Citations 35
Association of Genomic Domains in BRCA1 and BRCA2 with Prostate Cancer Risk and Aggressiveness
Patel, Vivek , Busch, Evan L. , Cronin, Angel M., Leslie, Goska , McGuffog, Lesley, Adlard, Julian , Agata, Simona , Agnarsson, Bjarni A. , Ahmed, Munaza, Aittomäki, Kristiina, Alducci, Elisa, Andrulis, Irene L. , Arason, Aðalgeir , Artioli, Grazia, Arver, Brita, Auber, Bernd , Azzollini, Jacopo , Barkardóttir, Rósa B. , Barroso, Alicia, Barrowdale, Daniel , Belotti, Muriel, Bertelsen, Birgitte , Blok, Marinus J. , Bodrogi, I., Bonadona, Valérie, Bondavalli, Davide , Boonen, Susanne E. , Borde, Julika , Borg, Åke , Bradbury, Angela R. , Brady, Angela, Brewer, Carole, Brunet, Joan , Buecher, Bruno , Caldés, Trinidad , Caliebe, Almuth , Calvello, Mariarosaria , Carrasco, Estela , Chan, Tsun Leung , Claes, Kathleen , Collaborators, GEMO Study, Collaborators, EMBRACE, Cortesi, Laura , Daly, Mary B., Damante, Giuseppe , Darder, Esther , Davidson, Rosemarie, Puppa, Lara Della , Ding, Yuan Chun , Ditsch, Nina , Donaldson, Alan, Dworniczak, Bernd , Easton, Douglas F. , Eccles, Diana M., Eeles, Rosalind A. , Ehrencrona, Hans , Ejlertsen, Bent , Engel, Christoph , Evans, D. Gareth , Faivre, Laurence, Faust, Ulrike , Feliubadaló, Lídia , Foretová, Lenka , Fountzilas, George , Frost, Debra, García‐Barberán, Vanesa , Gauthier‐Villars, Marion , Géczi, Lajos , Gehrig, Andrea, Gesta, Paul , Giannini, Giuseppe , Glendon, Gord , Goldgar, David E. , Greene, Mark H. , Gutierrez‐Barrera, Angelica M. , Hahnen, Eric , Hamann, Ute, Hauke, Jan , Herold, Natalie, Hogervorst, Frans B.L., Honisch, Ellen, Hulick, Peter J. , Investigators, kConFab, Investigators, Hebon, Izatt, Louise , Jager, Agnes , James, Paul A. , Janavičius, Ramūnas , Jensen, Uffe Birk , Jensen, Thomas D., Johannsson, Oskar T., John, Esther M. , Kang, Eunyoung , Kast, Karin, Kiiski, Johanna I. , Kim, Sung-Won, Ko, Kwang‐Pil , Konstantopoulou, Irene , Kramer, Gero , Krogh, Lotte, Kruse, Torben A., Kwong, Ava , Larsen, Mirjam, Lasset, Christine , Lautrup, Charlotte Kvist , Lee, Jihyoun , Lee, Jong Won, Lee, Min Hyuk , Lesueur, Fabienne , Liljegren, Annelie , Lindblom, Annika , Llovet, Patricia , López‐Fernández, Adrià , López‐Perolio, Irene, Lorca, Víctor , Loud, Jennifer T. , S.K., Edmond , Mai, Phuong L., Manoukian, Siranoush , Mari, Véronique , Martin, Lynn , Matricardi, Laura , Mebirouk, Noura, Medici, Veronica, Meijers‐Heijboer, Hanne , Meindl, Alfons , Mensenkamp, Arjen R. , Miller, Clare , Gomes, D. Molina , Montagna, Marco , Mooij, Thea M. , Mouret‐Fourme, Emmanuelle, Nathanson, Katherine L. , Navrátilová, Marie , Niederacher, Dieter , Nielsen, Finn C., Ņikitina-Zaķe, Liene , Offit, Kenneth, Oláh, Edith , Olopade, Olufunmilayo I. , Ong, Kai-Ren, Osório, Ana , Ott, Claus‐Eric , Park, Sue K. , Pedersen, Inge Søkilde , Peissel, Bernard , Peixoto, Ana , Peterlongo, Paolo , Petersen, Annabeth Høgh , Porteous, Mary, Pujana, Miguel Ángel , Ramser, Juliane, Rantala, Johanna, Rashid, Muhammad Usman , Rhiem, Kerstin, Rizzolo, Piera , Rookus, Matti A. , Rossing, Caroline Maria, Ruddy, Kathryn J. , Santos, Catarina , Saule, Claire , Scarpitta, Rosa , Schmutzler, Rita K., Schuster, Hélène, Senter, Leigha , Seynaeve, Caroline, Shah, Payal D. , Silvestri, Valentina , Simard, Jacques , Skytte, Anne‐Bine , Snape, Katie , Solano, Ángela R. , Soucy, Penny, Sunde, Lone , Sutter, Christian , Tan, Yen Y. , Teixeira, Manuel R. , Teo, Soo‐Hwang , Thomassen, Mads , Tibiletti, Maria Grazia , Toland, Amanda Ewart, Torres, Diana , Trainer, Alison H., Baan, Frederieke H. van der , Kolk, Lizet E. van der, Hest, Liselotte P. van , Varesco, Liliana , Varon-Mateeva, Raymonda, Viel, Alessandra , Vierstraete, Jeroen , Villa, Roberta, Wachenfeldt, Anna von , Wagner, Philipp , Wang‐Gohrke, Shan , Wappenschmidt, Barbara , Weitzel, Jeffrey N. , Wieme, Greet , Yadav, Siddhartha , Yoon, Sook‐Yee , Zanzottera, Cristina , Zorn, Kristin K. , D’Amico, Anthony V. , Freedman, Matthew L. , Pomerantz, Mark M., Chenevix‐Trench, Georgia , Antoniou, Antonis C. , Ottini, Laura , Nielsen, Henriette Roed, Durocher, Francine , Eccles, Diana , Caputo, Sandrine M. , Faivre, Laurence , Leslie, Goska , Adlard, Julian , Arnold, Norbert , Auber, Bernd , Azzollini, Jacopo , Barnes, Daniel R , Brunet, Joan , Caligo, Maria A , Campbell, Ian G , Claes, Kathleen B M , Darder, Esther , Dennis, Joe , Dworniczak, Bernd , Eeles, Rosalind A , Ehrencrona, Hans , Ejlertsen, Bent , Evans, D Gareth , Garre, Pilar , Greene, Mark H , Hulick, Peter J , Jager, Agnes , James, Paul , John, Esther M , Joseph, Vijai , Kim, Sung-Won , Konstantopoulou, Irene , Lesueur, Fabienne , Matricardi, Laura , Gomes, Denise Molina , Nevanlinna, H , Olopade, Olufunmilayo I , Palli, Domenico , Park, Sue K , Parsons, Michael T , Peterlongo, Paolo , Petersen, Annabeth Høgh , Pujana, Miquel Angel , Ruddy, Kathryn J , Scarpitta, Rosa , Shah, Payal D , Silvestri, Valentina , Southey, Melissa C , Spurdle, Amanda B , Stoppa-Lyonnet, Dominique , Sunde, Lone , Teixeira, Manuel R , Teo, Soo H , Tommasi, Stefania , Toss, Angela , van der Luijt, Rob B , Vierstraete, Jeroen , Wieme, Greet , Yadav, Siddhartha , Antoniou, Antonis C , Eccles, Diana , Weitzel, Jeffrey N , Torres, Diana , Nathanson, Katherine L , Arason, Adalgeir , Barrowdale, Daniel , Boonen, Susanne E , Cortesi, Laura , Engel, Christoph , Hahnen, Eric , Montagna, Marco , Viel, Alessandra , Simard, Jacques , Chenevix-Trench, Georgia , Ottini, Laura , Senter, Leigha , Faivre, Laurence , Rashid, Muhammad U , Calvello, Mariarosaria , Feliubadaló, Lidia , Hauke, Jan , Manoukian, Siranoush , Pomerantz, Mark M , Kwong, Ava , Lindblom, Annika , Friebel, Tara M. , Arnold, Norbert , Balmañà, Judith , Barnes, Daniel R. , Benı́tez, Javier , Bonadona, Valérie , Bonanni, Bernardo , Borg, Åke , Buys, Saundra S. , Cabezas-Camarero, Santiago , Caligo, Maria A. , Campbell, Ian , Carnevali, Ileana Wanda , Chu, Annie Tsz-Wai , Chung, Wendy K. , Cook, Jackie A , Couch, Fergus J. , Hoya, Miguel de la , Dı́ez, Orland , Domchek, Susan M. , Fostira, Florentia , Gerdes, Anne‐Marie , Godwin, Andrew K. , Herold, Natalie, Hopper, John L. , Jensen, Thomas Dyrso, Vijai, Joseph , Lasset, Christine , Lázaro, Conxi , Lemke, Johannes R. , Mai, Phuong L., Meindl, Alfons , Miller, Clare, Moserle, Lidia , Mulligan, Anna Marie , Nevanlinna, Heli , Palli, Domenico , Parsons, Michael T. , Perez-Segura, Pedro , Radice, Paolo , Rhiem, Kerstin , Robson, Mark E. , Sharma, Priyanka , Shin, Vivian Yvonne , Singer, Christian F. , Southey, Melissa C. , Spurdle, Amanda B. , Steele, Linda, Steinemann, Doris , Stoppa‐Lyonnet, Dominique , Stradella, Agostina , Tischkowitz, Marc D. , Tognazzo, Silvia , Toland, Amanda Ewart , Tung, Nadine , Asperen, Christi J. van , Luijt, Rob B. van der , Yannoukakos, Drakoulis , Neuhausen, Susan L. , Rebbeck, Timothy R.
