Citations 22
Evaluation of vitamin D biosynthesis and pathway target genes reveals UGT2A1/2 and EGFR polymorphisms associated with epithelial ovarian cancer in African American Women
Grant, Delores J. , Alberg, Anthony J. , Barnholtz‐Sloan, Jill S. , Bondy, Melissa L. , Funkhouser, Ellen, Moorman, Patricia G. , Peres, Lauren C. , Peters, Edward , Schwartz, Ann G. , Terry, Paul , Wang, Xin‐Qun, Hoyo, Cathrine , Sandler, Dale P. , Taylor, Jack A. , Edwards, Todd L., Beeghly‐Fadiel, Alicia, Wentzensen, Nicolas , Pearce, Celeste Leigh , Wu, Anna H. , Whittemore, Alice S. , McGuire, Valerie , Sieh, Weiva , Rothstein, Joseph H. , Ness, Roberta B., Moysich, Kirsten B. , Rossing, Mary Anne, Sellers, Thomas A. , Monteiro, Álvaro N.A. , Levine, Douglas A. , Haiman, Christopher A. , Menon, Usha , Ramus, Susan J. , Gayther, Simon A. , Terry, Kathryn L. , Goode, Ellen L. , Cannioto, Rikki , Odunsi, Kunle , Etter, John Lewis , Huang, Ruea‐Yea , Bernardini, Marcus Q. , Tone, Alicia , May, Taymaa, Goodman, Marc T. , Thompson, Pamela J., Carney, Michael E. , Tworoger, Shelley S. , Lambrechts, Diether , Vergote, Ignace , Nieuwenhuysen, Els Van , Salvensen, Helga B., Massuger, Leon F.A.G. , Bruegl, Amanda , Moffitt, Melissa , Le, Nhu D. , Brooks‐Wilson, Angela , Kelemen, Linda E. , Song, Honglin , Eccles, Diana , DeFazio, Anna , Kennedy, Catherine J. , Schildkraut, Joellen M. , Lambrechts, Diether , Barnholtz-Sloan, Jill S , Moysich, Kirsten , Permuth, Jennifer B , Cramer, Daniel W , Fazio, Anna de , Lambrechts, Diether , Ramus, Susan J , Sandler, Dale P , Tworoger, Shelley S , Eccles, Diana , Menon, Usha , Monteiro, Alvaro N , Brooks-Wilson, Angela R , Kennedy, Catherine J , Lambrechts, Diether , Sieh, Weiva , Taylor, Jack A , Goodman, Marc T , Manichaikul, Ani , Bandera, Elisa V. , Coté, Michele L. , Keku, Temitope O , Berchuck, Andrew , O’Brien, Katie M. , Edwards, Digna R. Velez , Beeghly‐Fadiel, Alicia , Modugno, Francesmary , Doherty, Jennifer A. , Permuth, Jennifer B. , Setiawan, Veronica Wendy , Marchand, Loı̈c Le , Wilkens, Lynne R. , Karlan, Beth Y. , Gentry‐Maharaj, Aleksandra , Cramer, Daniel W. , Larson, Melissa C. , Kaufmann, Scott H. , Poole, Elizabeth M. , Vanderstichele, Adriaan , Anton‐Culver, Hoda , Ziogas, Argyrios , Brenton, James D. , Bjørge, Line , Kiemeney, Lambertus A. , Pejovic, Tanja B. , Cook, Linda S. , Pharoah, Paul D.P. , Campbell, Ian
Cancer Medicine | April 19, 2019 | Volume: 8 | Issue: 5 | Pages: 2503-2513
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.
The OncoArray Consortium: A Network for Understanding the Genetic Architecture of Common Cancers
Wang, Zhaoming , Schumacher, Fredrick R. , Gayther, Simon A. , Casey, Graham , Sellers, Thomas A. , Gruber, Stephen B., Dunning, Alison M. , Michailidou, Kyriaki , Fachal, Laura , Doheny, Kimberly F. , Li, Yafang , Xiao, Xiangjun , Romm, Jane, Pugh, Elizabeth, Coetzee, Gerhard A. , Hazelett, Dennis J. , Bojesen, Stig E. , Caga-Anan, Charlisse , Haiman, Christopher A. , Kamal, Ahsan , Luccarini, Craig , Tessier, Daniel C., Vincent, Daniel , Bacot, François, Berg, David Van Den , Nelson, Stefanie A. , Demetriades, Stephen, Goldgar, David E., Forman, Judith L., Conti, David V. , Bickeböller, Heike , Risch, Angela , Waldenberger, Mélanie , Brüske‐Hohlfeld, Irene, Hicks, Belynda , McGuffog, Lesley, Kuchenbaecker, Karoline , Soucy, Penny, Manz, Judith, Cunningham, Julie M. , Butterbach, Katja, Kote‐Jarai, Zsofia , Kraft, Peter , Lindström, Sara , Adams, Marcia, McKay, James , Phelan, Catherine M., Benlloch, Sara, Kelemen, Linda E., Brennan, Paul , Riggan, Marjorie J. , O’Mara, Tracy A. , Shen, Hongbing , Shi, Yongyong , Thompson, Deborah J. , Goodman, Marc T. , Nielsen, Sune F. , LaBoissière, Sylvie, Schmit, Stephanie L. , Shelford, Tameka, Edlund, Christopher K., Taylor, Jack A. , Field, John K. , Park, Sue K. , Offit, Kenneth , Thomassen, Mads , Schmutzler, Rita K., Ottini, Laura , Hung, Rayjean J., Olama, Ali Amin Al , Peters, Ulrike , Eeles, Rosalind A. , Seldin, Michael F., Gillanders, Elizabeth M. , Seminara, Daniela, Antoniou, Antonis C. , Chenevix‐Trench, Georgia , Simard, Jacques , Easton, Douglas F. , Durocher, Francine , Hung, Rayjean J. , Amos, Christopher I. , Dennis, Joe , Byun, Jinyoung , Hunter, David J. , Spurdle, Amanda B. , Couch, Fergus J. , Giles, Graham G. , Ling, Hua , Lee, Andrew , FitzGerald, Liesel M. , Berchuck, Andrew , Marchini, Jonathan , Pharoah, Paul D.P. , Chanock, Stephen Jacob , Hazelett, Dennis J , Eeles, Rosalind A , Van Den Berg, David J , Hung, Rayjean J , Wang, Zhaoming , O'Mara, Tracy A , Field, John K , Dunning, Alison M , Michailidou, Kyriaki , Taylor, Jack A , Kraft, Peter , Simard, Jacques , Chenevix-Trench, Georgia , Ottini, Laura , Conti, David V , Bojesen, Stig E , Risch, Angela , Bickeböller, Heike , Shen, Hongbing , Goodman, Marc T , Fachal, Laura
Cancer Epidemiology, Biomarkers & Prevention | October 3, 2016 | Volume: 26 | Issue: 1 | Pages: 126-135
Abstract Background: Common cancers develop through a multistep process often including inherited susceptibility. Collaboration among multiple institutions, and funding from multiple sources, has allowed the development of an inexpensive genotyping microarray, the OncoArray. The array includes a genome-wide backbone, comprising 230,000 SNPs tagging most common genetic variants, together with dense mapping of known susceptibility regions, rare variants from sequencing experiments, pharmacogenetic markers, and cancer-related traits. Methods: The OncoArray can be genotyped using a novel technology developed by Illumina to facilitate efficient genotyping. The consortium developed standard approaches for selecting SNPs for study, for quality control of markers, and for ancestry analysis. The array was genotyped at selected sites and with prespecified replicate samples to permit evaluation of genotyping accuracy among centers and by ethnic background. Results: The OncoArray consortium genotyped 447,705 samples. A total of 494,763 SNPs passed quality control steps with a sample success rate of 97% of the samples. Participating sites performed ancestry analysis using a common set of markers and a scoring algorithm based on principal components analysis. Conclusions: Results from these analyses will enable researchers to identify new susceptibility loci, perform fine-mapping of new or known loci associated with either single or multiple cancers, assess the degree of overlap in cancer causation and pleiotropic effects of loci that have been identified for disease-specific risk, and jointly model genetic, environmental, and lifestyle-related exposures. Impact: Ongoing analyses will shed light on etiology and risk assessment for many types of cancer. Cancer Epidemiol Biomarkers Prev; 26(1); 126–35. ©2016 AACR.