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1. Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci

Author: Schumacher, Fredrick R, Al Olama, Ali Amin, Berndt, Sonja I, Benlloch, Sara, Ahmed, Mahbubl, Saunders, Edward J, Dadaev, Tokhir, Leongamornlert, Daniel, Anokian, Ezequiel, Cieza-Borrella, Clara, Goh, Chee, Brook, Mark N, Sheng, Xin, Fachal, Laura, Dennis, Joe, Tyrer, Jonathan, Muir, Kenneth, Lophatananon, Artitaya, Stevens, Victoria L, Gapstur, Susan M, Carter, Brian D, Tangen, Catherine M, Goodman, Phyllis J, Thompson, Ian M, Batra, Jyotsna, Chambers, Suzanne, Moya, Leire, Clements, Judith, Horvath, Lisa, Tilley, Wayne, Risbridger, Gail P, Gronberg, Henrik, Aly, Markus, Nordström, Tobias, Pharoah, Paul, Pashayan, Nora, Schleutker, Johanna, Tammela, Teuvo LJ, Sipeky, Csilla, Auvinen, Anssi, Albanes, Demetrius, Weinstein, Stephanie, Wolk, Alicja, Håkansson, Niclas, West, Catharine ML, Dunning, Alison M, Burnet, Neil, Mucci, Lorelei A, Giovannucci, Edward, Andriole, Gerald L, Cussenot, Olivier, Cancel-Tassin, Géraldine, Koutros, Stella, Beane Freeman, Laura E, Sorensen, Karina Dalsgaard, Orntoft, Torben Falck, Borre, Michael, Maehle, Lovise, Grindedal, Eli Marie, Neal, David E, Donovan, Jenny L, Hamdy, Freddie C, Martin, Richard M, Travis, Ruth C, Key, Tim J, Hamilton, Robert J, Fleshner, Neil E, Finelli, Antonio, Ingles, Sue Ann, Stern, Mariana C, Rosenstein, Barry S, Kerns, Sarah L, Ostrer, Harry, Lu, Yong-Jie, Zhang, Hong-Wei, Feng, Ninghan, Mao, Xueying, Guo, Xin, Wang, Guomin, Sun, Zan, Giles, Graham G, Southey, Melissa C, MacInnis, Robert J, FitzGerald, Liesel M, Kibel, Adam S, Drake, Bettina F, Vega, Ana, Gómez-Caamaño, Antonio, Szulkin, Robert, Eklund, Martin, Kogevinas, Manolis, Llorca, Javier, Castaño-Vinyals, Gemma, Penney, Kathryn L, Stampfer, Meir, Park, Jong Y, Sellers, Thomas A, Lin, Hui-Yi, Stanford, Janet L, and Cybulski, Cezary
Subjects: Cancer, Aging, Prostate Cancer, Genetics, Urologic Diseases, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Case-Control Studies, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Polymorphism, Single Nucleotide, Prostatic Neoplasms, Risk, Profile Study, Australian Prostate Cancer BioResource, IMPACT Study, Canary PASS Investigators, Breast and Prostate Cancer Cohort Consortium, PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium, Cancer of the Prostate in Sweden, Prostate Cancer Genome-wide Association Study of Uncommon Susceptibility Loci, Genetic Associations and Mechanisms in Oncology (GAME-ON)/Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE) Consortium, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract: Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10-9; T>G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55-2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04-6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa1.
Published: 2018

2. Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Author: Dadaev, Tokhir, Saunders, Edward J, Newcombe, Paul J, Anokian, Ezequiel, Leongamornlert, Daniel A, Brook, Mark N, Cieza-Borrella, Clara, Mijuskovic, Martina, Wakerell, Sarah, Olama, Ali Amin Al, Schumacher, Fredrick R, Berndt, Sonja I, Benlloch, Sara, Ahmed, Mahbubl, Goh, Chee, Sheng, Xin, Zhang, Zhuo, Muir, Kenneth, Govindasami, Koveela, Lophatananon, Artitaya, Stevens, Victoria L, Gapstur, Susan M, Carter, Brian D, Tangen, Catherine M, Goodman, Phyllis, Thompson, Ian M, Batra, Jyotsna, Chambers, Suzanne, Moya, Leire, Clements, Judith, Horvath, Lisa, Tilley, Wayne, Risbridger, Gail, Gronberg, Henrik, Aly, Markus, Nordström, Tobias, Pharoah, Paul, Pashayan, Nora, Schleutker, Johanna, Tammela, Teuvo LJ, Sipeky, Csilla, Auvinen, Anssi, Albanes, Demetrius, Weinstein, Stephanie, Wolk, Alicja, Hakansson, Niclas, West, Catharine, Dunning, Alison M, Burnet, Neil, Mucci, Lorelei, Giovannucci, Edward, Andriole, Gerald, Cussenot, Olivier, Cancel-Tassin, Géraldine, Koutros, Stella, Freeman, Laura E Beane, Sorensen, Karina Dalsgaard, Orntoft, Torben Falck, Borre, Michael, Maehle, Lovise, Grindedal, Eli Marie, Neal, David E, Donovan, Jenny L, Hamdy, Freddie C, Martin, Richard M, Travis, Ruth C, Key, Tim J, Hamilton, Robert J, Fleshner, Neil E, Finelli, Antonio, Ingles, Sue Ann, Stern, Mariana C, Rosenstein, Barry, Kerns, Sarah, Ostrer, Harry, Lu, Yong-Jie, Zhang, Hong-Wei, Feng, Ninghan, Mao, Xueying, Guo, Xin, Wang, Guomin, Sun, Zan, Giles, Graham G, Southey, Melissa C, MacInnis, Robert J, FitzGerald, Liesel M, Kibel, Adam S, Drake, Bettina F, Vega, Ana, Gómez-Caamaño, Antonio, Fachal, Laura, Szulkin, Robert, Eklund, Martin, Kogevinas, Manolis, Llorca, Javier, Castaño-Vinyals, Gemma, Penney, Kathryn L, Stampfer, Meir, Park, Jong Y, and Sellers, Thomas A
Subjects: Genetics, Aging, Urologic Diseases, Prostate Cancer, Prevention, Human Genome, Cancer, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Algorithms, Bayes Theorem, Black People, Chromosome Mapping, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Molecular Sequence Annotation, Multivariate Analysis, Polymorphism, Single Nucleotide, Prostatic Neoplasms, Quantitative Trait Loci, Risk, White People, PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium
Abstract: Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling.