Cancer Research | November 13, 2019 | Volume: 80 | Issue: 3 | Pages: 624-638
Abstract Pathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer. We evaluated whether PSVs in BRCA1/2 were associated with risk of overall prostate cancer or high grade (Gleason 8+) prostate cancer using an international sample of 65 BRCA1 and 171 BRCA2 male PSV carriers with prostate cancer, and 3,388 BRCA1 and 2,880 BRCA2 male PSV carriers without prostate cancer. PSVs in the 3′ region of BRCA2 (c.7914+) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001-c.7913 [HR = 1.78; 95% confidence interval (CI), 1.25–2.52; P = 0.001], as well as elevated risk of Gleason 8+ prostate cancer (HR = 3.11; 95% CI, 1.63–5.95; P = 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR = 2.83; 95% CI, 1.71–4.68; P = 0.00004) and elevated risk of Gleason 8+ prostate cancer (HR = 4.95; 95% CI, 2.12–11.54; P = 0.0002). No genotype–phenotype associations were detected for PSVs in BRCA1. These results demonstrate that specific BRCA2 PSVs may be associated with elevated risk of developing aggressive prostate cancer. Significance: Aggressive prostate cancer risk in BRCA2 mutation carriers may vary according to the specific BRCA2 mutation inherited by the at-risk individual.
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.
Genetic Data from Nearly 63,000 Women of European Descent Predicts DNA Methylation Biomarkers and Epithelial Ovarian Cancer Risk
Yang, Yaohua , Wu, Lang , Shu, Xiao-Ou , Lu, Yingchang , Beeghly‐Fadiel, Alicia, Li, Bingshan , Ye, Fei , Banerjee, Susana , Benı́tez, Javier , Chang‐Claude, Jenny , Chen, Kexin , DeFazio, Anna , Dörk, Thilo , Eccles, Diana M., Edwards, Digna Velez, Fasching, Peter A. , Fortner, Renée T. , Gayther, Simon A. , Goode, Ellen L. , Goodman, Marc T. , Heitz, Florian , Hildebrandt, Michelle A.T., Høgdall, Estrid , Høgdall, Claus , Huntsman, David G. , Kar, Siddhartha , Kelemen, Linda E. , Koushik, Anita , Lambrechts, Diether , Le, Nhu D. , Levine, Douglas A. , Massuger, Leon F.A.G. , Matsuo, Keitaro , May, Taymaa, McNeish, Iain A. , Menon, Usha , Monteiro, Álvaro N.A. , Moorman, Patricia G. , Moysich, Kirsten B. , Ness, Roberta B., Olsson, Håkan , Onland‐Moret, N. Charlotte , Park, Sue K. , Paul, James , Pearce, Celeste Leigh, Phelan, Catherine M., Pike, Malcolm C. , Ramus, Susan J. , Ríboli, Elio , Rodríguez‐Antona, Cristina , Romieu, Isabelle, Sandler, Dale P. , Schildkraut, Joellen M. , Shan, Kang, Sieh, Weiva , Stampfer, Meir J. , Sutphen, Rebecca , Swerdlow, Anthony J. , Szafron, Lukasz M. , Teo, Soo‐Hwang , Tworoger, Shelley S. , Webb, Penelope M. , Wentzensen, Nicolas , Woo, Yin Ling , Wu, Anna H. , Chenevix‐Trench, Georgia , Sellers, Thomas A. , Long, Jirong , Eccles, Diana , Lambrechts, Diether , Chen, Kexin , Shu, Xiao-Ou , Brenton, James D , Chang-Claude, Jenny , Fazio, Anna de , Dennis, Joe , Fasching, Peter A , Fortner, Renée T , Giles, Graham G , Harris, Holly R , Kiemeney, Lambertus A , Kjaer, Susanne K , Koushik, Anita , McNeish, Iain A , Menon, Usha , Monteiro, Alvaro N , Nevanlinna, H , Park, Sue K , Paul, James , Ramus, Susan J , Rodríguez-Antona, Cristina , Sandler, Dale P , Szafron, Lukasz M , Teo, Soo H , Tworoger, Shelley S , Webb, Penelope M , Wolk, Alicja , Dörk, Thilo , Lambrechts, Diether , Eccles, Diana , Swerdlow, Anthony J , Moysich, Kirsten , Matsuo, Keitaro , Heitz, Florian , Lambrechts, Diether , Sieh, Weiva , Benitez, Javier , Chenevix-Trench, Georgia , Høgdall, Estrid , Høgdall, Claus K , Kar, Siddhartha , Riboli, Elio , Goodman, Marc T , Cai, Qiuyin , Beeghly‐Fadiel, Alicia , Berchuck, Andrew , Anton‐Culver, Hoda , Bjørge, Line , Brenton, James D. , Bützow, Ralf C. , Campbell, Ian , Cook, Linda S. , Cramer, Daniel W. , Doherty, Jennifer A. , Edwards, Digna R. Velez , Giles, Graham G. , Glasspool, Rosalind , Gronwald, Jacek , Harris, Holly R. , Hildebrandt, Michelle A.T. , Karlan, Beth Y. , Kiemeney, Lambertus A. , Kjær, Susanne K. , Modugno, Francesmary , Nevanlinna, Heli , Pejovic, Tanja B. , Setiawan, Veronica Wendy , Shan, Kang, Siddiqui, Nadeem , Tyrer, Jonathan P. , White, Emily , Willett, Walter C. , Wolk, Alicja , Li, Yan , Yannoukakos, Drakoulis , Pharoah, Paul D.P. , Zheng, Wei , Yang, Yaohua
Cancer Research | December 17, 2018 | Volume: 79 | Issue: 3 | Pages: 505-517
