , Chromosome Aberrations , Colonic Neoplasms , Colorectal Neoplasms , COVID-19 , endometrial cancer , Endometrial Neoplasms , esophagus squamous cell carcinoma , genetic disease , Genomic Instability , Hypotension , lung adenocarcinoma , lung cancer , lung squamous cell carcinoma , Myocardial Ischemia , neural tube defect , neuronal ceroid lipofuscinosis , Ovarian Neoplasms , prostate cancer , Prostatic Neoplasms , Recurrence , schizophrenia , stomach cancer , urinary bladder cancer , Urologic Neoplasms Ugt1a5 bilirubin metabolic disorder , celiac disease , Crigler Najjar Syndrome, Type 2 , Crigler-Najjar syndrome , genetic disease , Gilbert syndrome , Hyperbilirubinemia, Transient Familial Neonatal , Joubert syndrome 22 , Perlman syndrome
1q24 Deletion Syndrome Fmo1 , Fmo3 acute kidney failure Cyp2d4 acute lymphoblastic leukemia Cyp2d4 , Cyp3a9 Acute Lymphoblastic Leukemia, with Lymphomatous Features Cyp2b3 acute myeloid leukemia Cyp2b3 , Cyp2d4 Acute-Phase Reaction Ncor1 adenocarcinoma Esr1 , Esr2 , Ncoa3 adenoma Esr2 alcohol dependence Cyp2d4 alopecia Esr2 Alzheimer's disease Cyp2d4 , Esr1 , Esr2 amphetamine abuse Cyp2d4 amyotrophic lateral sclerosis type 1 Fmo1 Animal Disease Models Esr1 Animal Mammary Neoplasms Esr1 , Esr2 anxiety disorder Cyp3a2 , Esr2 , Ncor1 aortic valve stenosis Esr2 arteriosclerosis Esr1 arthrogryposis multiplex congenita-3 Esr1 asthma Cyp2d4 , Esr2 atherosclerosis Esr1 , Esr2 atrial fibrillation Esr2 autism spectrum disorder Cyp2b3 , Cyp2d4 , Cyp3a9 , Fmo1 , Fmo3 autistic disorder Ncor1 autoimmune hepatitis Cyp2d4 autosomal dominant Emery-Dreifuss muscular dystrophy 4 Esr1 autosomal recessive spinocerebellar ataxia 8 Esr1 B-lymphoblastic leukemia/lymphoma Cyp3a9 basal ganglia disease Cyp2d4 benign neoplasm Sult1a1 bilirubin metabolic disorder Ugt1a5 Blast Crisis Esr2 bone disease Esr1 Bone Fractures Esr1 Bone Neoplasms Ncoa3 Bradycardia Cyp2d4 Brain Injuries Phb2 brain ischemia Esr2 breast cancer Cyp3a2 , Esr1 , Esr2 , Ncoa3 , Ncor2 , Sult1a1 Breast Cancer, Familial Esr1 , Ncor1 breast carcinoma Esr1 , Ncoa3 Breast Neoplasms Cyp2d4 , Cyp3a2 , Esr1 , Esr2 , Ncoa3 , Ncor1 , Sult1a1 Bronchial Hyperreactivity Esr1 carcinoma Esr1 , Esr2 Cardiac Arrhythmias Esr2 Carpenter Syndrome 2 Cyp2b3 cataract 33 Esr1 celiac disease Ugt1a5 cerebellar ataxia Esr1 Chemical and Drug Induced Liver Injury Cyp2b3 , Cyp2d4 , Cyp3a2 , Fmo3 Chemotherapy-Induced Febrile Neutropenia Cyp3a9 cholestasis Cyp2b3 , Cyp3a2 chromosome 16p11.2 deletion syndrome, 220-kb Sult1a1 chromosome 6q24-q25 deletion syndrome Esr1 Chromosome Aberrations Sult1a1 Chronic Hepatitis C Cyp2d4 chronic myeloid leukemia Cyp3a9 Chronic Periodontitis Esr1 Cocaine-Related Disorders Esr2 cognitive disorder Cyp2d4 Cognitive Dysfunction Esr2 colitis Esr2 colon cancer Esr2 Colonic Neoplasms Sult1a1 colorectal cancer Esr2 Colorectal Neoplasms Esr2 , Sult1a1 Coma Cyp2d4 common variable immunodeficiency 4 Cyp2d4 congenital hypoplastic anemia Cyp2b3 contact dermatitis Esr2 coronary artery disease Esr1 , Esr2 Coronary Disease Esr2 COVID-19 Esr2 , Sult1a1 craniosynostosis Cyp2b3 Crigler Najjar Syndrome, Type 2 Ugt1a5 Crigler-Najjar syndrome Ugt1a5 Crohn's disease Esr2 cryptorchidism Esr1 cystitis Esr2 Deafness Esr2 depressive