Citations 2
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.
Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types
Kar, Siddhartha , Beesley, Jonathan, Olama, Ali Amin Al , Michailidou, Kyriaki , Lawrenson, Kate , Lindström, Sara, Ramus, Susan J. , Thompson, Deborah J. , Investigators, ABCTB, Kibel, Adam S. , Dansonka‐Mieszkowska, Agnieszka , Michael, Agnieszka , Dieffenbach, Aida Karina, Whittemore, Alice S. , Monteiro, Álvaro N.A. , Peixoto, Ana , González‐Neira, Anna , Wu, Anna H. , Lindblom, Annika , Swerdlow, Anthony J. , Cancer), AOCS Study Group & Australian Cancer Study (Ovarian, BioResource, APCB, Ekici, Arif B. , Burwinkel, Barbara , Nordestgaard, Børge G. , Blomqvist, Carl , Phelan, Catherine, McLean, Catriona , Pearce, Celeste Leigh, Vachon, Celine M. , Stegmaier, Christa, Maier, Christiane, Høgdall, Claus , Kang, Daehee , Tessier, Daniel C., Schaid, Daniel J. , Neal, David E. , Eccles, Diana , Flesch‐Janys, Dieter, Wokozorczyk, Dominika, Levine, Douglas A. , Yannoukakos, Drakoulis , Sawyer, Elinor J. , Goode, Ellen L. , Хуснутдинова, Э. К. , Høgdall, Estrid , Song, Fengju, Bruinsma, Fiona, Heitz, Florian , Hamdy, Freddie C. , Olsson, Håkan , Wildiers, Hans , Ulmer, Hans-Ulrich, Pandha, Hardev , Darabi, Hatef, Salvesen, Helga B., Grönberg, Henrik , Brenner, Hermann , Brauch, Hiltrud , Song, Honglin , Lim, Hui-Yi, McNeish, Iain A. , Campbell, Ian , Vergote, Ignace , Lubiński, Jan , Stanford, Janet L. , Benı́tez, Javier , Chang‐Claude, Jenny , Donovan, Jenny , Schildkraut, Joellen M. , Schleutker, Johanna , Hopper, John L. , Kupryjańczyk, Jolanta , Figueroa, Jonine D. , Clements, Judith A. , Knight, Julia A. , Peto, Julian , Cunningham, Julie M. , Pow‐Sang, Julio M. , Batra, Jyotsna , Lu, Karen H., Herkommer, Kathleen , Investigators, kConFab, Matsuo, Keitaro , Muir, Kenneth , Offitt, Kenneth, Chen, Kexin , Moysich, Kirsten B., Aittomäki, Kristiina, Odunsi, Kunle , Kiemeney, Lambertus A. , Massuger, Leon F.A.G. , Hooning, Maartje J. , Pike, Malcolm C., Bolla, Manjeet K. , Luedeke, Manuel, Teixeira, Manuel R. , Goodman, Marc T. , Schmidt, Marjanka K. , Riggan, Marjorie J. , Rossing, Mary Anne, Beckmann, Matthias W. , Moisse, Matthieu , Southey, Melissa C. , Jones, Michael E. , Hildebrandt, Michelle A.T., Hou, Ming‐Feng , Schoemaker, Minouk J. , García‐Closas, Montserrat , Bogdanova, Natalia , Investigators, NBCS, Le, Nhu D. , Orr, Nick , Wentzensen, Nicolas , Pashayan, Nora , Peterlongo, Paolo , Guénel, Pascal , Brennan, Paul , Paulo, Paula , Webb, Penelope M. , Broberg, Per, Fasching, Peter A. , Devilee, Peter , Wang, Qin, Kaneva, Radka , Kopperud, Reidun Kristin, Schmutzler, Rita K., Stephenson, Robert A., MacInnis, Robert J. , Hoover, Robert N. , Winqvist, Robert , Ness, Roberta B., Travis, Ruth C. , Benlloch, Sara, Olson, Sara H. , McDonnell, Shannon K. , Tworoger, Shelley S. , Maia, Sofia , Berndt, Sonja I., Lee, Soo Chin , Teo, Soo‐Hwang , Thibodeau, Stephen N. , Bojesen, Stig E. , Gapstur, Susan M. , Tammela, Teuvo L.J. , Network, the GENICA, Dörk, Thilo , Brüning, Thomas , Wahlfors, Tiina , Edwards, Todd L., Menon, Usha , Hamann, Ute , Mitev, Vanio , Kosma, Veli‐Matti , Setiawan, Veronica Wendy , Kristensen, Vessela, Vogel, Walther , Zheng, Wei , Sieh, Weiva , Blot, William J. , Kluźniak, Wojciech , Gao, Yu‐Tang , Schumacher, Fredrick R. , Freedman, Matthew L., Dunning, Alison M. , Simard, Jacques , Haiman, Christopher A. , Sellers, Thomas A. , Hunter, David J. , Henderson, Brian E., Kraft, Peter , Gayther, Simon A. , Easton, Douglas F. , Chenevix‐Trench, Georgia , Eeles, Rosalind A. , Lambrechts, Diether , Lu, Karen H. , Durocher, Francine , Zheng, Wei , Thorne, Heather , Lambrechts, Diether , Chen, Kexin , Vachon, Celine, Tyrer, Jonathan P. , Kote‐Jarai, Zsofia , Investigators, ABCTB, Gentry‐Maharaj, Aleksandra , Wolk, Alicja , Kierzek, Andrzej , Cox, Angela , Rudolph, Anja , Cancer), AOCS Study Group & Australian Cancer Study (Ovarian, BioResource, APCB, Ziogas, Argyrios , Karlan, Beth Y. , Vachon, Celine M. , Cybulski, Cezary , Slavov, Chavdar , Ambrosone, Christine B. , Teerlink, Craig C. , Stram, Daniel O. , Cramer, Daniel W. , Edwards, Digna R. Velez , Bandera, Elisa V. , Poole, Elizabeth M. , Song, Fengju , Modugno, Francesmary , Wiklund, Fredrik E. , Giles, Graham G. , Risch, Harvey A. , Nevanlinna, Heli , Anton‐Culver, Hoda , Gronwald, Jacek , Doherty, Jennifer A. , Permuth, Jennifer B. , Dennis, Joe , Park, Jong Y. , Czene, Kamila , Khaw, Kay‐Tee , Investigators, kConFab, Moysich, Kirsten B., FitzGerald, Liesel M. , Cook, Linda S. , Cannon‐Albright, Lisa , Hooning, Maartje J. , Aly, Markus , Sanderson, Maureen , Lush, Michael J. , Hildebrandt, Michelle A.T. , Rahman, Nazneen , Investigators, NBCS, Wang, Qin, Cai, Qiuyin , Li, Qiyuan , Bützow, Ralf C. , Milne, Roger L. , Berndt, Sonja I. , Kjær, Susanne K. , Pejovic, Tanja B. , Network, the GENICA, Key, Tim , Kristensen, Vessela N. , Arndt, Volker , Shu, Xiao‐Ou , Berchuck, Andrew , Spurdle, Amanda B. , Chanock, Stephen Jacob , Couch, Fergus J. , Hall, Per N , Pharoah, Paul D.P. , Dörk, Thilo , Lambrechts, Diether , Kiemeney, Lambertus A , McNeish, Iain A , Peterlongo, Paolo , Ramus, Susan J , Teixeira, Manuel R , Teo, Soo H , Tworoger, Shelley S , Webb, Penelope M , Eccles, Diana , Menon, Usha , Lawrenson, Kate , Monteiro, Alvaro N , Swerdlow, Anthony J , Moysich, Kirsten , Campbell, Ian G , Eeles, Rosalind A , Southey, Melissa C , Donovan, Jenny L , Muir, Kenneth , Schleutker, Johanna , Travis, Ruth C , Pashayan, Nora , Michael, Agnieszka , Maclnnis, Robert , Matsuo, Keitaro , Dunning, Alison M , Heitz, Florian , Jones, Michael E , Kupryjanczyk, Jolanta , Lambrechts, Diether , Sieh, Weiva , Brenner, Hermann , Guénel, Pascal , García-Closas, Montserrat , Schmidt, Marjanka K , Ekici, Arif B , Moisse, Matthieu , Michailidou, Kyriaki , Bogdanova, Natalia V , Kraft, Peter , Benitez, Javier , Simard, Jacques , Chenevix-Trench, Georgia , Zheng, Wei , Figueroa, Jonine D , Høgdall, Estrid , Høgdall, Claus K , Kar, Siddhartha , Batra, Jyotsna , Clements, Judith , Setiawan, Veronica W , Yannoukakos, Drakoulis , Devilee, Peter , Lubinski, Jan , Bojesen, Stig E , Schoemaker, Minouk J , Goodman, Marc T , Wildiers, Hans , Mclean, Catriona , Brauch, Hiltrud , Lindblom, Annika , Sawyer, Elinor J , Orr, Nick , McDonnell, Shannon K , Kang, Daehee
Cancer Discovery | July 18, 2016 | Volume: 6 | Issue: 9 | Pages: 1052-1067
Abstract Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10−8 seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type–specific expression quantitative trait locus and enhancer–gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10−5 in the three-cancer meta-analysis. Significance: We demonstrate that combining large-scale GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers. Cancer Discov; 6(9); 1052–67. ©2016 AACR. This article is highlighted in the In This Issue feature, p. 932