Evaluation of vitamin D biosynthesis and pathway target genes reveals UGT2A1/2 and EGFR polymorphisms associated with epithelial ovarian cancer in African American Women
Abstract An association between genetic variants in the vitamin D receptor (VDR) gene and epithelial ovarian cancer (EOC) was previously reported in women of African ancestry (AA). We sought to examine associations between genetic variants in VDR and additional genes from vitamin D biosynthesis and...
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| Format: | Article |
| Language: | English |
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Wiley
2019-05-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.1996 |
| _version_ | 1797236893269622784 |
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| author | Delores J. Grant Ani Manichaikul Anthony J. Alberg Elisa V. Bandera Jill Barnholtz‐Sloan Melissa Bondy Michele L. Cote Ellen Funkhouser Patricia G. Moorman Lauren C. Peres Edward S. Peters Ann G. Schwartz Paul D. Terry Xin‐Qun Wang Temitope O. Keku Cathrine Hoyo Andrew Berchuck Dale P. Sandler Jack A. Taylor Katie M. O’Brien Digna R. Velez Edwards Todd L. Edwards Alicia Beeghly‐Fadiel Nicolas Wentzensen Celeste Leigh Pearce Anna H. Wu Alice S. Whittemore Valerie McGuire Weiva Sieh Joseph H. Rothstein Francesmary Modugno Roberta Ness Kirsten Moysich Mary Anne Rossing Jennifer A. Doherty Thomas A. Sellers Jennifer B. Permuth‐Way Alvaro N. Monteiro Douglas A. Levine Veronica Wendy Setiawan Christopher A. Haiman Loic LeMarchand Lynne R. Wilkens Beth Y. Karlan Usha Menon Susan Ramus Simon Gayther Aleksandra Gentry‐Maharaj Kathryn L. Terry Daniel W. Cramer Ellen L. Goode Melissa C. Larson Scott H. Kaufmann Rikki Cannioto Kunle Odunsi John L. Etter Ruea‐Yea Huang Marcus Q. Bernardini Alicia A. Tone Taymaa May Marc T. Goodman Pamela J. Thompson Michael E. Carney Shelley S. Tworoger Elizabeth M. Poole Diether Lambrechts Ignace Vergote Adriaan Vanderstichele Els Van Nieuwenhuysen Hoda Anton‐Culver Argyrios Ziogas James D. Brenton Line Bjorge Helga B. Salvensen Lambertus A. Kiemeney Leon F. A. G. Massuger Tanja Pejovic Amanda Bruegl Melissa Moffitt Linda Cook Nhu D. Le Angela Brooks‐Wilson Linda E. Kelemen Paul D.P. Pharoah Honglin Song Ian Campbell Diana Eccles Anna DeFazio Catherine J. Kennedy Joellen M. Schildkraut |
| author_facet | Delores J. Grant Ani Manichaikul Anthony J. Alberg Elisa V. Bandera Jill Barnholtz‐Sloan Melissa Bondy Michele L. Cote Ellen Funkhouser Patricia G. Moorman Lauren C. Peres Edward S. Peters Ann G. Schwartz Paul D. Terry Xin‐Qun Wang Temitope O. Keku Cathrine Hoyo Andrew Berchuck Dale P. Sandler Jack A. Taylor Katie M. O’Brien Digna R. Velez Edwards Todd L. Edwards Alicia Beeghly‐Fadiel Nicolas Wentzensen Celeste Leigh Pearce Anna H. Wu Alice S. Whittemore Valerie McGuire Weiva Sieh Joseph H. Rothstein Francesmary Modugno Roberta Ness Kirsten Moysich Mary Anne Rossing Jennifer A. Doherty Thomas A. Sellers Jennifer B. Permuth‐Way Alvaro N. Monteiro Douglas A. Levine Veronica Wendy Setiawan Christopher A. Haiman Loic LeMarchand Lynne R. Wilkens Beth Y. Karlan Usha Menon Susan Ramus Simon Gayther Aleksandra Gentry‐Maharaj Kathryn L. Terry Daniel W. Cramer Ellen L. Goode Melissa C. Larson Scott H. Kaufmann Rikki Cannioto Kunle Odunsi John L. Etter Ruea‐Yea Huang Marcus Q. Bernardini Alicia A. Tone Taymaa May Marc T. Goodman Pamela J. Thompson Michael E. Carney Shelley S. Tworoger Elizabeth M. Poole Diether Lambrechts Ignace Vergote Adriaan Vanderstichele Els Van Nieuwenhuysen Hoda Anton‐Culver Argyrios Ziogas James D. Brenton Line Bjorge Helga B. Salvensen Lambertus A. Kiemeney Leon F. A. G. Massuger Tanja Pejovic Amanda Bruegl Melissa Moffitt Linda Cook Nhu D. Le Angela Brooks‐Wilson Linda E. Kelemen Paul D.P. Pharoah Honglin Song Ian Campbell Diana Eccles Anna DeFazio Catherine J. Kennedy Joellen M. Schildkraut |