Published: 2018

3. A meta-analysis of genome-wide association studies to identify prostate cancer susceptibility loci associated with aggressive and non-aggressive disease

Author: Amin Al Olama, Ali, Kote-Jarai, Zsofia, Schumacher, Fredrick R., Wiklund, Fredrik, Berndt, Sonja I., Benlloch, Sara, Giles, Graham G., Severi, Gianluca, Neal, David E., Hamdy, Freddie C., Donovan, Jenny L., Hunter, David J., Henderson, Brian E., Thun, Michael J., Gaziano, Michael, Giovannucci, Edward L., Siddiq, Afshan, Travis, Ruth C., Cox, David G., Canzian, Federico, Riboli, Elio, Key, Timothy J., Andriole, Gerald, Albanes, Demetrius, Hayes, Richard B., Schleutker, Johanna, Auvinen, Anssi, Tammela, Teuvo L.J., Weischer, Maren, Stanford, Janet L., Ostrander, Elaine A., Cybulski, Cezary, Lubinski, Jan, Thibodeau, Stephen N., Schaid, Daniel J., Sorensen, Karina D., Batra, Jyotsna, Clements, Judith A., Chambers, Suzanne, Aitken, Joanne, Gardiner, Robert A., Maier, Christiane, Vogel, Walther, Dörk, Thilo, Brenner, Hermann, Habuchi, Tomonori, Ingles, Sue, John, Esther M., Dickinson, Joanne L., Cannon-Albright, Lisa, Teixeira, Manuel R., Kaneva, Radka, Zhang, Hong-Wei, Lu, Yong-Jie, Park, Jong Y., Cooney, Kathleen A., Muir, Kenneth R., Leongamornlert, Daniel A., Saunders, Edward, Tymrakiewicz, Malgorzata, Mahmud, Nadiya, Guy, Michelle, Govindasami, Koveela, OʼBrien, Lynne T., Wilkinson, Rosemary A., Hall, Amanda L., Sawyer, Emma J., Dadaev, Tokhir, Morrison, Jonathan, Dearnaley, David P., Horwich, Alan, Huddart, Robert A., Khoo, Vincent S., Parker, Christopher C., Van As, Nicholas, Woodhouse, Christopher J., Thompson, Alan, Dudderidge, Tim, Ogden, Chris, Cooper, Colin S., Lophatonanon, Artitaya, Southey, Melissa C., Hopper, John L., English, Dallas, Virtamo, Jarmo, Le Marchand, Loic, Campa, Daniele, Kaaks, Rudolf, Lindstrom, Sara, Diver, W. Ryan, Gapstur, Susan, Yeager, Meredith, Cox, Angela, Stern, Mariana C., Corral, Roman, Aly, Markus, Isaacs, William, Adolfsson, Jan, Xu, Jianfeng, Zheng, S. Lilly, Wahlfors, Tiina, Taari, Kimmo, Kujala, Paula, Klarskov, Peter, Nordestgaard, Børge G., Røder, M. Andreas, Frikke-Schmidt, Ruth, Bojesen, Stig E., FitzGerald, Liesel M., Kolb, Suzanne, Kwon, Erika M., Karyadi, Danielle M., Orntoft, Torben Falck, Borre, Michael, Rinckleb, Antje, Luedeke, Manuel, Herkommer, Kathleen, Meyer, Andreas, Serth, Jürgen, Marthick, James R., Patterson, Briony, Wokolorczyk, Dominika, Spurdle, Amanda, Lose, Felicity, McDonnell, Shannon K., Joshi, Amit D., Shahabi, Ahva, Pinto, Pedro, Santos, Joana, Ray, Ana, Sellers, Thomas A., Lin, Hui-Yi, Stephenson, Robert A., Teerlink, Craig, Muller, Heiko, Rothenbacher, Dietrich, Tsuchiya, Norihiko, Narita, Shintaro, Cao, Guang-Wen, Slavov, Chavdar, Mitev, Vanio, Chanock, Stephen, Gronberg, Henrik, Haiman, Christopher A., Kraft, Peter, Easton, Douglas F., and Eeles, Rosalind A.