Abstract DNA methylation is instrumental for gene regulation. Global changes in the epigenetic landscape have been recognized as a hallmark of cancer. However, the role of DNA methylation in epithelial ovarian cancer (EOC) remains unclear. In this study, high-density genetic and DNA methylation data in white blood cells from the Framingham Heart Study (N = 1,595) were used to build genetic models to predict DNA methylation levels. These prediction models were then applied to the summary statistics of a genome-wide association study (GWAS) of ovarian cancer including 22,406 EOC cases and 40,941 controls to investigate genetically predicted DNA methylation levels in association with EOC risk. Among 62,938 CpG sites investigated, genetically predicted methylation levels at 89 CpG were significantly associated with EOC risk at a Bonferroni-corrected threshold of P < 7.94 × 10−7. Of them, 87 were located at GWAS-identified EOC susceptibility regions and two resided in a genomic region not previously reported to be associated with EOC risk. Integrative analyses of genetic, methylation, and gene expression data identified consistent directions of associations across 12 CpG, five genes, and EOC risk, suggesting that methylation at these 12 CpG may influence EOC risk by regulating expression of these five genes, namely MAPT, HOXB3, ABHD8, ARHGAP27, and SKAP1. We identified novel DNA methylation markers associated with EOC risk and propose that methylation at multiple CpG may affect EOC risk via regulation of gene expression. Significance: Identification of novel DNA methylation markers associated with EOC risk suggests that methylation at multiple CpG may affect EOC risk through regulation of gene expression.
rs495139 in the TYMS-ENOSF1 Region and Risk of Ovarian Carcinoma of Mucinous Histology
Kelemen, Linda E. , Earp, Madalene A. , Chenevix‐Trench, Georgia , Group, On behalf of Australian Ovarian Cancer Study, Fasching, Peter A. , Beckmann, Matthias W. , Ekici, Arif B. , Hein, Alexander , Lambrechts, Diether , Lambrechts, Sandrina, Nieuwenhuysen, Els Van , Vergote, Ignace , Rossing, Mary Anne, Chang‐Claude, Jenny , Moysich, Kirsten, Cannioto, Rikki , Lele, Shashikant , Odunsi, Kunle , Goodman, Marc T. , Shvetsov, Yurii B. , Thompson, Pamela J., Dörk, Thilo , Antonenkova, Natalia, Bogdanova, Natalia , Hillemanns, Peter , Runnebaum, Ingo B. , Harter, Philipp , Heitz, Florian , Schwaab, Ira, Edwards, Robert P., Kelley, Joseph L., Ness, Roberta B., Lester, Jenny, Oršulić, Sandra , Walsh, Christine M. , Jensen, Allan , Cunningham, Julie M. , Vierkant, Robert A. , Bruinsma, Fiona , Hildebrandt, Michelle, Liang, Dong , Lu, Karen H., Wu, Xifeng , Sellers, Thomas A. , Schildkraut, Joellen M. , Iversen, Edwin S., Terry, Kathryn L. , Tworoger, Shelley S. , Thomsen, Liv Vestrheim, Krakstad, Camilla , Tangen, Ingvild L. , Aben, Katja K.H. , Massuger, Leon F.A.G. , Altena, Anne M. van , Bean, Yukie T., Kellar, Melissa, Le, Nhu D. , Brooks‐Wilson, Angela , Jakubowska, Anna , Lubiński, Jan , Wentzensen, Nicolas , Brinton, Louise A. , Lissowska, Jolanta , Høgdall, Estrid , Engelholm, Svend Aage, Høgdall, Claus , Lundvall, Lene, Nedergaard, Lotte , Dicks, Ed , Song, Honglin , McNeish, Iain A. , Carty, Karen , Eccles, Diana , Whittemore, Alice S. , McGuire, Valerie , Rothstein, Joseph H. , Sieh, Weiva , Narod, Steven A., Phelan, Catherine, McLaughlin, John, Ziogas, Argyrios, Menon, Usha , Gayther, Simon A. , Ramus, Susan J. , Wu, Anna H. , Pearce, Celeste Leigh, Lee, Alice W. , Pike, Malcolm C. , Kupryjańczyk, Jolanta , Podgórska, Agnieszka , Plisiecka-Hałasa, Joanna, Sawicki, Włodzimierz , Goode, Ellen L. , Berchuck, Andrew, Lu, Karen H. , Lambrechts, Diether , Earp, Madalene, Hein, Alexander , Behrens, Sabine , Hillemanns, Peter , Nevanlinna, H , Kjaer, Susanne K , Jensen, Allan , Cunningham, Julie M , Vierkant, Robert A , Bjorge, Line , Gronwald, Jacek , Brinton, Louise A , Pharoah, Paul D P , Tyrer, Jonathan P. , McNeish, Iain A , Eccles, Diana , Menon, Usha , Ramus, Susan J , Dörk, Thilo , Lambrechts, Diether , Tworoger, Shelley S , Moysich, Kirsten , Lissowska, Jolanta , Brooks-Wilson, Angela R , Heitz, Florian , Jakubowska, Anna , Kupryjanczyk, Jolanta , Lambrechts, Diether , Sieh, Weiva , Ekici, Arif B , Bogdanova, Natalia V , Chenevix-Trench, Georgia , Høgdall, Estrid , Høgdall, Claus K , Lubinski, Jan , Goodman, Marc T , Fridley, Brooke L. , Group, On behalf of Australian Ovarian Cancer Study, Doherty, Jennifer A. , Behrens, Sabine , Moysich, Kirsten B. , Wilkens, Lynne R. , Bois, Andreas du , Bützow, Ralf C. , Pelttari, Liisa M. , Nevanlinna, Heli , Modugno, Francesmary , Karlan, Beth Y. , Walsh, Christine, Kjær, Susanne K. , Giles, Graham G. , Southey, Melissa C. , Levine, Douglas A. , Cramer, Daniel W. , Poole, Elizabeth M. , Bandera, Elisa V. , Olson, Sara H. , Orlow, Irene , Thomsen, Liv Cecilie Vestrheim , Bjørge, Line , Kiemeney, Lambertus A. , Pejovic, Tanja B. , Cook, Linda S. , Gronwald, Jacek , Cybulski, Cezary , Pharoah, Paul D.P. , Siddiqui, Nadeem , Glasspool, Rosalind , Paul, James , Campbell, Ian , McLaughlin, John, Risch, Harvey A. , Anton‐Culver, Hoda , Gentry‐Maharaj, Aleksandra
International Journal of Molecular Sciences | August 21, 2018 | Volume: 19 | Issue: 9 | Pages: 2473
Thymidylate synthase (TYMS) is a crucial enzyme for DNA synthesis. TYMS expression is regulated by its antisense mRNA, ENOSF1. Disrupted regulation may promote uncontrolled DNA synthesis and tumor growth. We sought to replicate our previously reported association between rs495139 in the TYMS-ENOSF1 3′ gene region and increased risk of mucinous ovarian carcinoma (MOC) in an independent sample. Genotypes from 24,351 controls to 15,000 women with invasive OC, including 665 MOC, were available. We estimated per-allele odds ratios (OR) and 95% confidence intervals (CI) using unconditional logistic regression, and meta-analysis when combining these data with our previous report. The association between rs495139 and MOC was not significant in the independent sample (OR = 1.09; 95% CI = 0.97–1.22; p = 0.15; N = 665 cases). Meta-analysis suggested a weak association (OR = 1.13; 95% CI = 1.03–1.24; p = 0.01; N = 1019 cases). No significant association with risk of other OC histologic types was observed (p = 0.05 for tumor heterogeneity). In expression quantitative trait locus (eQTL) analysis, the rs495139 allele was positively associated with ENOSF1 mRNA expression in normal tissues of the gastrointestinal system, particularly esophageal mucosa (r = 0.51, p = 1.7 × 10−28), and nonsignificantly in five MOC tumors. The association results, along with inconclusive tumor eQTL findings, suggest that a true effect of rs495139 might be small.
