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Evaluation of vitamin D biosynthesis and pathway target genes reveals UGT2A1/2 and EGFR polymorphisms associated with epithelial ovarian cancer in African American Women

dc.contributor.authorGrant, Delores J.
dc.contributor.authorManichaikul, Ani
dc.contributor.authorAlberg, Anthony J.
dc.contributor.authorBandera, Elisa V.
dc.contributor.authorBarnholtz‐sloan, Jill
dc.contributor.authorBondy, Melissa
dc.contributor.authorCote, Michele L.
dc.contributor.authorFunkhouser, Ellen
dc.contributor.authorMoorman, Patricia G.
dc.contributor.authorPeres, Lauren C.
dc.contributor.authorPeters, Edward S.
dc.contributor.authorSchwartz, Ann G.
dc.contributor.authorTerry, Paul D.
dc.contributor.authorWang, Xin‐qun
dc.contributor.authorKeku, Temitope O.
dc.contributor.authorHoyo, Cathrine
dc.contributor.authorBerchuck, Andrew
dc.contributor.authorSandler, Dale P.
dc.contributor.authorTaylor, Jack A.
dc.contributor.authorO’brien, Katie M.
dc.contributor.authorVelez Edwards, Digna R.
dc.contributor.authorEdwards, Todd L.
dc.contributor.authorBeeghly‐fadiel, Alicia
dc.contributor.authorWentzensen, Nicolas
dc.contributor.authorPearce, Celeste Leigh
dc.contributor.authorWu, Anna H.
dc.contributor.authorWhittemore, Alice S.
dc.contributor.authorMcGuire, Valerie
dc.contributor.authorSieh, Weiva
dc.contributor.authorRothstein, Joseph H.
dc.contributor.authorModugno, Francesmary
dc.contributor.authorNess, Roberta
dc.contributor.authorMoysich, Kirsten
dc.contributor.authorRossing, Mary Anne
dc.contributor.authorDoherty, Jennifer A.
dc.contributor.authorSellers, Thomas A.
dc.contributor.authorPermuth‐way, Jennifer B.
dc.contributor.authorMonteiro, Alvaro N.
dc.contributor.authorLevine, Douglas A.
dc.contributor.authorSetiawan, Veronica Wendy
dc.contributor.authorHaiman, Christopher A.
dc.contributor.authorLeMarchand, Loic
dc.contributor.authorWilkens, Lynne R.
dc.contributor.authorKarlan, Beth Y.
dc.contributor.authorMenon, Usha
dc.contributor.authorRamus, Susan
dc.contributor.authorGayther, Simon
dc.contributor.authorGentry‐maharaj, Aleksandra
dc.contributor.authorTerry, Kathryn L.
dc.contributor.authorCramer, Daniel W.
dc.contributor.authorGoode, Ellen L.
dc.contributor.authorLarson, Melissa C.
dc.contributor.authorKaufmann, Scott H.
dc.contributor.authorCannioto, Rikki
dc.contributor.authorOdunsi, Kunle
dc.contributor.authorEtter, John L.
dc.contributor.authorHuang, Ruea‐yea
dc.contributor.authorBernardini, Marcus Q.
dc.contributor.authorTone, Alicia A.
dc.contributor.authorMay, Taymaa
dc.contributor.authorGoodman, Marc T.
dc.contributor.authorThompson, Pamela J.
dc.contributor.authorCarney, Michael E.
dc.contributor.authorTworoger, Shelley S.
dc.contributor.authorPoole, Elizabeth M.
dc.contributor.authorLambrechts, Diether
dc.contributor.authorVergote, Ignace
dc.contributor.authorVanderstichele, Adriaan
dc.contributor.authorVan Nieuwenhuysen, Els
dc.contributor.authorAnton‐culver, Hoda
dc.contributor.authorZiogas, Argyrios
dc.contributor.authorBrenton, James D.
dc.contributor.authorBjorge, Line
dc.contributor.authorSalvensen, Helga B.
dc.contributor.authorKiemeney, Lambertus A.
dc.contributor.authorMassuger, Leon F. A. G.
dc.contributor.authorPejovic, Tanja
dc.contributor.authorBruegl, Amanda
dc.contributor.authorMoffitt, Melissa
dc.contributor.authorCook, Linda
dc.contributor.authorLe, Nhu D.
dc.contributor.authorBrooks‐wilson, Angela
dc.contributor.authorKelemen, Linda E.
dc.contributor.authorPharoah, Paul D.P.
dc.contributor.authorSong, Honglin
dc.contributor.authorCampbell, Ian
dc.contributor.authorEccles, Diana
dc.contributor.authorDeFazio, Anna
dc.contributor.authorKennedy, Catherine J.
dc.contributor.authorSchildkraut, Joellen M.