Published: 2013
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4. Germline variation at 8q24 and prostate cancer risk in men of European ancestry (vol 9, 4616, 2018)

Author: Matejcic, Marco, Saunders, Edward J., Dadaev, Tokhir, Brook, Mark N., Wang, Kan, Sheng, Xin, Al Olama, Ali Amin, Schumacher, Fredrick R., Ingles, Sue A., Govindasami, Koveela, Benlloch, Sara, Berndt, Sonja I., Albanes, Demetrius, Koutros, Stella, Muir, Kenneth, Stevens, Victoria L., Gapstur, Susan M., Tangen, Catherine M., Batra, Jyotsna, Clements, Judith, Gronberg, Henrik, Pashayan, Nora, Schleutker, Johanna, Wolk, Alicja, West, Catharine, Mucci, Lorelei, Kraft, Peter, Cancel-Tassin, Geraldine, Sorensen, Karina D., Maehle, Lovise, Grindedal, Eli M., Strom, Sara S., Neal, David E., Hamdy, Freddie C., Donovan, Jenny L., Travis, Ruth C., Hamilton, Robert J., Rosenstein, Barry, Lu, Yong-Jie, Giles, Graham G., Kibel, Adam S., Vega, Ana, Bensen, Jeanette T., Kogevinas, Manolis, Penney, Kathryn L., Park, Jong Y., Stanford, Janet L., Cybulski, Cezary, Nordestgaard, Borge G., Brenner, Hermann, Maier, Christiane, Kim, Jeri, Teixeira, Manuel R., Neuhausen, Susan L., De Ruyck, Kim, Razack, Azad, Newcomb, Lisa F., Lessel, Davor, Kaneva, Radka, Usmani, Nawaid, Claessens, Frank, Townsend, Paul A., Gago-Dominguez, Manuela, Roobol, Monique J., Menegaux, Florence, Khaw, Kay-Tee, Cannon-Albright, Lisa A., Pandha, Hardev, Thibodeau, Stephen N., Schaid, Daniel J., Wiklund, Fredrik, Chanock, Stephen J., Easton, Douglas F., Eeles, Rosalind A., Kote-Jarai, Zsofia, Conti, David V., Haiman, Christopher A., Henderson, Brian E., Stern, Mariana C., Thwaites, Alison, Guy, Michelle, Whitmore, Ian, Morgan, Angela, Fisher, Cyril, Hazel, Steve, Livni, Naomi, Cook, Margaret, Fachal, Laura, Weinstein, Stephanie, Freeman, Laura E. Beane, Hoover, Robert N., Machiela, Mitchell J., Lophatananon, Artitaya, Carter, Brian D., Goodman, Phyllis, Moya, Leire, Srinivasan, Srilakshmi, Kedda, Mary-Anne, Yeadon, Trina, Eckert, Allison, Eklund, Martin, Cavalli-Bjoerkman, Carin, Dunning, Alison M., Sipeky, Csilla, Hakansson, Niclas, Elliott, Rebecca, Ranu, Hardeep, Giovannucci, Edward, Turman, Constance, Hunter, David J., Cussenot, Olivier, Orntoft, Torben Falck, Lane, Athene, Lewis, Sarah J., Davis, Michael, Key, Tim J., Brown, Paul, Kulkarni, Girish S., Zlotta, Alexandre R., Fleshner, Neil E., Finelli, Antonio, Mao, Xueying, Marzec, Jacek, MacInnis, Robert J., Milne, Roger, Hopper, John L., Aguado, Miguel, Bustamante, Mariona, Castano-Vinyals, Gemma, Gracia-Lavedan, Esther, Cecchini, Lluis, Stampfer, Meir, Ma, Jing, Sellers, Thomas A., Geybels, Milan S., Park, Hyun, Zachariah, Babu, Kolb, Suzanne, Wokolorczyk, Dominika, Lubinski, Jan, Kluzniak, Wojciech, Nielsen, Sune F., Weisher, Maren, Cuk, Katarina, Vogel, Walther, Luedeke, Manuel, Logothetis, Christopher J., Paulo, Paula, Cardoso, Marta, Maia, Sofia, Silva, Maria P., Steele, Linda, Ding, Yuan Chun, De Meerleer, Gert, De Langhe, Sofie, Thierens, Hubert, Lim, Jasmine, Tan, Meng H., Ong, Aik T., Lin, Daniel W., Kachakova, Darina, Mitkova, Atanaska, Mitev, Vanio, Parliament, Matthew, Jenster, Guido, Bangma, Christopher, Schroder, F. H., Truong, Therese, Koudou, Yves Akoli, Michael, Agnieszka, Kierzek, Andrzej, Karlsson, Ami, Broms, Michael, Wu, Huihai, Aukim-Hastie, Claire, Tillmans, Lori, Riska, Shaun, McDonnell, Shannon K., Dearnaley, David, Spurdle, Amanda, Gardiner, Robert, Hayes, Vanessa, Butler, Lisa, Taylor, Renea, Papargiris, Melissa, Saunders, Pamela, Kujala, Paula, Talala, Kirsi, Taari, Kimmo, Bentzen, Soren, Hicks, Belynda, Vogt, Aurelie, Hutchinson, Amy, Cox, Angela, George, Anne, Toi, Ants, Evans, Andrew, van der Kwast, Theodorus H., Imai, Takashi, Saito, Shiro, Zhao, Shan-Chao, Ren, Guoping, Zhang, Yangling, Yu, Yongwei, Wu, Yudong, Wu, Ji, Zhou, Bo, Pedersen, John, Lobato-Busto, Ramon, Manuel Ruiz-Dominguez, Jose, Mengual, Lourdes, Alcaraz, Antonio, Pow-Sang, Julio, Herkommer, Kathleen, Vlahova, Aleksandrina, Dikov, Tihomir, Christova, Svetlana, Carracedo, Angel, Tretarre, Brigitte, Rebillard, Xavier, Mulot, Claire, Adolfsson, Jan, Stattin, Pär, Johansson, Jan-Erik, Martin, Richard M., Thompson, Ian M., Jr., Chambers, Suzanne, Aitken, Joanne, Horvath, Lisa, Haynes, Anne-Maree, Tilley, Wayne, Risbridger, Gail, Aly, Markus, Nordstrom, Tobias, Pharoah, Paul, Tammela, Teuvo L. J., Murtola, Teemu, Auvinen, Anssi, Burnet, Neil, Barnett, Gill, Andriole, Gerald, Klim, Aleksandra, Drake, Bettina