Abstract 225: Tumor-infiltrating CD8-positive T-lymphocytes in tubo-ovarian high-grade serous cancer are associated with multiple germline variants in 22q12.1 in a genome-wide association analysis
Natanzon, Yanina , Armasu, Sebastian M. , McCauley, Bryan M. , Cunningham, Julie M. , Chang‐Claude, Jenny, Fasching, Peter A. , Goodman, Marc T. , Moysich, Kirsten B. , Ness, Roberta B., Goode, Ellen L. , Goodman, Marc T , Köbel, Martin , Winham, Stacey J. , Vierkant, Robert A. , Bowtell, David D.L. , Campbell, Ian , DeFazio, Anna , Karlan, Beth Y. , Modugno, Francesmary , Sieh, Weiva , Pharoah, Paul D.P. , Ramus, Susan J.
Cancer Research | August 17, 2018 | Volume: 78 | Issue: 13_Supplement | Pages: 225-225
Abstract Tubo-ovarian high-grade serous cancer (HGSC) is the most common histotype of epithelial ovarian cancer (70%-80%) and the leading cause of death from gynecological malignancy. Novel monoclonal antibody and adoptive cell transfer immunotherapies have found success in cancer in the past five years; however success in HGSC treatment has been elusive thus far. We have recently shown that CD8+ T-lymphocytes infiltrating the tumor proper (TILs) associate in a dose response manner with longer patient survival time regardless of age, stage or residual disease. As understanding host factors associated with this clinically relevant tumor phenotype will contribute to the development of targeted therapies, we sought to identify germline genetic factors associated with CD8+ TIL levels in HGSC. We performed a germline genome-wide association study (GWAS) of CD8+ TILs using 1204 HGSC patients of European ancestry from twelve studies with centralized genotyping, immunohistochemistry, and harmonization of clinical data. Germline genotypes were assayed using the Illumina Infinium OncoArray Beadchip and were imputed to over 11.4 million variants based on the 1000 Genomes Project reference panel. CD8 immunohistochemistry was performed on tissue microarrays using the Leica Bond Rx stainer and scored into four levels of CD8+ TILs per x400 magnification of a 0.55-mm diameter field for each tumor hotspot: none (no CD8+ TILs), low (1-2 CD8+ TILs), moderate (3-19 CD8+ TILs), high (20 or more CD8+ TILs). GWAS used multinomial regression modelling of these four CD8+ TIL levels adjusted for study site, age, and European ancestry principal components. On the average, CD8+ TIL levels were 18%, 19%, 44% and 18% for none, low, moderate and high levels, respectively. As expected, CD8+ TIL levels associated with overall survival time (p < 2.6x10-8), and CD8+ TIL levels and age at diagnosis were similarly distributed across study sites. We identified a region on chromosome 22 with multiple, correlated variants (MAF > 20%) associated with CD8+ TIL levels at p-value < 2.0x10-5. The most statistically significant variant was an indel (rs557925408) located in the an intron of the MYO18B gene (Myosin XVIIIB, p-value < 8.7x10-6). Each copy of this variant associated with a reduced extent of CD8+ TIL infiltration (OR low v none = 0.92; OR moderate v none = 0.61). An independent set of 1200 OncoArray genotyped HGSC cases are undergoing CD8+ TIL scoring in December 2017 and will be included in final genome-wide analysis. This will provide improved statistical power and enable consideration of additional genetic models (e.g., linear trend tests). Comprehensive integrative analysis of germline, tumor, and clinical features provides a model for clinical molecular epidemiology studies and will be key to increasing our understanding of this important HGSC immunophenotype. Citation Format: Yanina Natanzon, Martin Köbel, Stacey J. Winham, Sebastian M. Armasu, Bryan M. McCauley, Robert A. Vierkant, Julie M. Cunningham, David Bowtell, Ian G. Campbell, Jenny Chang-Claude, Anna deFazio, Peter A. Fasching, Mark T. Goodman, Beth Y. Karlan, Francesmary Modugno, Kirsten B. Moysich, Roberta B. Ness, Weiva Sieh, Paul D. Pharoah, Susan J. Ramus, Ellen L. Goode. Tumor-infiltrating CD8-positive T-lymphocytes in tubo-ovarian high-grade serous cancer are associated with multiple germline variants in 22q12.1 in a genome-wide association analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 225.
