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

Authors:
Delores J Grant
Delores J Grant
North Carolina Central University
United States
Ani Manichaikul
Ani Manichaikul
Center for Public Health Genomics
Charlottesville | United States
Anthony J Alberg
Anthony J Alberg
Medical University of South Carolina
United States
Elisa V Bandera
Elisa V Bandera
Rutgers Cancer Institute of New Jersey
New Brunswick | United States
Jill Barnholtz-Sloan
Jill Barnholtz-Sloan
Case Western Reserve University School of Medicine
United States
Melissa Bondy
Melissa Bondy
The University of Texas M. D. Anderson Cancer Center
Michele L Cote
Michele L Cote
Wayne State University School of Medicine
Ellen Funkhouser
Ellen Funkhouser
University of Alabama at Birmingham

Cancer Med 2019 Apr 18. Epub 2019 Apr 18.

Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia.

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 , 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 , 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 , 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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Source
https://onlinelibrary.wiley.com/doi/abs/10.1002/cam4.1996
Publisher Site
http://dx.doi.org/10.1002/cam4.1996DOI Listing
April 2019
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