F., Borre, Michael, Kerns, Sarah, Ostrer, Harry, Zhang, Hong-Wei, Cao, Guangwen, Lin, Ji, Ling, Jin, Li, Meiling, Feng, Ninghan, Li, Jie, He, Weiyang, Guo, Xin, Sun, Zan, Wang, Guomin, Guo, Jianming, Southey, Melissa C., FitzGerald, Liesel M., Marsden, Gemma, Gomez-Caamano, Antonio, Carballo, Ana, Peleteiro, Paula, Calvo, Patricia, Szulkin, Robert, Llorca, Javier, Dierssen-Sotos, Trinidad, Gomez-Acebo, Ines, Lin, Hui-Yi, Ostrander, Elaine A., Bisbjerg, Rasmus, Klarskov, Peter, Roder, Martin Andreas, Iversen, Peter, Holleczek, Bernd, Stegmaier, Christa, Schnoeller, Thomas, Bohnert, Philipp, John, Esther M., Ost, Piet, Teo, Soo-Hwang, Gamulin, Marija, Kulis, Tomislav, Kastelan, Zeljko, Slavov, Chavdar, Popov, Elenko, Van den Broeck, Thomas, Joniau, Steven, Larkin, Samantha, Esteban Castelao, Jose, Martinez, Maria Elena, van Schaik, Ron H. N., Xu, Jianfeng, Lindstrom, Sara, Riboli, Elio, Berry, Clare, Siddiq, Afshan, Canzian, Federico, Kolonel, Laurence N., Le Marchand, Loic, Freedman, Matthew, Cenee, Sylvie, Sanchez, Marie, Matejcic, Marco, Saunders, Edward J., Dadaev, Tokhir, Brook, Mark N., Wang, Kan, Sheng, Xin, Al Olama, Ali Amin, Schumacher, Fredrick R., Ingles, Sue A., Govindasami, Koveela, Benlloch, Sara, Berndt, Sonja I., Albanes, Demetrius, Koutros, Stella, Muir, Kenneth, Stevens, Victoria L., Gapstur, Susan M., Tangen, Catherine M., Batra, Jyotsna, Clements, Judith, Gronberg, Henrik, Pashayan, Nora, Schleutker, Johanna, Wolk, Alicja, West, Catharine, Mucci, Lorelei, Kraft, Peter, Cancel-Tassin, Geraldine, Sorensen, Karina D., Maehle, Lovise, Grindedal, Eli M., Strom, Sara S., Neal, David E., Hamdy, Freddie C., Donovan, Jenny L., Travis, Ruth C., Hamilton, Robert J., Rosenstein, Barry, Lu, Yong-Jie, Giles, Graham G., Kibel, Adam S., Vega, Ana, Bensen, Jeanette T., Kogevinas, Manolis, Penney, Kathryn L., Park, Jong Y., Stanford, Janet L., Cybulski, Cezary, Nordestgaard, Borge G., Brenner, Hermann, Maier, Christiane, Kim, Jeri, Teixeira, Manuel R., Neuhausen, Susan L., De Ruyck, Kim, Razack, Azad, Newcomb, Lisa F., Lessel, Davor, Kaneva, Radka, Usmani, Nawaid, Claessens, Frank, Townsend, Paul A., Gago-Dominguez, Manuela, Roobol, Monique J., Menegaux, Florence, Khaw, Kay-Tee, Cannon-Albright, Lisa A., Pandha, Hardev, Thibodeau, Stephen N., Schaid, Daniel J., Wiklund, Fredrik, Chanock, Stephen J., Easton, Douglas F., Eeles, Rosalind A., Kote-Jarai, Zsofia, Conti, David V., Haiman, Christopher A., Henderson, Brian E., Stern, Mariana C., Thwaites, Alison, Guy, Michelle, Whitmore, Ian, Morgan, Angela, Fisher, Cyril, Hazel, Steve, Livni, Naomi, Cook, Margaret, Fachal, Laura, Weinstein, Stephanie, Freeman, Laura E. Beane, Hoover, Robert N., Machiela, Mitchell J., Lophatananon, Artitaya, Carter, Brian D., Goodman, Phyllis, Moya, Leire, Srinivasan, Srilakshmi, Kedda, Mary-Anne, Yeadon, Trina, Eckert, Allison, Eklund, Martin, Cavalli-Bjoerkman, Carin, Dunning, Alison M., Sipeky, Csilla, Hakansson, Niclas, Elliott, Rebecca, Ranu, Hardeep, Giovannucci, Edward, Turman, Constance, Hunter, David J., Cussenot, Olivier, Orntoft, Torben Falck, Lane, Athene, Lewis, Sarah J., Davis, Michael, Key, Tim J., Brown, Paul, Kulkarni, Girish S., Zlotta, Alexandre R., Fleshner, Neil E., Finelli, Antonio, Mao, Xueying, Marzec, Jacek, MacInnis, Robert J., Milne, Roger, Hopper, John L., Aguado, Miguel, Bustamante, Mariona, Castano-Vinyals, Gemma, Gracia-Lavedan, Esther, Cecchini, Lluis, Stampfer, Meir, Ma, Jing, Sellers, Thomas A., Geybels, Milan S., Park, Hyun, Zachariah, Babu, Kolb, Suzanne, Wokolorczyk, Dominika, Lubinski, Jan, Kluzniak, Wojciech, Nielsen, Sune F., Weisher, Maren, Cuk, Katarina, Vogel, Walther, Luedeke, Manuel, Logothetis, Christopher J., Paulo, Paula, Cardoso, Marta, Maia, Sofia, Silva, Maria P., Steele, Linda, Ding, Yuan Chun, De Meerleer, Gert, De Langhe, Sofie, Thierens, Hubert, Lim, Jasmine, Tan, Meng H., Ong, Aik T., Lin, Daniel W., Kachakova, Darina, Mitkova, Atanaska, Mitev, Vanio, Parliament, Matthew, Jenster, Guido, Bangma, Christopher, Schroder, F. H., Truong, Therese, Koudou, Yves Akoli, Michael, Agnieszka, Kierzek, Andrzej, Karlsson, Ami, Broms, Michael, Wu, Huihai, Aukim-Hastie, Claire, Tillmans, Lori, Riska, Shaun, McDonnell, Shannon K., Dearnaley, David, Spurdle, Amanda, Gardiner, Robert, Hayes, Vanessa, Butler, Lisa, Taylor, Renea, Papargiris, Melissa, Saunders, Pamela, Kujala, Paula, Talala, Kirsi, Taari, Kimmo, Bentzen, Soren, Hicks, Belynda, Vogt, Aurelie, Hutchinson, Amy, Cox, Angela, George, Anne, Toi, Ants, Evans, Andrew, van