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: Grant 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. 
Published: April 2019

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 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.