A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk
Lu, Yingchang , Beeghly‐Fadiel, Alicia, Wu, Lang , Li, Bingshan , Schildkraut, Joellen M. , Im, Hae Kyung , Chen, Y. Ann , Permuth, Jennifer B. , Reid, Brett M. , Teer, Jamie K. , Moysich, Kirsten B., Andrulis, Irene L. , Barkardóttir, Rósa B. , Benı́tez, Javier , Caldés, Trinidad , Chang‐Claude, Jenny , Claes, Kathleen , Daly, Mary B., DeFazio, Anna , Dörk, Thilo , Easton, Douglas F. , Eccles, Diana M., Fasching, Peter A. , Fortner, Renée T. , Fountzilas, George , Friedman, Eitan , Ganz, Patricia A. , Goldgar, David E., Goodman, Marc T. , Greene, Mark H. , Hamann, Ute, Heitz, Florian , Hildebrandt, Michelle A.T., Høgdall, Claus , Hulick, Peter J. , Huntsman, David G. , Imyanitov, Evgeny N., Jakubowska, Anna , James, Paul A. , Kelemen, Linda E., Kwong, Ava , Le, Nhu D., Lesueur, Fabienne , May, Taymaa, McGuffog, Lesley, McNeish, Iain A. , Merritt, Melissa A. , Montagna, Marco , Ņikitina-Zaķe, Liene , Offit, Kenneth, Oláh, Edith , Olopade, Olufunmilayo I. , Olsson, Håkan , Osório, Ana , Park, Sue K. , Peeters, Petra H.M. , Peterlongo, Paolo , Phelan, Catherine M., Pujana, Miguel Ángel , Ramus, Susan J. , Rennert, Gad , Rodriguez, Gustavo C. , Rodríguez‐Antona, Cristina , Romieu, Isabelle , Rookus, Matti A. , Rossing, Mary Anne, Rzepecka, Iwona K. , Schmutzler, Rita K., Sieh, Weiva , Simard, Jacques , Song, Honglin , Sutphen, Rebecca , Swerdlow, Anthony J. , Teixeira, Manuel R. , Teo, Soo‐Hwang , Thomassen, Mads , Trichopoulou, Antonia , Tworoger, Shelley S. , Rensburg, Elizabeth J. van , Vega, Ana , Edwards, Digna Velez, Webb, Penelope M. , Weitzel, Jeffrey N. , Wentzensen, Nicolas , Wu, Anna H. , Zorn, Kristin K. , Gayther, Simon A. , Antoniou, Antonis C. , Goode, Ellen L. , Chenevix‐Trench, Georgia , Sellers, Thomas A. , Long, Jirong , Durocher, Francine , Eccles, Diana , Permuth, Jennifer B , Teer, Jamie K , Barnes, Daniel R , Caldes, Trinidad , Caligo, Maria A , Chang-Claude, Jenny , Fazio, Anna de , Dennis, Joe , Fasching, Peter A , Fortner, Renée T , Garber, J. E. , Giles, Graham G , Greene, Mark H , Hulick, Peter J , Isaacs, Claudine , James, Paul , Kiemeney, Lambertus A , Kjaer, Susanne K , Leslie, Goska , Lesueur, Fabienne , McNeish, Iain A , Nevanlinna, H , Nussbaum, Robert , Park, Sue K , Parsons, Michael T , Peterlongo, Paolo , Pujana, Miquel Angel , Ramus, Susan J , Rennert, Gad , Rodríguez-Antona, Cristina , Sandler, Dale P , Spurdle, Amanda B , Teixeira, Manuel R , Teo, Soo H , Tworoger, Shelley S , van Rensburg, Elizabeth J , Vanderstichele, Adriaan , Webb, Penelope M , Wolk, Alicja , Dörk, Thilo , Eccles, Diana , Swerdlow, Anthony J , Moysich, Kirsten , Vega, Ana , Weitzel, Jeffrey N , Claes, Kathleen B M , Olopade, Olufunmilayo I , Heitz, Florian , Jakubowska, Anna , Sieh, Weiva , Benitez, Javier , Montagna, Marco , Simard, Jacques , Chenevix-Trench, Georgia , Høgdall, Claus K , Goodman, Marc T , Beeghly‐Fadiel, Alicia , Guo, Xingyi , Moysich, Kirsten B. , Anton‐Culver, Hoda , Arun, Banu , Bandera, Elisa V. , Barnes, Daniel R. , Bjørge, Line , Brenton, James D. , Bützow, Ralf C. , Caligo, Maria A. , Campbell, Ian , Couch, Fergus J. , Cramer, Daniel W. , Dı́ez, Orland , Domchek, Susan M. , Garber, Judy E. , Giles, Graham G. , Godwin, Andrew K. , Gronwald, Jacek , Hildebrandt, Michelle A.T. , Hollestelle, Antoinette , Isaacs, Claudine , Karlan, Beth Y. , Kiemeney, Lambertus A. , Kjær, Susanne K. , Leslie, Goska , Levine, Douglas A. , Mattiello, Amalia , Modugno, Francesmary , Neuhausen, Susan L. , Nevanlinna, Heli , Nielsen, Finn Cilius , Nussbaum, Robert L. , Olson, Sara H. , Parsons, Michael T. , Pejovic, Tanja B. , Risch, Harvey A. , Sandler, Dale P. , Setiawan, Veronica Wendy , Sharma, Priyanka , Singer, Christian F. , Southey, Melissa C. , Spurdle, Amanda B. , Tischkowitz, Marc D. , Toland, Amanda Ewart , Tung, Nadine , Vanderstichele, Adriaan , Edwards, Digna R. Velez , White, Emily , Wolk, Alicja , Yannoukakos, Drakoulis , Berchuck, Andrew , Pharoah, Paul D.P. , Zheng, Wei , Kwong, Ava , Im, H K
Cancer Research | July 27, 2018 | Volume: 78 | Issue: 18 | Pages: 5419-5430
Abstract Large-scale genome-wide association studies (GWAS) have identified approximately 35 loci associated with epithelial ovarian cancer (EOC) risk. The majority of GWAS-identified disease susceptibility variants are located in noncoding regions, and causal genes underlying these associations remain largely unknown. Here, we performed a transcriptome-wide association study to search for novel genetic loci and plausible causal genes at known GWAS loci. We used RNA sequencing data (68 normal ovarian tissue samples from 68 individuals and 6,124 cross-tissue samples from 369 individuals) and high-density genotyping data from European descendants of the Genotype-Tissue Expression (GTEx V6) project to build ovarian and cross-tissue models of genetically regulated expression using elastic net methods. We evaluated 17,121 genes for their cis-predicted gene expression in relation to EOC risk using summary statistics data from GWAS of 97,898 women, including 29,396 EOC cases. With a Bonferroni-corrected significance level of P < 2.2 × 10−6, we identified 35 genes, including FZD4 at 11q14.2 (Z = 5.08, P = 3.83 × 10−7, the cross-tissue model; 1 Mb away from any GWAS-identified EOC risk variant), a potential novel locus for EOC risk. All other 34 significantly associated genes were located within 1 Mb of known GWAS-identified loci, including 23 genes at 6 loci not previously linked to EOC risk. Upon conditioning on nearby known EOC GWAS-identified variants, the associations for 31 genes disappeared and three genes remained (P < 1.47 × 10−3). These data identify one novel locus (FZD4) and 34 genes at 13 known EOC risk loci associated with EOC risk, providing new insights into EOC carcinogenesis. Significance: Transcriptomic analysis of a large cohort confirms earlier GWAS loci and reveals FZD4 as a novel locus associated with EOC risk. Cancer Res; 78(18); 5419–30. ©2018 AACR.