der Kwast, Theodorus H., Imai, Takashi, Saito, Shiro, Zhao, Shan-Chao, Ren, Guoping, Zhang, Yangling, Yu, Yongwei, Wu, Yudong, Wu, Ji, Zhou, Bo, Pedersen, John, Lobato-Busto, Ramon, Manuel Ruiz-Dominguez, Jose, Mengual, Lourdes, Alcaraz, Antonio, Pow-Sang, Julio, Herkommer, Kathleen, Vlahova, Aleksandrina, Dikov, Tihomir, Christova, Svetlana, Carracedo, Angel, Tretarre, Brigitte, Rebillard, Xavier, Mulot, Claire, Adolfsson, Jan, Stattin, Pär, Johansson, Jan-Erik, Martin, Richard M., Thompson, Ian M., Jr., Chambers, Suzanne, Aitken, Joanne, Horvath, Lisa, Haynes, Anne-Maree, Tilley, Wayne, Risbridger, Gail, Aly, Markus, Nordstrom, Tobias, Pharoah, Paul, Tammela, Teuvo L. J., Murtola, Teemu, Auvinen, Anssi, Burnet, Neil, Barnett, Gill, Andriole, Gerald, Klim, Aleksandra, Drake, Bettina F., Borre, Michael, Kerns, Sarah, Ostrer, Harry, Zhang, Hong-Wei, Cao, Guangwen, Lin, Ji, Ling, Jin, Li, Meiling, Feng, Ninghan, Li, Jie, He, Weiyang, Guo, Xin, Sun, Zan, Wang, Guomin, Guo, Jianming, Southey, Melissa C., FitzGerald, Liesel M., Marsden, Gemma, Gomez-Caamano, Antonio, Carballo, Ana, Peleteiro, Paula, Calvo, Patricia, Szulkin, Robert, Llorca, Javier, Dierssen-Sotos, Trinidad, Gomez-Acebo, Ines, Lin, Hui-Yi, Ostrander, Elaine A., Bisbjerg, Rasmus, Klarskov, Peter, Roder, Martin Andreas, Iversen, Peter, Holleczek, Bernd, Stegmaier, Christa, Schnoeller, Thomas, Bohnert, Philipp, John, Esther M., Ost, Piet, Teo, Soo-Hwang, Gamulin, Marija, Kulis, Tomislav, Kastelan, Zeljko, Slavov, Chavdar, Popov, Elenko, Van den Broeck, Thomas, Joniau, Steven, Larkin, Samantha, Esteban Castelao, Jose, Martinez, Maria Elena, van Schaik, Ron H. N., Xu, Jianfeng, Lindstrom, Sara, Riboli, Elio, Berry, Clare, Siddiq, Afshan, Canzian, Federico, Kolonel, Laurence N., Le Marchand, Loic, Freedman, Matthew, Cenee, Sylvie, and Sanchez, Marie
Abstract: Correction to: Nature Communications; https://doi.org/10.1038/s41467-018-06863-1, published online 5 November 2018.
Published: 2019
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5. Germline variation at 8q24 and prostate cancer risk in men of European ancestry

Author: Matejcic, Marco, Saunders, Edward J., Dadaev, Tokhir, Brook, Mark N., Wang, Kan, Sheng, Xin, Olama, Ali Amin Al, Schumacher, Fredrick R., Ingles, Sue A., Govindasami, Koveela, Benlloch, Sara, Berndt, Sonja I., Albanes, Demetrius, Koutros, Stella, Muir, Kenneth, Stevens, Victoria L., Gapstur, Susan M., Tangen, Catherine M., Batra, Jyotsna, Clements, Judith, Grönberg, Henrik, Pashayan, Nora, Schleutker, Johanna, Wolk, Alicja, West, Catharine, Mucci, Lorelei, Kraft, Peter, Cancel-Tassin, Géraldine, Sorensen, Karina D., Maehle, Lovise, Grindedal, Eli M., Strom, Sara S., Neal, David E., Hamdy, Freddie C., Donovan, Jenny L., Travis, Ruth C., Hamilton, Robert J., Rosenstein, Barry, Lu, Yong-Jie, Giles, Graham G., Kibel, Adam S., Vega, Ana, Bensen, Jeanette T., Kogevinas, Manolis, Penney, Kathryn L., Park, Jong Y., Stanford, Janet L., Cybulski, Cezary, Nordestgaard, Børge G., Brenner, Hermann, Maier, Christiane, Kim, Jeri, Teixeira, Manuel R., Neuhausen, Susan L., De Ruyck, Kim, Razack, Azad, Newcomb, Lisa F., Lessel, Davor, Kaneva, Radka, Usmani, Nawaid, Claessens, Frank, Townsend, Paul A., Gago-Dominguez, Manuela, Roobol, Monique J., Menegaux, Florence, Khaw, Kay-Tee, Cannon-Albright, Lisa A., Pandha, Hardev, Thibodeau, Stephen N., Schaid, Daniel J., Henderson, Brian E., Stern, Mariana C., Thwaites, Alison, Guy, Michelle, Whitmore, Ian, Morgan, Angela, Fisher, Cyril, Hazel, Steve, Livni, Naomi, Cook, Margaret, Fachal, Laura, Weinstein, Stephanie, Beane Freeman, Laura E., Hoover, Robert N., Machiela, Mitchell J., Lophatananon, Artitaya, Carter, Brian D., Goodman, Phyllis J., Moya, Leire, Srinivasan, Srilakshmi, Kedda, Mary-Anne, Yeadon, Trina, Eckert, Allison, Eklund, Martin, Cavalli-Bjoerkman, Carin, Dunning, Alison M., Sipeky, Csilla, Hakansson, Niclas, Elliott, Rebecca, Ranu, Hardeep, Giovannucci, Edward, Turman, Constance, Hunter, David J., Cussenot, Olivier, Orntoft, Torben Falck, Lane, Athene, Lewis, Sarah J., Davis, Michael, Key, Tim J., Brown, Paul, Kulkarni, Girish S., Zlotta, Alexandre R., Fleshner, Neil E., Finelli, Antonio, Mao, Xueying, Marzec, Jacek, MacInnis, Robert J., Milne, Roger, Hopper, John L., Aguado, Miguel, Bustamante, Mariona, Castaño-Vinyals, Gemma, Gracia-Lavedan, Esther, Cecchini, Lluís, Stampfer, Meir, Ma, Jing, Sellers, Thomas A., Geybels, Milan