dc.date.accessioned2019-06-20T17:05:13Z
dc.date.available2020-07-01T17:47:46Zen
dc.date.issued2019-05
dc.identifier.citationGrant, Delores J.; Manichaikul, Ani; Alberg, Anthony J.; Bandera, Elisa V.; Barnholtz‐sloan, Jill ; Bondy, Melissa; Cote, Michele L.; Funkhouser, Ellen; Moorman, Patricia G.; Peres, Lauren C.; Peters, Edward S.; Schwartz, Ann G.; Terry, Paul D.; Wang, Xin‐qun ; Keku, Temitope O.; Hoyo, Cathrine; Berchuck, Andrew; Sandler, Dale P.; Taylor, Jack A.; O’brien, Katie M. ; Velez Edwards, Digna R.; Edwards, Todd L.; Beeghly‐fadiel, Alicia ; Wentzensen, Nicolas; Pearce, Celeste Leigh; Wu, Anna H.; Whittemore, Alice S.; McGuire, Valerie; Sieh, Weiva; Rothstein, Joseph H.; Modugno, Francesmary; Ness, Roberta; Moysich, Kirsten; Rossing, Mary Anne; Doherty, Jennifer A.; Sellers, Thomas A.; Permuth‐way, Jennifer B. ; Monteiro, Alvaro N.; Levine, Douglas A.; Setiawan, Veronica Wendy; Haiman, Christopher A.; LeMarchand, Loic; Wilkens, Lynne R.; Karlan, Beth Y.; Menon, Usha; Ramus, Susan; Gayther, Simon; Gentry‐maharaj, Aleksandra ; Terry, Kathryn L.; Cramer, Daniel W.; Goode, Ellen L.; Larson, Melissa C.; Kaufmann, Scott H.; Cannioto, Rikki; Odunsi, Kunle; Etter, John L.; Huang, Ruea‐yea ; Bernardini, Marcus Q.; Tone, Alicia A.; May, Taymaa; Goodman, Marc T.; Thompson, Pamela J.; Carney, Michael E.; Tworoger, Shelley S.; Poole, Elizabeth M.; Lambrechts, Diether; Vergote, Ignace; Vanderstichele, Adriaan; Van Nieuwenhuysen, Els; Anton‐culver, Hoda ; Ziogas, Argyrios; Brenton, James D.; Bjorge, Line; Salvensen, Helga B.; Kiemeney, Lambertus A.; Massuger, Leon F. A. G.; Pejovic, Tanja; Bruegl, Amanda; Moffitt, Melissa; Cook, Linda; Le, Nhu D.; Brooks‐wilson, Angela ; Kelemen, Linda E.; Pharoah, Paul D.P.; Song, Honglin; Campbell, Ian; Eccles, Diana; DeFazio, Anna; Kennedy, Catherine J.; Schildkraut, Joellen M. (2019). "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 8(5): 2503-2513.
dc.identifier.issn2045-7634
dc.identifier.issn2045-7634
dc.identifier.urihttps://hdl.handle.net/2027.42/149527
dc.description.abstractAn 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 customâ designed 533,631 SNP Illumina OncoArray with imputation to the 1,000 Genomes Phase 3 v5 reference set in 755 EOC cases, including 537 highâ 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 = 1.2â 1.7, P = 1.2 à  10â 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 = 1.6â 3.4, P = 1.6 à  10â 5, BFDP = 0.29) and in the UGT2A1/2 region again for rs1017134 (per allele OR = 1.4, 95% CI = 1.2â 1.7, P = 2.3 à  10â 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.We sought to examine associations 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). A significant association with EOC was identified in the UGT2A1/2 region for the SNP rs10017134 (per allele OR = 1.4, 95% CI = 1.2â 1.7, P = 1.2 à  10â 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 = 1.6â 3.4, P = 1.6 à  10â 5, BFDP = 0.29) and in the UGT2A1/2 region again for rs1017134 (per allele OR = 1.4, 95% CI = 1.2â 1.7, P = 2.3 à  10â 5, BFDP = 0.23). Alterations in EGFR and UGT2A1/2 could perturb enzyme efficacy, proliferation in ovaries, impact and mark susceptibility to EOC.
dc.publisherWiley Periodicals, Inc.
dc.subject.othervitamin D pathway
dc.subject.otherAfrican ancestry risk
dc.subject.othergenetic association
dc.subject.otherovarian cancer
dc.titleEvaluation of vitamin D biosynthesis and pathway target genes reveals UGT2A1/2 and EGFR polymorphisms associated with epithelial ovarian cancer in African American Women
dc.typeArticle
dc.rights.robotsIndexNoFollow
dc.subject.hlbsecondlevelHematology and Oncology
dc.subject.hlbtoplevelHealth Sciences
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/149527/1/cam41996_am.pdf
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/149527/2/cam41996.pdf
dc.identifier.doi10.1002/cam4.1996
dc.identifier.sourceCancer Medicine
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dc.owningcollnameInterdisciplinary and Peer-Reviewed


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