Height and Body Mass Index as Modifiers of Breast Cancer Risk in BRCA1/2 Mutation Carriers: A Mendelian Randomization Study
Qian, Frank , Wang, Shengfeng , McGuffog, Lesley, Barrowdale, Daniel , Oosterwijk, Jan C., Evans, D. Gareth , Engel, Christoph , Kast, Karin, Aalfs, Cora M. , Adank, Muriel A. , Agnarsson, Bjarni A. , Aittomäki, Kristiina, Alducci, Elisa, Andrulis, Irene L. , Ausems, Margreet G.E.M. , Azzollini, Jacopo , Barouk-Simonet, Emmanuelle, Belotti, Muriel, Benı́tez, Javier , Berger, Andreas, Borg, Åke , Bradbury, Angela R. , Brunet, Joan , Caldés, Trinidad , Caputo, Sandrine M. , Chiquette, Jocelyne , Collée, J. Margriet, Coupier, Isabelle, Daly, Mary B., Davidson, Rosemarie, Donaldson, Alan, Dorfling, Cecilia M., Eeles, Rosalind A. , Feliubadaló, Lídia , Foretová, Lenka , Fowler, Jeffrey M., Friedman, Eitan , Frost, Debra, Ganz, Patricia A. , García‐Barberán, Vanesa , Glendon, Gord , Gómez, E. , Hahnen, Eric , Hamann, Ute, Henderson, Alex, Hendricks, Carolyn B., Hulick, Peter J. , Imyanitov, Evgeny N., Izatt, Louise , Jakubowska, Anna , Kaczmarek, Katarzyna, Kang, Eunyoung , Kets, Carolien M., Kim, Sung-Won, Kwong, Ava , Laitman, Yael , Lasset, Christine, Lee, Min Hyuk , Lee, Jong Won, Lee, Jihyoun , Lester, Jenny, Lesueur, Fabienne , Loud, Jennifer T. , Mebirouk, Noura, Meijers‐Heijboer, Hanne , Meindl, Alfons , Montagna, Marco , Mooij, Thea M. , Mouret‐Fourme, Emmanuelle, Nathanson, Katherine L. , Niederacher, Dieter , Offit, Kenneth, Oláh, Edith , Ong, Kai-Ren, Ottini, Laura , Park, Sue K. , Peterlongo, Paolo , Pfeiler, Georg , Phelan, Catherine M., Poppe, Bruce , Pradhan, Nisha , Radice, Paolo , Ramus, Susan J. , Rantala, Johanna, Rodriguez, Gustavo C. , Schmutzler, Rita K., Selkirk, Christina G. , Shah, Payal D. , Simard, Jacques , Sutter, Christian , Tan, Yen Y. , Teixeira, R , Teo, Soo‐Hwang , Terry, Mary Beth , Thomassen, Mads , Toland, Amanda Ewart, Tucker, Kathy , Engelen, Klaartje van , Rensburg, Elizabeth J. van , Wang‐Gohrke, Shan , Wappenschmidt, Barbara , Weitzel, Jeffrey N. , Collaborators, GEMO Study, HEBON, EMBRACE, Greene, Mark H. , Rookus, Matti A. , Easton, Douglas F. , Chenevix‐Trench, Georgia , Antoniou, Antonis C. , Goldgar, David E., Olopade, Olufunmilayo I. , Huo, Dezheng , Durocher, Francine , Teixeira, Manuel R. , Mitchell, Jonathan A. , Białkowska, Katarzyna , Hulick, Peter J , Lesueur, Fabienne , Peterlongo, Paolo , Ramus, Susan J , Teixeira, Manuel R , Teo, Soo H , van Rensburg, Elizabeth J , Radice, Paolo , Weitzel, Jeffrey N , Azzollini, Jacopo , Brunet, Joan , Eeles, Rosalind A , Evans, D Gareth , Olopade, Olufunmilayo I , Jakubowska, Anna , Nathanson, Katherine L , Barrowdale, Daniel , Benitez, Javier , Engel, Christoph , Montagna, Marco , Simard, Jacques , Chenevix-Trench, Georgia , Ottini, Laura , Mitchell, Jonathan S. , Leslie, Goska , Chung, Wendy K. , Adlard, Julian , Arun, Banu , Barwell, Julian , Borg, Åke , Buys, Saundra S. , Caligo, Maria A. , Campbell, Ian , Claes, Kathleen , Couch, Fergus J. , Dı́ez, Orland , Domchek, Susan M. , Garber, Judy E. , Godwin, Andrew K. , Gronwald, Jacek , Hopper, John L. , Isaacs, Claudine , Izquierdo, Á. , Karlan, Beth Y. , Kim, Sung-Won , Lasset, Christine , Lubiński, Jan , Meindl, Alfons , Miller, Austin , Morrison, Patrick J. , Neuhausen, Susan L. , Nevanlinna, Heli , Nielsen, Finn Cilius , Nussbaum, Robert L. , Robson, Mark E. , Singer, Christian F. , Giles, Graham G , Stoppa‐Lyonnet, Dominique , Tischkowitz, Marc D. , Toland, Amanda Ewart , Tung, Nadine , Asperen, Christi J. van , Yannoukakos, Drakoulis , Collaborators, GEMO Study, HEBON, EMBRACE, Rebbeck, Timothy R. , Feliubadaló, Lidia , Gómez-García, Encarna B , Terry, Mary Beth , Kwong, Ava
JNCI: Journal of the National Cancer Institute | July 3, 2018 | Volume: 111 | Issue: 4 | Pages: 350-364
Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations
Friebel, Tara M. , Friedman, Eitan , Hamann, Ute, Huo, Dezheng , Kwong, Ava , Oláh, Edith , Olopade, Olufunmilayo I., Solano, Ángela R. , Teo, Soo‐Hwang , Thomassen, Mads , Weitzel, Jeffrey N. , Chan, TL, Couch, Fergus J., Goldgar, David E., Kruse, Torben A., Palmero, Edenir Inêz , Park, Sue K. , Torres, Diana , Rensburg, Elizabeth J. van , McGuffog, Lesley, Aalfs, Cora M. , Abugattas, Julio E. , Aittomäki, Kristiina, Andrews, Lesley , Andrulis, Irene L., Arason, Aðalgeir , Arun, Banu, Asseryanis, Ella, Auerbach, Leo, Azzollini, Jacopo , Balmañà, Judith , Barile, Monica, Barkardóttir, Rósa B. , Barrowdale, Daniel , Benı́tez, Javier , Berger, Andreas, Berger, Raanan , Blanco, Amie , Blazer, Kathleen R. , Blok, Marinus J. , Bonadona, Valérie , Bradbury, Angela R. , Brewer, Carole, Buecher, Bruno , Caldés, Trinidad, Caliebe, Almuth , Caligo, Maria A. , Caputo, Sandrine M. , Chiquette, Jocelyne , Claes, Kathleen , Collée, J. Margriet, Davidson, Rosemarie, Hoya, Miguel de la , Leeneer, Kim De , Pauw, Antoine De , Delnatte, Capucine, Ding, Yuan Chun , Ditsch, Nina , Dorfling, Cecilia M., Dworniczak, Bernd , Eason, Jacqueline , Easton, Douglas F. , Eeles, Rosalind A. , Ehrencrona, Hans , Ejlertsen, Bent , EMBRACE, Engel, Christoph , Engert, Stefanie, Evans, D. Gareth , Faivre, Laurence, Feliubadaló, Lídia , Ferrer, Sandra Fert, Foretová, Lenka , Fowler, Jeffrey M., Frost, Debra, Galvão, Henrique C.R. , Ganz, Patricia A. , Gauthier‐Villars, Marion , Gehrig, Andrea, Collaborators, GEMO Study, Gerdes, Anne‐Marie , Gesta, Paul , Giannini, Giuseppe , Giraud, Sophie , Glendon, Gord , Godwin, Andrew K., Greene, Mark H. , Gutierrez‐Barrera, Angelica M. , Hahnen, Eric , Hauke, Jan , HEBON, Henderson, Alex, Hogervorst, Frans