S., Park, Hyun, Zachariah, Babu, Kolb, Suzanne, Wokolorczyk, Dominika, Lubinski, Jan, Kluzniak, Wojciech, Nielsen, Sune F., Weisher, Maren, Cuk, Katarina, Vogel, Walther, Luedeke, Manuel, Logothetis, Christopher J. J., Paulo, Paula, Cardoso, Marta, Maia, Sofia, Silva, Maria P., Steele, Linda, Ding, Yuan Chun, De Meerleer, Gert, De Langhe, Sofie, Thierens, Hubert, Lim, Jasmine, Tan, Meng H., Ong, Aik T., Lin, Daniel W., Kachakova, Darina, Mitkova, Atanaska, Mitev, Vanio, Parliament, Matthew, Jenster, Guido, Bangma, Christopher, Schroder, F. H., Truong, Thérèse, Koudou, Yves Akoli, Michael, Agnieszka, Kierzek, Andrzej, Karlsson, Ami, Broms, Michael, Wu, Huihai, Aukim-Hastie, Claire, Tillmans, Lori, Riska, Shaun, McDonnell, Shannon K., Dearnaley, David, Spurdle, Amanda, Gardiner, Robert, Hayes, Vanessa, Butler, Lisa, Taylor, Renea, Papargiris, Melissa, Saunders, Pamela, Kujala, Paula, Talala, Kirsi, Taari, Kimmo, Bentzen, Søren, Hicks, Belynda, Vogt, Aurelie, Hutchinson, Amy, Cox, Angela, George, Anne, Toi, Ants, Evans, Andrew, van der Kwast, Theodorus H., Imai, Takashi, Saito, Shiro, Zhao, Shan-Chao, Ren, Guoping, Zhang, Yangling, Yu, Yongwei, Wu, Yudong, Wu, Ji, Zhou, Bo, Pedersen, John, Lobato-Busto, Ramón, Ruiz-Dominguez, José Manuel, Mengual, Lourdes, Alcaraz, Antonio, Pow-Sang, Julio, Herkommer, Kathleen, Vlahova, Aleksandrina, Dikov, Tihomir, Christova, Svetlana, Carracedo, Angel, Tretarre, Brigitte, Rebillard, Xavier, Mulot, Claire, Adolfsson, Jan, Stattin, Par, Johansson, Jan-Erik, Martin, Richard M., Thompson, Ian M., Chambers, Suzanne, Aitken, Joanne, Horvath, Lisa, Haynes, Anne-Maree, Tilley, Wayne, Risbridger, Gail, Aly, Markus, Nordström, Tobias, Pharoah, Paul, Tammela, Teuvo L. J., Murtola, Teemu, Auvinen, Anssi, Burnet, Neil, Barnett, Gill, Andriole, Gerald, Klim, Aleksandra, Drake, Bettina F., Borre, Michael, Kerns, Sarah, Ostrer, Harry, Zhang, Hong-Wei, Cao, Guangwen, Lin, Ji, Ling, Jin, Li, Meiling, Feng, Ninghan, Li, Jie, He, Weiyang, Guo, Xin, Sun, Zan, Wang, Guomin, Guo, Jianming, Southey, Melissa C., Fitzgerald, Liesel M., Marsden, Gemma, Gómez-Caamaño, Antonio, Carballo, Ana, Peleteiro, Paula, Calvo, Patricia, Szulkin, Robert, Llorca, Javier, Dierssen-Sotos, Trinidad, Gómez Acebo, Inés, Lin, Hui-Yi, Ostrander, Elaine A., Bisbjerg, Rasmus, Klarskov, Peter, Røder, Martin Andreas, Iversen, Peter, Holleczek, Bernd, Stegmaier, Christa, Schnoeller, Thomas, Bohnert, Philipp, John, Esther M., Ost, Piet, Teo, Soo-Hwang, Gamulin, Marija, Kulis, Tomislav, Kastelan, Zeljko, Slavov, Chavdar, Popov, Elenko, Van den Broeck, Thomas, Joniau, Steven, Larkin, Samantha, Castelao, Jose Esteban, Martinez, Maria Elena, van Schaik, Ron H. N., Xu, Jianfeng, Lindström, Sara, Riboli, Elio, Berry, Clare, Siddiq, Afshan, Canzian, Federico, Kolonel, Laurence N., Le Marchand, Loic, Freedman, Matthew, Cenee, Sylvie, Sanchez, Marie, Wiklund, Fredrik, Chanock, Stephen J., Easton, Douglas F., Eeles, Rosalind A., Kote-Jarai, Zsofia, Conti, David V., Haiman, Christopher A., Universidad de Cantabria, De Meerleer, Gert, Keck School of Medicine [Los Angeles], University of Southern California (USC), The institute of cancer research [London], Department of Clinical Neurosciences [Cambridge], University of Cambridge [UK] (CAM), Centre for Cancer Genetic Epidemiology [Cambridge], Department of Oncology-University of Cambridge [UK] (CAM), Case Western Reserve University [Cleveland], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Warwick Medical School, University of Warwick [Coventry], University of Manchester [Manchester], Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology [Brisbane] (QUT), Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], University College of London [London] (UCL), University of Turku, University of Tampere [Finland], The Institute of Environmental Medicine [Stockholm] (IMM), Manchester Academic Health Science Centre (MAHSC), Harvard School of Public Health, Harvard T.H. Chan School of Public Health, Université Pierre et Marie Curie - Paris 6 (UPMC), Aarhus University Hospital, Aarhus University [Aarhus], Oslo University Hospital [Oslo], The University of Texas M.D. Anderson Cancer Center [Houston], Addenbrooke's Hospital, Cambridge University NHS Trust, University of Oxford [Oxford], School of Social and Community Medicine [Bristol], University of Bristol [Bristol], Icahn School of Medicine at Mount Sinai [New York] (MSSM), Centre for Molecular Oncology and Imaging, Centre for Molecular Oncology and Imaging, Barts Cancer Institute, Queen Mary University of London (QMUL), University of Melbourne, Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), CIBER de Enfermedades Raras (CIBERER), Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, CIBER de Epidemiología y Salud Pública (CIBERESP), IMIM-Hospital del Mar, Generalitat de Catalunya, Universitat Pompeu Fabra [Barcelona] (UPF), University of Washington [Seattle], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), National Center for Tumor Diseases [Dresden] (NCT), Technische Universität Dresden = Dresden University of Technology (TU Dresden)-German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ)-Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Universität Ulm - Ulm University [Ulm, Allemagne], Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto, Universiteit Gent = Ghent University [Belgium] (UGENT), University of Malaya [Kuala Lumpur, Malaisie], Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), University of Alberta, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of California [San Diego] (UC San Diego), University of California, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Paris-Saclay, University of Utah School of Medicine [Salt Lake City], University of Surrey (UNIS), Mayo Clinic [Rochester], Royal Marsden NHS Foundation Trust, Dadaev, Tokhir [0000-0002-8268-0438], Brook, Mark N [0000-0002-8969-2378], Wang, Kan [0000-0002-0640-6058], Olama, Ali Amin Al [0000-0002-7178-3431], Schumacher, Fredrick R [0000-0002-3073-7463], Muir, Kenneth [0000-0001-6429-988X], Batra, Jyotsna [0000-0003-4646-6247], Pashayan, Nora [0000-0003-0843-2468], Schleutker, Johanna [0000-0002-1863-0305], Wolk, Alicja [0000-0001-7387-6845], Cancel-Tassin, Géraldine [0000-0002-9583-6382], Sorensen, Karina D [0000-0002-4902-5490], Lessel, Davor [0000-0003-4496-244X], Roobol, Monique J [0000-0001-6967-1708], Chanock, Stephen J [0000-0002-2324-3393], Easton, Douglas F [0000-0003-2444-3247], Eeles, Rosalind A [0000-0002-3698-6241], Apollo - University of Cambridge Repository, University of Cambridge [UK] (CAM)-Department of Oncology, University of Oxford, Universidade do Porto = University of Porto, Universiteit Gent = Ghent University (UGENT), University of Malaya = Universiti Malaya [Kuala Lumpur, Malaisie] (UM), University of California (UC), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Gestionnaire, Hal Sorbonne Université, Urology, University Management, Clinicum, and HUS Abdominal Center
Subjects: 0301 basic medicine, Oncology, Male, [SDV]Life Sciences [q-bio], LOCI, General Physics and Astronomy, Genome-wide association study, PROGRESSION, [SDV.GEN] Life Sciences [q-bio]/Genetics, MYC, SUSCEPTIBILITY, UP-REGULATION, Prostate cancer, Risk Factors, Genotype, Urologi och njurmedicin, Medicine, lcsh:Science, Pròstata -- Càncer, education.field_of_study, RARE VARIANT, Multidisciplinary, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Manchester Cancer Research Centre, LONG NONCODING RNA, Chromosome Mapping, Men, 3. Good health, [SDV] Life Sciences [q-bio], Multidisciplinary Sciences, Science & Technology - Other Topics, Disease Susceptibility, Risk assessment, Chromosomes, Human, Pair 8, Genetic Markers, medicine.medical_specialty, Science, 3122 Cancers, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Risk Assessment, Article, General Biochemistry, Genetics and Molecular Biology, White People, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, SDG 3 - Good Health and Well-being, Internal medicine, Genetics, Urology and Nephrology, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, education, Author Correction, METAANALYSIS, [SDV.GEN]Life Sciences [q-bio]/Genetics, Cancer och onkologi, Science & Technology, Càncer de pròstata, business.industry, ResearchInstitutes_Networks_Beacons/mcrc, Case-control study, Cancer, Prostatic Neoplasms, General Chemistry, 3126 Surgery, anesthesiology, intensive care, radiology, medicine.disease, 030104 developmental biology, Homes, Haplotypes, Cancer and Oncology, Case-Control Studies, lcsh:Q, Population Risk, business, Genètica, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p, Chromosome 8q24 is known to be a major susceptibility region for prostate cancer risk. Here the authors analyze genetic data across the 8q24 region from 71,535 prostate cancer patients identifying 12 risk loci, three previously unreported, highlighting the contribution of germline variation at this locus.