| author_sort | Delores J. Grant |
| collection | DOAJ |
| description | Abstract An association between genetic variants in the vitamin D receptor (VDR) gene and epithelial ovarian cancer (EOC) was previously reported in women of African ancestry (AA). We sought to examine associations between genetic variants in VDR and additional genes from vitamin D biosynthesis and pathway targets (EGFR, UGT1A, UGT2A1/2, UGT2B, CYP3A4/5, CYP2R1, CYP27B1, CYP24A1, CYP11A1, and GC). Genotyping was performed using the custom‐designed 533,631 SNP Illumina OncoArray with imputation to the 1,000 Genomes Phase 3 v5 reference set in 755 EOC cases, including 537 high‐grade serous (HGSOC), and 1,235 controls. All subjects are of African ancestry (AA). Logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI). We further evaluated statistical significance of selected SNPs using the Bayesian False Discovery Probability (BFDP). A significant association with EOC was identified in the UGT2A1/2 region for the SNP rs10017134 (per allele OR = 1.4, 95% CI = 1.2‐1.7, P = 1.2 × 10−6, BFDP = 0.02); and an association with HGSOC was identified in the EGFR region for the SNP rs114972508 (per allele OR = 2.3, 95% CI = 1.6‐3.4, P = 1.6 × 10−5, BFDP = 0.29) and in the UGT2A1/2 region again for rs1017134 (per allele OR = 1.4, 95% CI = 1.2‐1.7, P = 2.3 × 10−5, BFDP = 0.23). Genetic variants in the EGFR and UGT2A1/2 may increase susceptibility of EOC in AA women. Future studies to validate these findings are warranted. Alterations in EGFR and UGT2A1/2 could perturb enzyme efficacy, proliferation in ovaries, impact and mark susceptibility to EOC. |
| first_indexed | 2024-04-24T17:11:05Z |
| format | Article |
| id | doaj.art-e1138d0ca72749ca892bbfadf3342940 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-24T17:11:05Z |
| publishDate | 2019-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-e1138d0ca72749ca892bbfadf33429402024-03-28T10:30:36ZengWileyCancer Medicine2045-76342019-05-01852503251310.1002/cam4.1996Evaluation of vitamin D biosynthesis and pathway target genes reveals UGT2A1/2 and EGFR polymorphisms associated with epithelial ovarian cancer in African American WomenDelores J. Grant0Ani Manichaikul1Anthony J. Alberg2Elisa V. Bandera3Jill Barnholtz‐Sloan4Melissa Bondy5Michele L. Cote6Ellen Funkhouser7Patricia G. Moorman8Lauren C. Peres9Edward S. Peters10Ann G. Schwartz11Paul D. Terry12Xin‐Qun Wang13Temitope O. Keku14Cathrine Hoyo15Andrew Berchuck16Dale P. Sandler17Jack A. Taylor18Katie M. O’Brien19Digna R. Velez Edwards20Todd L. Edwards21Alicia Beeghly‐Fadiel22Nicolas Wentzensen23Celeste Leigh Pearce24Anna H. Wu25Alice S. Whittemore26Valerie McGuire27Weiva Sieh28Joseph H. Rothstein29Francesmary Modugno30Roberta Ness31Kirsten Moysich32Mary Anne Rossing33Jennifer A. Doherty34Thomas A. Sellers35Jennifer B. Permuth‐Way36Alvaro N. Monteiro37Douglas A. Levine38Veronica Wendy Setiawan39Christopher A. Haiman40Loic LeMarchand41Lynne R. Wilkens42Beth Y. Karlan43Usha Menon44Susan Ramus45Simon Gayther46Aleksandra Gentry‐Maharaj47Kathryn L. Terry48Daniel W. Cramer49Ellen L. Goode50Melissa C. Larson51Scott H. Kaufmann52Rikki Cannioto53Kunle Odunsi54John L. Etter55Ruea‐Yea Huang56Marcus Q. Bernardini57Alicia A. Tone58Taymaa May59Marc T. Goodman60Pamela J. Thompson61Michael E. Carney62Shelley S. Tworoger63Elizabeth M. Poole64Diether Lambrechts65Ignace Vergote66Adriaan Vanderstichele67Els Van Nieuwenhuysen68Hoda Anton‐Culver69Argyrios Ziogas70James D. Brenton71Line