B. L., Honisch, Ellen, Imyanitov, Evgeny N., Izatt, Louise , Izquierdo, Á. , Jakubowska, Anna , James, Paul A. , Janavičius, Ramūnas , Jensen, Uffe Birk , Vijai, Joseph , Kaczmarek, Katarzyna, Karlan, Beth Y., Kast, Karin, Investigators, kConFab, Kim, Sung-Won, Konstantopoulou, Irene , Korach, Jacob, Laitman, Yael , Lasset, Christine, Lázaro, Conxi , Lee, Annette, Lee, Min Hyuk , Lester, Jenny, Lesueur, Fabienne , Liljegren, Annelie, Lindor, Noralane M. , Longy, Michel, Loud, Jennifer T. , Lu, Karen H. , Lubiński, Jan , Macháčková, Eva , Manoukian, Siranoush , Mari, Véronique , Martínez-Bouzas, Cristina, Mátrai, Zoltán , Mebirouk, Noura, Meijers‐Heijboer, Hanne , Meindl, Alfons , Mensenkamp, Arjen R. , Mickys, Ugnius, Montagna, Marco , Moysich, Kirsten B., Mulligan, Anna Marie , Musinsky, Jacob, Ngeow, Joanne , Niederacher, Dieter , Nielsen, Henriette Roed, Nielsen, Finn C., Offit, Kenneth, Öfverholm, Anna , Ong, Kai‐Ren , Osório, Ana , Papp, J., Pasini, Barbara , Pedersen, Inge Søkilde , Peixoto, Ana , Peruga, Nina, Peterlongo, Paolo , Pohl, Esther, Pradhan, Nisha , Prajzendanc, Karolina , Prieur, Fabienne, Radice, Paolo , Ramus, Susan J. , Rantala, Johanna, Rashid, Muhammad Usman , Rhiem, Kerstin, Rodriguez, Gustavo C. , Rogers, Mark T., Rudaitis, Vilius , Schmidt, Ane Yde , Schmutzler, Rita K., Senter, Leigha , Shah, Payal D. , Side, Lucy, Simard, Jacques , Skytte, Anne‐Bine , Slavin, Thomas P. , Snape, Katie , Sobol, Hagay, Southey, Melissa C. , Sukiennicki, Grzegorz, Sutter, Christian , Tan, Yen Y. , Teixeira, Manuel R. , Terry, Mary Beth , Teulé, Àlex , Thomas, Abigail, Thull, Darcy L. , Tognazzo, Silvia , Toland, Amanda Ewart, Topka, Sabine , Trainer, Alison H. , Hout, Annemieke H. van der, Kolk, Lizet E. van der, Luijt, Rob B. van der , Heetvelde, Mattias Van , Varesco, Liliana, Varon‐Mateeva, Raymonda, Vega, Ana , Villarreal‐Garza, Cynthia , Wachenfeldt, Anna von , Walker, Lisa, Wang‐Gohrke, Shan , Wappenschmidt, Barbara, Yoon, Sook-Yee, Zanzottera, Cristina, Zidan, Jamal, Zorn, Kristin K. , Selkirk, Christina G. , Hulick, Peter J. , Chenevix‐Trench, Georgia , Antoniou, Antonis C. , Nathanson, Katherine L. , Durocher, Francine , Olopade, Olufunmilayo I. , Faivre, Laurence , Białkowska, Katarzyna , Caligo, Maria A , Hulick, Peter J , James, Paul , Lesueur, Fabienne , Peterlongo, Paolo , Ramus, Susan J , Teixeira, Manuel R , Teo, Soo H , van Rensburg, Elizabeth J , Moysich, Kirsten , Vega, Ana , de la Hoya, Miguel , Radice, Paolo , Weitzel, Jeffrey N , Claes, Kathleen B M , Azzollini, Jacopo , Eeles, Rosalind A , Ehrencrona, Hans , Evans, D Gareth , Joseph, Vijai , Konstantopoulou, Irene , Olopade, Olufunmilayo I , Southey, Melissa C , van der Luijt, Rob B , Jakubowska, Anna , Palmero, Edenir I , Torres, Diana , Nathanson, Katherine L , Arason, Adalgeir , Barrowdale, Daniel , Benitez, Javier , Engel, Christoph , Izquierdo, Angel , Lazaro, Conxi , Montagna, Marco , Simard, Jacques , Chenevix-Trench, Georgia , Senter, Leigha , Topka, Sabine , Rebbeck, Timothy R. , Couch, Fergus J. , Parsons, Michael T. , Leslie, Goska , Adlard, Julian , Agata, Simona , Arnold, Norbert , Bonanni, Bernardo , Buys, Saundra S. , Campbell, Ian , Chung, Wendy K. , Cook, Jackie A , Dı́ez, Orland , Domchek, Susan M. , Velázquez, Carolina , EMBRACE, Garber, Judy E. , Collaborators, GEMO Study, Gronwald, Jacek , HEBON, Hentschel, Julia , Hogervorst, Frans B.L., Isaacs, Claudine , John, Esther M. , Karlan, Beth Y. , Lasa, Adriana , Lasset, Christine , Liljegren, Annelie , Meindl, Alfons , Miller, Austin , Moysich, Kirsten B. , Neuhausen, Susan L. , Nevanlinna, Heli , Nguyen, Huu Phuc , Nussbaum, Robert L. , Papi, Laura , Pujol, Pascal , Rhiem, Kerstin , Robson, Mark E. , Sharma, Priyanka , Singer, Christian F. , Sobol, Hagay , Steele, Linda Roslyn , Steinemann, Doris , Szabo, Csilla I. , Tischkowitz, Marc D. , Toland, Amanda Ewart , Tung, Nadine , Asperen, Christi J. van , Varesco, Liliana , Varon-Mateeva, Raymonda, Wappenschmidt, Barbara , Weber, Bernhard H. F. , Yannoukakos, Drakoulis , Spurdle, Amanda B. , Faivre, Laurence , Rashid, Muhammad U , De Leeneer, Kim , Feliubadaló, Lidia , Hauke, Jan , Pasini, Barbara , Ngeow, Joanne , Manoukian, Siranoush , Lubinski, Jan , Terry, Mary Beth , Villarreal-Garza, Cynthia , Balmaña, Judith , Kwong, Ava
Human Mutation | February 15, 2018 | Volume: 39 | Issue: 5 | Pages: 593-620
Dose-Response Association of CD8 + Tumor-Infiltrating Lymphocytes and Survival Time in High-Grade Serous Ovarian Cancer
Goode, Ellen L. , Block, Matthew S. , Kalli, Kimberly R., Vierkant, Robert A. , Fogarty, Zachary C. , Tołoczko, Aleksandra, Hein, Alexander , Bouligny, Aliecia L., Jensen, Allan , Osório, Ana , Ryan, Andy , Magliocco, Anthony M., Hartmann, Arndt , Gao, Bo , McCauley, Bryan M. , Kennedy, Catherine J. , Karpinskyj, Chloe , Sousa, Christiani Bisinoto de, Tiezzi, Daniel Guimarães , Wachter, David L., Herpel, Esther , Taran, Florin‐Andrei , Nelson, Gregg , Menkiszak, Janusz , Alsop, Jennifer , Lester, Jenny , García-Donás, Jesús , Nation, Jill, Hung, Jillian A., Palacios, José , Rothstein, Joseph H. , Kelley, Joseph L., Andrade, Jurandyr Moreira de , Robles-Díaz, Luis, Intermaggio, Maria P., Widschwendter, Martin , Beckmann, Matthias W. , Ruebner, Matthias , Jimenez‐Liñan, Mercedes , Singh, Naveena , Oszurek, Oleg, Harnett, Paul R. , Rambau, Peter , Sinn, Hans‐Peter , Wagner, Philipp , Sharma, Raghwa , Ness, Roberta B., Oršulić, Sandra , Johnatty, Sharon E., Longacre, Teri A. , Eilber, Ursula, McGuire, Valerie , Sieh, Weiva , Natanzon, Yanina , Li, Zheng , Whittemore, Alice