disorder Esr2 developmental and epileptic encephalopathy 21 Phb2 Developmental Delay with Variable Intellectual Impairment and Behavioral Abnormalities Cyp2d4 Developmental Disabilities Ncor1 Diabetic Nephropathies Esr1 Diamond-Blackfan anemia Cyp2b3 Disease Progression Esr1 drug dependence Cyp2b3 Drug Overdose Cyp2b3 , Cyp2d4 Drug-Induced Dyskinesia Cyp2d4 Drug-Induced Leukopenia Cyp3a9 Drug-induced Neutropenia Cyp3a9 Drug-Related Side Effects and Adverse Reactions Cyp2d4 Dysmenorrhea Cyp2d4 dystonia Cyp2d4 Efavirenz, Poor Metabolism of Cyp2b3 Emery-Dreifuss muscular dystrophy Esr1 end stage renal disease Cyp2b3 , Cyp3a2 endometrial cancer Sult1a1 endometrial carcinoma Ncor2 Endometrial Neoplasms Esr1 , Esr2 , Sult1a1 Endometrioid Carcinomas Esr1 endometriosis Esr1 , Esr2 , Ncor1 epilepsy with generalized tonic-clonic seizures Cyp2d4 esophagus squamous cell carcinoma Sult1a1 essential hypertension Cyp3a9 Estrogen Resistance Esr1 Experimental Arthritis Esr1 , Esr2 Experimental Autoimmune Encephalomyelitis Esr2 Experimental Diabetes Mellitus Cyp2b3 , Esr1 Experimental Liver Cirrhosis Cyp2d4 , Cyp3a9 , Fmo1 , Ncor2 Experimental Liver Neoplasms Esr1 Experimental Mammary Neoplasms Esr1 , Esr2 Experimental Melanoma Esr2 extrapyramidal and movement disease Cyp2d4 familial adenomatous polyposis Fmo3 familial mediterranean fever Cyp3a2 Familial Prostate Cancer Cyp3a2 Female Infertility Esr1 , Esr2 Female Urogenital Diseases Esr1 Feminization Esr1 focal epilepsy Ncoa3 gastrointestinal stromal tumor Fmo1 , Fmo3 genetic disease Cyp2b3 , Cyp2d4 , Cyp3a2 , Cyp3a9 , Esr1 , Esr2 , Fmo1 , Fmo3 , Ncoa3 , Ncor1 , Ncor2 , Phb2 , Sult1a1 , Ugt1a5 Genetic Predisposition to Disease Esr1 Genomic Instability Sult1a1 Gilbert syndrome Ugt1a5 glioblastoma Ncor1 gliosarcoma Cyp2b3 glomerulonephritis Esr1 glomerulosclerosis Esr2 Graves' disease Esr2 Hand Osteoarthritis Esr1 , Esr2 Hashimoto Disease Esr2 head and neck squamous cell carcinoma Cyp2d4 Hearing Loss Esr2 Hemorrhagic Shock Esr1 , Esr2 hepatitis C Cyp3a2 hepatocellular carcinoma Cyp2b3 , Esr1 heroin dependence Cyp2b3 Hot Flashes Esr2 human immunodeficiency virus infectious disease Cyp2b3 Huntington's disease Ncor1 Hyperalgesia Esr1 , Esr2 Hyperbilirubinemia, Transient Familial Neonatal Ugt1a5 Hyperphosphatemic Familial Tumoral Calcinosis 1 Phb2 hypertension Esr2 , Fmo3 hypospadias Esr2 Hypotension Sult1a1 hypothyroidism Ncor1 idiopathic pulmonary fibrosis Esr1 in situ carcinoma Esr1 , Esr2 infertility Esr1 Inflammation Cyp3a2 inflammatory bowel disease Esr2 inherited metabolic disorder Fmo3 intellectual disability Cyp2d4 interstitial cystitis Esr2 interstitial nephritis Cyp2d4 Joubert syndrome 22 Ugt1a5 kidney disease Cyp3a9 Klippel-Feil syndrome 3 Phb2 Knee Osteoarthritis Esr1 , Esr2 Left Ventricular Hypertrophy Esr2 leiomyoma Esr1 leukemia Esr1 , Ncoa3 Leydig cell tumor Esr1 Lithiasis Esr2 Liver Neoplasms Esr1 , Ncor1 lung adenocarcinoma Sult1a1 lung cancer Sult1a1 Lung Injury Esr2 Lung Neoplasms Esr1 lung non-small cell carcinoma Esr1 , Ncoa3 lung squamous cell carcinoma Sult1a1 lymphangioleiomyomatosis Esr1 lymphoproliferative syndrome 2 Phb2 macular degeneration Esr1 major depressive disorder Cyp2d4 male infertility Esr1 malignant astrocytoma Esr1 , Esr2 , Ncoa3 Manganese Poisoning Cyp2d4 maple syrup urine disease Cyp2b3 medulloblastoma Esr2 melanoma Esr1 , Esr2 Mesothelioma Esr1 Metabolic Bone Diseases Esr1 Metabolic Side Effects of Drugs and Substances Cyp2b3 migraine Esr1 mitochondrial complex III deficiency nuclear type 1 Ncor1 mitochondrial complex III deficiency nuclear type 2 Ncor1 mitochondrial metabolism disease Esr1 multiple myeloma Cyp2d4 , Ncor2 Muscle Rigidity Cyp2d4 Musculoskeletal Pain Esr1 myasthenia gravis Cyp3a9 , Esr2 myelofibrosis Ncor2 myeloid leukemia Esr2 Myeloid Leukemia, Chronic-Phase Cyp3a9 myocardial infarction Esr1 Myocardial Ischemia Sult1a1 Myocardial Reperfusion Injury Esr1 , Esr2 neonatal abstinence syndrome Cyp2b3 Neonatal Hyperbilirubinemia Ncor1 Neoplasm Invasiveness Esr1 Neoplasm Metastasis Esr1 Neoplasm Recurrence, Local Esr1 Neoplastic Cell Transformation Esr1 , Esr2 nephrosis Cyp3a9 neural tube defect Sult1a1 neuroblastoma Esr1 neuronal ceroid lipofuscinosis Sult1a1 nicotine dependence Cyp2b3 obesity Esr1 , Esr2 , Ncoa3 Occupational Diseases Cyp2d4 oligospermia Esr1 opiate dependence Cyp2d4 osteoarthritis Esr1 , Esr2 , Ncor2 Osteoarthritis, Hip Esr1 osteoporosis Esr1 , Esr2 Osteoporotic Fractures Esr1 , Esr2 osteosarcoma Cyp3a2 ovarian cancer Esr1 ovarian carcinoma Cyp3a2 ovarian dysgenesis 8 Esr2 Ovarian Neoplasms Sult1a1 parathyroid carcinoma Fmo1 , Fmo3 Parkinson's disease Cyp2d4 , Esr2 Parkinsonism Esr1 Pediatric Crohn's Disease Cyp3a9 peritonitis Esr1 , Esr2 Perlman syndrome Ugt1a5 peroxisome biogenesis disorder 2B Phb2 Pituitary Neoplasms Esr2 pleomorphic xanthoastrocytoma Cyp3a2 , Cyp3a9 pleurisy Esr1 polycystic ovary syndrome Ncor1 Poor Drug Metabolism, CYP2D6-Related Cyp2d4 Postmenopausal Osteoporosis Esr1 , Esr2 pre-eclampsia Esr2 Prenatal Exposure Delayed Effects Cyp2d4 primary open angle glaucoma Esr2 prostate cancer Esr1 , Esr2 , Ncoa3 , Sult1a1 prostate carcinoma in situ Esr1 , Esr2 prostatic hypertrophy Esr1 , Esr2 Prostatic Neoplasms Cyp2d4 , Cyp3a2 , Cyp3a9 , Esr1 , Esr2 , Ncoa3 , Ncor1 , Ncor2 , Sult1a1 pulmonary hypertension Esr1 , Esr2 Recurrence Sult1a1 Reperfusion Injury Cyp3a9 retinal degeneration Esr2 rheumatoid arthritis Esr2 rhinitis Cyp2d4 schizophrenia Sult1a1 sensorineural hearing loss Ncoa3 Sepsis Esr2 sexual health disorder Cyp2d4 Spinal Cord Injuries Esr1 , Esr2 Spinal Fractures Esr1 Splenomegaly Esr2 sporadic breast cancer Esr1 squamous cell carcinoma Ncoa3 stomach cancer Sult1a1 Stroke Esr2 Subarachnoid Hemorrhage Cyp3a2 , Esr1 substance-induced psychosis Esr1 substance-related disorder Cyp2d4 systemic lupus erythematosus Esr2 systemic scleroderma Esr1 , Esr2 Temtamy syndrome Phb2 thrombosis Cyp3a9 Tobacco Use Disorder Cyp2b3 Torsades de Pointes Cyp3a2 toxic encephalopathy Cyp3a9 transient cerebral ischemia Esr1 , Esr2 transitional cell carcinoma Esr2 , Ncor1 traumatic brain injury Cyp2d4 Tremor Cyp2d4 trimethylaminuria Fmo3 tuberculosis Cyp2b3 type 2 diabetes mellitus Cyp3a2 , Esr1 ulcerative colitis Esr2 urinary bladder cancer Esr1 , Esr2 , Ncor1 , Sult1a1 Urination Disorders Esr1 , Esr2 Urologic Neoplasms Sult1a1 Varicose Ulcer Esr1 , Esr2 VITAMIN D-DEPENDENT RICKETS, TYPE 3 Cyp3a2 vitiligo Esr1 Vulvar Lichen Sclerosus Esr1 , Esr2 Weight Gain Cyp2d4