Published: 2018

6. Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci

Author: Schumacher, Fredrick R., Al Olama, Ali Amin, Berndt, Sonja I., Benlloch, Sara, Ahmed, Mahbubl, Saunders, Edward J., Dadaev, Tokhir, Leongamornlert, Daniel, Anokian, Ezequiel, Cieza-Borrella, Clara, Goh, Chee, Brook, Mark N., Sheng, Xin, Fachal, Laura, Dennis, Joe, Tyrer, Jonathan, Muir, Kenneth, Lophatananon, Artitaya, Stevens, Victoria L., Gapstur, Susan M., Carter, Brian D., Tangen, Catherine M., Goodman, Phyllis J., Thompson, Ian M., Jr., Batra, Jyotsna, Chambers, Suzanne, Moya, Leire, Clements, Judith, Horvath, Lisa, Tilley, Wayne, Risbridger, Gail P., Gronberg, Henrik, Aly, Markus, Nordstrom, Tobias, Pharoah, Paul, Pashayan, Nora, Schleutker, Johanna, Tammela, Teuvo L. J., Sipeky, Csilla, Auvinen, Anssi, Albanes, Demetrius, Weinstein, Stephanie, Wolk, Alicja, Hakansson, Niclas, West, Catharine M. L., Dunning, Alison M., Burnet, Neil, Mucci, Lorelei A., Giovannucci, Edward, Andriole, Gerald L., Cussenot, Olivier, Cancel-Tassin, Geraldine, Koutros, Stella, Freeman, Laura E. Beane, Sorensen, Karina Dalsgaard, Orntoft, Torben Falck, Borre, Michael, Maehle, Lovise, Grindedal, Eli Marie, Neal, David E., Donovan, Jenny L., Hamdy, Freddie C., Martin, Richard M., Travis, Ruth C., Key, Tim J., Hamilton, Robert J., Fleshner, Neil E., Finelli, Antonio, Ingles, Sue Ann, Stern, Mariana C., Rosenstein, Barry S., Kerns, Sarah L., Ostrer, Harry, Lu, Yong-Jie, Zhang, Hong-Wei, Feng, Ninghan, Mao, Xueying, Guo, Xin, Wang, Guomin, Sun, Zan, Giles, Graham G., Southey, Melissa C., MacInnis, Robert J., FitzGerald, Liesel M., Kibel, Adam S., Drake, Bettina F., Vega, Ana, Gomez-Caamano, Antonio, Szulkin, Robert, Eklund, Martin, Kogevinas, Manolis, Llorca, Javier, Castano-Vinyals, Gemma, Penney, Kathryn L., Stampfer, Meir, Park, Jong Y., Sellers, Thomas A., Lin, Hui-Yi, Stanford, Janet L., Cybulski, Cezary, Wokolorczyk, Dominika, Lubinski, Jan, Ostrander, Elaine A., Geybels, Milan S., Nordestgaard, Borge G., Nielsen, Sune F., Weischer, Maren, Bisbjerg, Rasmus, Roder, Martin Andreas, Iversen, Peter, Brenner, Hermann, Cuk, Katarina, Holleczek, Bernd, Maier, Christiane, Luedeke, Manuel, Schnoeller, Thomas, Kim, Jeri, Logothetis, Christopher J., John, Esther M., Teixeira, Manuel R., Paulo, Paula, Cardoso, Marta, Neuhausen, Susan L., Steele, Linda, Ding, Yuan Chun, De Ruyck, Kim, De Meerleer, Gert, Ost, Piet, Razack, Azad, Lim, Jasmine, Teo, Soo-Hwang, Lin, Daniel W., Newcomb, Lisa F., Lessel, Davor, Gamulin, Marija, Kulis, Tomislav, Kaneva, Radka, Usmani, Nawaid, Singhal, Sandeep, Slavov, Chavdar, Mitev, Vanio, Parliament, Matthew, Claessens, Frank, Joniau, Steven, Van den Broeck, Thomas, Larkin, Samantha, Townsend, Paul A., Aukim-Hastie, Claire, Dominguez, Manuela Gago, Castelao, Jose Esteban, Martinez, Maria Elena, Roobol, Monique J., Jenster, Guido, van Schaik, Ron H. N., Menegaux, Florence, Truong, Therese, Koudou, Yves Akoli, Xu, Jianfeng, Khaw, Kay-Tee, Cannon-Albright, Lisa, Pandha, Hardev, Michael, Agnieszka, Thibodeau, Stephen N., McDonnell, Shannon K., Schaid, Daniel J., Lindstrom, Sara, Turman, Constance, Ma, Jing, Hunter, David J., Riboli, Elio, Siddiq, Afshan, Canzian, Federico, Kolonel, Laurence N., Le Marchand, Loic, Hoover, Robert N., Machiela, Mitchell J., Cui, Zuxi, Kraft, Peter, Conti, David V., Easton, Douglas F., Wiklund, Fredrik, Chanock, Stephen J., Henderson, Brian E., Kote-Jarai, Zsofia, Haiman, Christopher A., Eeles, Rosalind A., Schumacher, Fredrick R., Al Olama, Ali Amin, Berndt, Sonja I., Benlloch, Sara, Ahmed, Mahbubl, Saunders, Edward J., Dadaev, Tokhir, Leongamornlert, Daniel, Anokian, Ezequiel, Cieza-Borrella, Clara, Goh, Chee, Brook, Mark N., Sheng, Xin, Fachal, Laura, Dennis, Joe, Tyrer, Jonathan, Muir, Kenneth, Lophatananon, Artitaya, Stevens, Victoria L., Gapstur, Susan M., Carter, Brian D., Tangen, Catherine M., Goodman, Phyllis J., Thompson, Ian M., Jr., Batra, Jyotsna, Chambers, Suzanne, Moya, Leire, Clements, Judith, Horvath, Lisa, Tilley, Wayne, Risbridger, Gail P., Gronberg, Henrik, Aly, Markus, Nordstrom, Tobias, Pharoah, Paul, Pashayan, Nora, Schleutker, Johanna, Tammela, Teuvo L. J., Sipeky, Csilla, Auvinen, Anssi, Albanes, Demetrius, Weinstein, Stephanie, Wolk, Alicja, Hakansson, Niclas, West, Catharine M. L., Dunning, Alison M., Burnet, Neil, Mucci, Lorelei A., Giovannucci, Edward, Andriole, Gerald L., Cussenot, Olivier, Cancel-Tassin, Geraldine, Koutros, Stella, Freeman, Laura E. Beane, Sorensen, Karina Dalsgaard, Orntoft, Torben Falck, Borre, Michael, Maehle, Lovise, Grindedal, Eli Marie, Neal, David E., Donovan, Jenny L., Hamdy, Freddie C., Martin, Richard M., Travis, Ruth C., Key, Tim J., Hamilton, Robert J., Fleshner, Neil E., Finelli, Antonio, Ingles, Sue Ann, Stern, Mariana C., