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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.

Publication ,  Journal Article
Grant, DJ; Manichaikul, A; Alberg, AJ; Bandera, EV; Barnholtz-Sloan, J; Bondy, M; Cote, ML; Funkhouser, E; Moorman, PG; Peres, LC; Peters, ES ...
Published in: Cancer Med
May 2019

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.

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Published In

Cancer Med

DOI

EISSN

2045-7634

Publication Date

May 2019

Volume

8

Issue

5

Start / End Page

2503 / 2513

Location

United States

Related Subject Headings

  • Vitamin D
  • Receptors, Calcitriol
  • Polymorphism, Single Nucleotide
  • Ovarian Neoplasms
  • Neoplasm Grading
  • Middle Aged
  • Logistic Models
  • Humans
  • Glucuronosyltransferase
  • Genetic Association Studies
 

Citation

APA
Chicago
ICMJE
MLA
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Grant, D. J., Manichaikul, A., Alberg, A. J., Bandera, E. V., Barnholtz-Sloan, J., Bondy, M., … Schildkraut, J. 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 Med, 8(5), 2503–2513. https://doi.org/10.1002/cam4.1996
Grant, Delores J., Ani Manichaikul, Anthony J. Alberg, Elisa V. Bandera, Jill Barnholtz-Sloan, Melissa Bondy, Michele L. Cote, et al. “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 Med 8, no. 5 (May 2019): 2503–13. https://doi.org/10.1002/cam4.1996.
Grant DJ, Manichaikul A, Alberg AJ, Bandera EV, Barnholtz-Sloan J, Bondy M, et al. 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 Med. 2019 May;8(5):2503–13.
Grant, Delores J., et al. “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 Med, vol. 8, no. 5, May 2019, pp. 2503–13. Pubmed, doi:10.1002/cam4.1996.
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. 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 Med. 2019 May;8(5):2503–2513.
Journal cover image

Published In

Cancer Med

DOI

EISSN

2045-7634

Publication Date

May 2019

Volume

8

Issue

5

Start / End Page

2503 / 2513

Location

United States

Related Subject Headings

  • Vitamin D
  • Receptors, Calcitriol
  • Polymorphism, Single Nucleotide
  • Ovarian Neoplasms
  • Neoplasm Grading
  • Middle Aged
  • Logistic Models
  • Humans
  • Glucuronosyltransferase
  • Genetic Association Studies