Bjorge72Helga B. Salvensen73Lambertus A. Kiemeney74Leon F. A. G. Massuger75Tanja Pejovic76Amanda Bruegl77Melissa Moffitt78Linda Cook79Nhu D. Le80Angela Brooks‐Wilson81Linda E. Kelemen82Paul D.P. Pharoah83Honglin Song84Ian Campbell85Diana Eccles86Anna DeFazio87Catherine J. Kennedy88Joellen M. Schildkraut89Department of Biological and Biomedical Sciences, Cancer Research Program JLC‐Biomedical/Biotechnology Research Institute, North Carolina Central University Durham North CarolinaCenter for Public Health Genomics University of Virginia Charlottesville VirginiaDepartment of Epidemiology and Biostatistics, Arnold School of Public Health University of South Carolina Columbia South CarolinaDepartment of Population Science Rutgers Cancer Institute of New Jersey New Brunswick New JerseyCase Comprehensive Cancer Center Case Western Reserve University School of Medicine Cleveland OhioCancer Prevention and Population Sciences Program Baylor College of Medicine Houston TexasDepartment of Oncology and the Karmanos Cancer Institute Population Studies and Disparities Research Program Wayne State University School of Medicine Detroit MichiganDivision of Preventive Medicine University of Alabama at Birmingham Birmingham AlabamaDepartment of Community and Family Medicine Duke University Medical Center Durham North CarolinaCenter for Public Health Genomics University of Virginia Charlottesville VirginiaEpidemiology Program Louisiana State University Health Sciences Center School of Public Health New Orleans LouisisanaDepartment of Oncology and the Karmanos Cancer Institute Population Studies and Disparities Research Program Wayne State University School of Medicine Detroit MichiganDepartment of Medicine University of Tennessee Medical Center – Knoxville Knoxville TennesseeDepartment of Public Health Sciences University of Virginia Charlottesville VirginiaDepartments of Medicine and Nutrition, Division of Gastroenterology and Hepatology University of North Carolina at Chapel Hill Chapel Hill North CarolinaDepartment of Biological Sciences North Carolina State University Raleigh North CarolinaDepartment of Obstetrics and Gynecology Duke University Medical Center Durham North CarolinaEpidemiology Branch, Division of Intramural Research National Institute of Environmental Health Sciences, National Institutes of Health Research Triangle Park North CarolinaEpidemiology Branch, Division of Intramural Research National Institute of Environmental Health Sciences, National Institutes of Health Research Triangle Park North CarolinaEpidemiology Branch, Division of Intramural Research National Institute of Environmental Health Sciences, National Institutes of Health Research Triangle Park North CarolinaVanderbilt Epidemiology Center, Center for Human Genetics Research, Department of Obstetrics and Gynecology Vanderbilt University Medical Center Nashville TennesseeDivision of Epidemiology, Center for Human Genetics Research, Department of Medicine Vanderbilt University Medical Center Nashville TennesseeDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center Institute for Medicine and Public Health, Vanderbilt University Medical Center Nashville TennesseeDivision of Cancer Epidemiology and Genetics National Cancer Institute Bethesda MarylandDepartment of Epidemiology University of Michigan School of Public Health Ann Arbor MichiganDepartment of Preventive Medicine, Keck School of Medicine University of Southern California Norris Comprehensive Cancer Center Los Angeles CaliforniaDepartment of Health Research and Policy Stanford University School of Medicine Stanford CaliforniaDepartment of Health Research and Policy Stanford University School of Medicine Stanford CaliforniaDepartment of Population Health Science and Policy Icahn School of Medicine at Mount Sinai New York New YorkDepartment of Population Health Science and Policy Icahn School of Medicine at Mount Sinai New York New YorkDivision of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences University of Pittsburgh School of Medicine Pittsburgh PennsylvaniaThe University of Texas School of Public Health Houston TexasDepartment of Cancer Prevention and Control Roswell Park Cancer Institute Buffalo New YorkProgram in Epidemiology, Division of Public Health Sciences Fred Hutchinson Cancer Research Center Seattle WashingtonDepartment of Population Health Sciences Huntsman Cancer Institute, University of Utah Salt Lake City, UtahDepartment of Cancer Epidemiology Moffitt Cancer Center Tampa FloridaDepartment of Cancer Epidemiology Moffitt Cancer Center Tampa FloridaDepartment of Cancer Epidemiology Moffitt Cancer Center Tampa FloridaGynecology Service, Department of Surgery Memorial Sloan Kettering Cancer Center New York New YorkUniversity of Southern California Norris Comprehensive Cancer Center Los Angeles CaliforniaUniversity of Southern California Norris Comprehensive Cancer Center Los Angeles CaliforniaUniversity of Hawaii Cancer Center Honolulu HawaiiCancer Epidemiology Program University of Hawaii Cancer Center HawaiiWomen's Cancer Program Samuel Oschin Comprehensive Cancer Institute, Cedars‐Sinai Medical Center Los Angeles CaliforniaMRC CTU at UCL, Institute of Clinical Trials and Methodology University College London London UKSchool of Women's and Children's Health University of New South Wales New South Wales AustraliaCenter for Cancer Prevention and Translational Genomics Samuel Oschin Comprehensive Cancer Institute, Cedars‐Sinai Medical Center Los Angeles CaliforniaMRC CTU at UCL, Institute of Clinical Trials and Methodology University College London London UKObstetrics and Gynecology Epidemiology Center Brigham and Women's Hospital Boston MassachusettsObstetrics and Gynecology Epidemiology Center Brigham and Women's Hospital Boston MassachusettsDepartment of Health Science Research, Division of Epidemiology Mayo Clinic Rochester MinnesotaDepartment of Health Science Research, Division of Biomedical Statistics and Informatics Mayo Clinic Rochester MinnesotaDepartments of Medicine and Pharmacology Mayo Clinic Rochester MinnesotaCancer Pathology & Prevention, Division of Cancer Prevention and Population Sciences Roswell Park Cancer Institute Buffalo New YorkDepartment of Gynecological Oncology Roswell Park Cancer Institute Buffalo New YorkDepartment of Cancer Prevention and Control Roswell Park Cancer Institute Buffalo New YorkCenter For Immunotherapy Roswell Park Cancer Institute Buffalo New YorkDivision of Gynecologic Oncology Princess Margaret Hospital, University Health Network Toronto Ontario CanadaDivision of Gynecologic Oncology Princess Margaret Hospital, University Health Network Toronto Ontario CanadaDivision of Gynecologic Oncology Princess Margaret Hospital, University Health Network Toronto Ontario CanadaCancer Prevention and Control Samuel Oschin Comprehensive Cancer Institute, Cedars‐Sinai Medical Center Los Angeles CaliforniaCancer Prevention and Control Samuel Oschin Comprehensive Cancer Institute, Cedars‐Sinai Medical Center Los Angeles CaliforniaDepartment of Obstetrics and Gynecology John A. Burns School of Medicine, University of Hawaii Honolulu HawaiiChanning Division of Network Medicine Brigham and Women's Hospital and Harvard Medical School Boston MassachusettsBiostatistics, Sanofi Genzyme Boston MassachusettsVesalius Research Center, VIB Leuven BelgiumDivision of Gynecologic Oncology, Department of Obstetrics and Gynaecology and Leuven Cancer Institute University Hospitals Leuven Leuven BelgiumDivision of Gynecologic Oncology, Department of Obstetrics and Gynaecology and Leuven Cancer Institute University Hospitals Leuven Leuven BelgiumDivision of Gynecologic Oncology, Department of Obstetrics and Gynaecology and Leuven Cancer Institute University Hospitals Leuven Leuven BelgiumDepartment of Epidemiology, Director of Genetic Epidemiology Research Institute, Center for Cancer Genetics Research & Prevention, School of Medicine University of California Irvine Irvine CaliforniaDepartment of Epidemiology University of California Irvine Irvine CaliforniaCancer Research UK Cambridge Institute University of Cambridge Cambridge UKDepartment of Gynecology and Obstetrics Haukeland University Hospital Bergen NorwayDepartment of Gynecology and Obstetrics Haukeland University Hospital Bergen NorwayRadboud University Medical Center Radboud Institute for Health Sciences Nijmegen NetherlandsDepartment of Gynaecology, Radboud University Medical Center Radboud Institute for Molecular Life sciences Nijmegen The NetherlandsDepartment of Obstetrics & Gynecology Oregon Health & Science University Portland OregonDepartment of Obstetrics & Gynecology Oregon Health & Science University Portland OregonDepartment of Obstetrics & Gynecology Oregon Health & Science University Portland OregonDivision of Epidemiology and Biostatistics, Department of Internal Medicine University of New Mexico Albuquerque New MexicoCancer Control Research, British Columbia Cancer Agency Vancouver British Columbia CanadaCanada's Michael Smith Genome Sciences Centre British Columbia Cancer Agency Vancouver British Columbia CanadaHollings Cancer Center and Department of Public Health Sciences Medical University of South Carolina Charleston South CarolinaStrangeways Research laboratory, Department of Oncology, Department of Public Health and Primary Care University of Cambridge Cambridge UKStrangeways Research Laboratory, Department of Oncology University of Cambridge Cambridge UKCancer Genetics Laboratory, Research Division Peter MacCallum Cancer Centre Victoria AustraliaFaculty of Medicine University of Southampton Southampton UKCentre for Cancer Research The Westmead Institute for Medical Research, The University of Sydney Sydney New South Wales AustraliaCentre for Cancer Research The Westmead Institute for Medical Research, The University of Sydney Sydney New South Wales AustraliaDepartment of Public Health Sciences University of Virginia Charlottesville VirginiaAbstract An association between genetic variants in the vitamin D receptor (VDR) gene and epithelial ovarian cancer (EOC) was previously reported in women of African ancestry (AA). We sought to examine associations between genetic variants in VDR and additional genes from vitamin D biosynthesis and pathway targets (EGFR, UGT1A, UGT2A1/2, UGT2B, CYP3A4/5, CYP2R1, CYP27B1, CYP24A1, CYP11A1, and GC). Genotyping was performed using the custom‐designed 533,631 SNP Illumina OncoArray with imputation to the 1,000 Genomes Phase 3 v5 reference set in 755 EOC cases, including 537 high‐grade serous (HGSOC), and 1,235 controls. All subjects are of African ancestry (AA). Logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI). We further evaluated statistical significance of selected SNPs using the Bayesian False Discovery Probability (BFDP). A significant association with EOC was identified in the UGT2A1/2 region for the SNP rs10017134 (per allele OR = 1.4, 95% CI = 1.2‐1.7, P = 1.2 × 10−6, BFDP = 0.02); and an association with HGSOC was identified in the EGFR region for the SNP rs114972508 (per allele OR = 2.3, 95% CI = 1.6‐3.4, P = 1.6 × 10−5, BFDP = 0.29) and in the UGT2A1/2 region again for rs1017134 (per allele OR = 1.4, 95% CI = 1.2‐1.7, P = 2.3 × 10−5, BFDP = 0.23). Genetic variants in the EGFR and UGT2A1/2 may increase susceptibility of EOC in AA women. Future studies to validate these findings are warranted. Alterations in EGFR and UGT2A1/2 could perturb enzyme efficacy, proliferation in ovaries, impact and mark susceptibility to EOC.https://doi.org/10.1002/cam4.1996African ancestry riskgenetic associationovarian cancervitamin D pathway |
| spellingShingle | Delores J. Grant Ani Manichaikul Anthony J. Alberg Elisa V. Bandera Jill Barnholtz‐Sloan Melissa Bondy Michele L. Cote Ellen Funkhouser Patricia G. Moorman Lauren C. Peres Edward S. Peters Ann G. Schwartz Paul D. Terry Xin‐Qun Wang Temitope O. Keku Cathrine Hoyo Andrew Berchuck Dale P. Sandler Jack A. Taylor Katie M. O’Brien Digna R. Velez Edwards Todd L. Edwards Alicia Beeghly‐Fadiel Nicolas Wentzensen Celeste Leigh Pearce Anna H. Wu Alice S. Whittemore Valerie McGuire Weiva Sieh Joseph H. Rothstein Francesmary Modugno Roberta Ness Kirsten Moysich Mary Anne Rossing Jennifer A. Doherty Thomas A. Sellers Jennifer B. Permuth‐Way Alvaro N. Monteiro Douglas A. Levine Veronica Wendy Setiawan Christopher A. Haiman Loic LeMarchand Lynne R. Wilkens Beth Y. Karlan Usha Menon Susan Ramus Simon Gayther Aleksandra Gentry‐Maharaj Kathryn L. Terry Daniel W. Cramer Ellen L. Goode Melissa C. Larson Scott H. Kaufmann Rikki Cannioto Kunle Odunsi John L. Etter Ruea‐Yea Huang Marcus Q. Bernardini Alicia A. Tone Taymaa May Marc T. Goodman Pamela J. Thompson Michael E. Carney Shelley S. Tworoger Elizabeth M. Poole Diether Lambrechts Ignace Vergote Adriaan Vanderstichele Els Van Nieuwenhuysen Hoda Anton‐Culver Argyrios Ziogas James D. Brenton Line Bjorge Helga B. Salvensen Lambertus A. Kiemeney Leon F. A. G. Massuger Tanja Pejovic Amanda Bruegl Melissa Moffitt Linda Cook Nhu D. Le Angela Brooks‐Wilson Linda E. Kelemen Paul D.P. Pharoah Honglin Song Ian Campbell Diana Eccles Anna DeFazio Catherine J. Kennedy Joellen M. Schildkraut Evaluation of vitamin D biosynthesis and pathway target genes reveals UGT2A1/2 and EGFR polymorphisms associated with epithelial ovarian cancer in African American Women Cancer Medicine African ancestry risk genetic association ovarian cancer vitamin D pathway |
| title | Evaluation of vitamin D biosynthesis and pathway target genes reveals UGT2A1/2 and EGFR polymorphisms associated with epithelial ovarian cancer in African American Women |
| title_full | Evaluation of vitamin D biosynthesis and pathway target genes reveals UGT2A1/2 and EGFR polymorphisms associated with epithelial ovarian cancer in African American Women |
| title_fullStr | Evaluation of vitamin D biosynthesis and pathway target genes reveals UGT2A1/2 and EGFR polymorphisms associated with epithelial ovarian cancer in African American Women |
| title_full_unstemmed | Evaluation of vitamin D biosynthesis and pathway target genes reveals UGT2A1/2 and EGFR polymorphisms associated with epithelial ovarian cancer in African American Women |
| title_short | Evaluation of vitamin D biosynthesis and pathway target genes reveals UGT2A1/2 and EGFR polymorphisms associated with epithelial ovarian cancer in African American Women |
| title_sort | evaluation of vitamin d biosynthesis and pathway target genes reveals ugt2a1 2 and egfr polymorphisms associated with epithelial ovarian cancer in african american women |
| topic | African ancestry risk genetic association ovarian cancer vitamin D pathway |
| url | https://doi.org/10.1002/cam4.1996 |
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