eprintid: 10072660
rev_number: 20
eprint_status: archive
userid: 608
dir: disk0/10/07/26/60
datestamp: 2019-04-29 16:51:46
lastmod: 2021-12-13 03:19:02
status_changed: 2019-04-29 16:51:46
type: article
metadata_visibility: show
creators_name: Grant, DJ
creators_name: Manichaikul, A
creators_name: Alberg, AJ
creators_name: Bandera, EV
creators_name: Barnholtz-Sloan, J
creators_name: Bondy, M
creators_name: Cote, ML
creators_name: Funkhouser, E
creators_name: Moorman, PG
creators_name: Peres, LC
creators_name: Peters, ES
creators_name: Schwartz, AG
creators_name: Terry, PD
creators_name: Wang, X-Q
creators_name: Keku, TO
creators_name: Hoyo, C
creators_name: Berchuck, A
creators_name: Sandler, DP
creators_name: Taylor, JA
creators_name: O'Brien, KM
creators_name: Velez Edwards, DR
creators_name: Edwards, TL
creators_name: Beeghly-Fadiel, A
creators_name: Wentzensen, N
creators_name: Pearce, CL
creators_name: Wu, AH
creators_name: Whittemore, AS
creators_name: McGuire, V
creators_name: Sieh, W
creators_name: Rothstein, JH
creators_name: Modugno, F
creators_name: Ness, R
creators_name: Moysich, K
creators_name: Rossing, MA
creators_name: Doherty, JA
creators_name: Sellers, TA
creators_name: Permuth-Way, JB
creators_name: Monteiro, AN
creators_name: Levine, DA
creators_name: Setiawan, VW
creators_name: Haiman, CA
creators_name: LeMarchand, L
creators_name: Wilkens, LR
creators_name: Karlan, BY
creators_name: Menon, U
creators_name: Ramus, S
creators_name: Gayther, S
creators_name: Gentry-Maharaj, A
creators_name: Terry, KL
creators_name: Cramer, DW
creators_name: Goode, EL
creators_name: Larson, MC
creators_name: Kaufmann, SH
creators_name: Cannioto, R
creators_name: Odunsi, K
creators_name: Etter, JL
creators_name: Huang, R-Y
creators_name: Bernardini, MQ
creators_name: Tone, AA
creators_name: May, T
creators_name: Goodman, MT
creators_name: Thompson, PJ
creators_name: Carney, ME
creators_name: Tworoger, SS
creators_name: Poole, EM
creators_name: Lambrechts, D
creators_name: Vergote, I
creators_name: Vanderstichele, A
creators_name: Van Nieuwenhuysen, E
creators_name: Anton-Culver, H
creators_name: Ziogas, A
creators_name: Brenton, JD
creators_name: Bjorge, L
creators_name: Salvensen, HB
creators_name: Kiemeney, LA
creators_name: Massuger, LFAG
creators_name: Pejovic, T
creators_name: Bruegl, A
creators_name: Moffitt, M
creators_name: Cook, L
creators_name: Le, ND
creators_name: Brooks-Wilson, A
creators_name: Kelemen, LE
creators_name: Pharoah, PDP
creators_name: Song, H
creators_name: Campbell, I
creators_name: Eccles, D
creators_name: DeFazio, A
creators_name: Kennedy, CJ
creators_name: Schildkraut, JM
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
ispublished: inpress
divisions: UCL
divisions: B02
divisions: D65
divisions: J38
keywords: African ancestry risk, genetic association, ovarian cancer, vitamin D pathway
note: Copyright © 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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.
date: 2019-04-18
date_type: published
official_url: http://doi.org/10.1002/cam4.1996
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1649389
doi: 10.1002/cam4.1996
lyricists_name: Gentry-Maharaj, Aleksandra
lyricists_name: Menon, Usha
lyricists_id: AGENT07
lyricists_id: UMENO29
actors_name: Bracey, Alan
actors_id: ABBRA90
actors_role: owner
full_text_status: public
publication: Cancer Medicine
event_location: United States
issn: 2045-7634
citation:        Grant, DJ;    Manichaikul, A;    Alberg, AJ;    Bandera, EV;    Barnholtz-Sloan, J;    Bondy, M;    Cote, ML;                                                                                                                                                                                                                                                                                                                                             ... Schildkraut, JM; + view all <#>        Grant, DJ;  Manichaikul, A;  Alberg, AJ;  Bandera, EV;  Barnholtz-Sloan, J;  Bondy, M;  Cote, ML;  Funkhouser, E;  Moorman, PG;  Peres, LC;  Peters, ES;  Schwartz, AG;  Terry, PD;  Wang, X-Q;  Keku, TO;  Hoyo, C;  Berchuck, A;  Sandler, DP;  Taylor, JA;  O'Brien, KM;  Velez Edwards, DR;  Edwards, TL;  Beeghly-Fadiel, A;  Wentzensen, N;  Pearce, CL;  Wu, AH;  Whittemore, AS;  McGuire, V;  Sieh, W;  Rothstein, JH;  Modugno, F;  Ness, R;  Moysich, K;  Rossing, MA;  Doherty, JA;  Sellers, TA;  Permuth-Way, JB;  Monteiro, AN;  Levine, DA;  Setiawan, VW;  Haiman, CA;  LeMarchand, L;  Wilkens, LR;  Karlan, BY;  Menon, U;  Ramus, S;  Gayther, S;  Gentry-Maharaj, A;  Terry, KL;  Cramer, DW;  Goode, EL;  Larson, MC;  Kaufmann, SH;  Cannioto, R;  Odunsi, K;  Etter, JL;  Huang, R-Y;  Bernardini, MQ;  Tone, AA;  May, T;  Goodman, MT;  Thompson, PJ;  Carney, ME;  Tworoger, SS;  Poole, EM;  Lambrechts, D;  Vergote, I;  Vanderstichele, A;  Van Nieuwenhuysen, E;  Anton-Culver, H;  Ziogas, A;  Brenton, JD;  Bjorge, L;  Salvensen, HB;  Kiemeney, LA;  Massuger, LFAG;  Pejovic, T;  Bruegl, A;  Moffitt, M;  Cook, L;  Le, ND;  Brooks-Wilson, A;  Kelemen, LE;  Pharoah, PDP;  Song, H;  Campbell, I;  Eccles, D;  DeFazio, A;  Kennedy, CJ;  Schildkraut, JM;   - view fewer <#>    (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        10.1002/cam4.1996 <https://doi.org/10.1002/cam4.1996>.    (In press).    Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10072660/1/Grant_et_al-2019-Cancer_Medicine.pdf