S. , DeFazio, Anna , Staebler, Annette , Bowtell, David D.L. , Høgdall, Estrid , Reis, Francisco José Cândido dos , Steed, Helen , Campbell, Ian , Benı́tez, Javier , Koziak, Jennifer M. , Chang‐Claude, Jenny, Moysich, Kirsten B. , Kelemen, Linda E. , Goodman, Marc T. , García, María J. , Fasching, Peter A. , Kommoss, Stefan , Deen, Suha , Menon, Usha , Chenevix‐Trench, Georgia , Huntsman, David G. , Köbel, Martin , Ramus, Susan J. , Winham, Stacey J. , Fazio, Anna de , Ramus, Susan J , Köbel, Martin , Hein, Alexander , Jensen, Allan , Vierkant, Robert A , Menon, Usha , Moysich, Kirsten , Campbell, Ian G , García-Donas, Jesús , Kennedy, Catherine J , Menkiszak, Janusz , Sinn, Peter , Widschwendter, Martin , Fogarty, Zachary C , Sieh, Weiva , Benitez, Javier , Chenevix-Trench, Georgia , Høgdall, Estrid , Bowtell, David D , Chen, Wenqian , Gentry‐Maharaj, Aleksandra , Bouligny, Aliecia, Hartkopf, Andreas D , Chudecka-Glaz, Anita Monika , Jung, Audrey , Hernandez, Brenda Y. , Fridley, Brooke L. , Wang, Chen , Modugno, Francesmary , Lubiński, Jan , Robles-Díaz, Luis, Ghatage, Prafull , Edwards, Todd , Brucker, Sara Yvonne , Karlan, Beth Y. , Gilks, C. Blake , Gronwald, Jacek , Cook, Linda S. , Kjær, Susanne K. , Brenton, James D. , Pharoah, Paul D.P. , Nelson, Gregg S , Harnett, Paul R , Steed, Helen , Goodman, Marc T
JAMA Oncology | October 19, 2017 | Volume: 3 | Issue: 12 | Pages: e173290
No Evidence That Genetic Variation in the Myeloid-Derived Suppressor Cell Pathway Influences Ovarian Cancer Survival
Sucheston‐Campbell, Lara, Cannioto, Rikki , Clay‐Gilmour, Alyssa , Etter, John Lewis , Eng, Kevin H., Liu, Song , Battaglia, Sebastiano , Szender, J. Brian, Minlikeeva, Albina N. , Joseph, Janine M. , Mayor, Paul , Abrams, Scott I. , Wallace, Paul K. , Soh, Kah Teong , Zsíros, Emese , Beckmann, Matthias W. , Bruegl, Amanda , Campbell, Ian , Campbell, Shawn, Chenevix‐Trench, Georgia , Diergaarde, Brenda , Doerk, Thilo, Eccles, Diana , Engelholm, Svend Aage, Fasching, Peter A. , Gayther, Simon A. , Goodman, Marc T. , Harter, Philipp , Hein, Alexander , Heitz, Florian , Hillemmanns, Peter, Høgdall, Claus , Høgdall, Estrid , Huzarski, Tomasz , Jensen, Allan , Johnatty, Sharon E. , Jung, Audrey , Klapdor, Reudiger, Kluz, Tomasz , Konopka, Bożena , Kupryjańczyk, Jolanta , Lambrechts, Diether , Lester, Jenny, Lubiński, Jan , Levine, Douglas A. , Lundvall, Lene, McGuire, Valerie , McNeish, Iain A. , Menon, Usha , Ness, Roberta B., Oršulić, Sandra , Pearce, Celeste Leigh, Ramus, Susan J. , Rothstein, Joseph H. , Rossing, Mary Anne, Rübner, Matthias, Schildkraut, Joellen M. , Schmalfeldt, Barbara , Schwaab, Ira, Sieh, Weiva , Sobiczewski, Piotr , Song, Honglin , Terry, Kathryn L. , Nieuwenhuysen, Els Van , Vanderstichele, Adriaan , Vergote, Ignace , Walsh, Christine , Webb, Penelope M. , Wentzensen, Nicolas , Whittemore, Alice S. , Wu, Anna H. , Odunsi, Kunle , Chang‐Claude, Jenny , Goode, Ellen L. , Moysich, Kirsten B. , Dörk, Thilo , Bowtell, David D.L. , Lambrechts, Diether , Clay, Alyssa I, Hu, Qiang , Segal, Brahm H. , Anton‐Culver, Hoda , Bandera, Elisa V. , Berchuck, Andrew , Bjørge, Line , Cramer, Daniel W. , Dansonka‐Mieszkowska, Agnieszka , Dao, Fanny , Doherty, Jennifer A. , Bois, Andreas du , Gentry‐Maharaj, Aleksandra , Glasspool, Rosalind , Gronwald, Jacek , Karlan, Beth Y. , Kjær, Susanne K. , Modugno, Francesmary , Paul, James , Pejovic, Tanja B. , Pharoah, Paul D.P. , Siddiqui, Nadeem , Ziogas, Argyrios , Dörk, Thilo , Lambrechts, Diether , McNeish, Iain A , Ramus, Susan J , Vanderstichele, Adriaan , Webb, Penelope M , Hein, Alexander , Jensen, Allan , Eccles, Diana , Menon, Usha , Moysich, Kirsten , Campbell, Ian G , Heitz, Florian , Kupryjanczyk, Jolanta , Lambrechts, Diether , Sieh, Weiva , Chenevix-Trench, Georgia , Høgdall, Estrid , Høgdall, Claus K , Huzarski, Tomasz , Jung, Audrey Y , Bowtell, David D , Diergaarde, Brenda , Lubinski, Jan , Kluz, Tomasz , Goodman, Marc T
Cancer Epidemiology, Biomarkers & Prevention | September 28, 2016 | Volume: 26 | Issue: 3 | Pages: 420-424
Abstract Background: The precise mechanism by which the immune system is adversely affected in cancer patients remains poorly understood, but the accumulation of immunosuppressive/protumorigenic myeloid-derived suppressor cells (MDSCs) is thought to be a prominent mechanism contributing to immunologic tolerance of malignant cells in epithelial ovarian cancer (EOC). To this end, we hypothesized genetic variation in MDSC pathway genes would be associated with survival after EOC diagnoses. Methods: We measured the hazard of death due to EOC within 10 years of diagnosis, overall and by invasive subtype, attributable to SNPs in 24 genes relevant in the MDSC pathway in 10,751 women diagnosed with invasive EOC. Versatile Gene-based Association Study and the admixture likelihood method were used to test gene and pathway associations with survival. Results: We did not identify individual SNPs that were significantly associated with survival after correction for multiple testing (P < 3.5 × 10−5), nor did we identify significant associations between the MDSC pathway overall, or the 24 individual genes and EOC survival. Conclusions: In this well-powered analysis, we observed no evidence that inherited variations in MDSC-associated SNPs, individual genes, or the collective genetic pathway contributed to EOC survival outcomes. Impact: Common inherited variation in genes relevant to MDSCs was not associated with survival in women diagnosed with invasive EOC. Cancer Epidemiol Biomarkers Prev; 26(3); 420–4. ©2016 AACR.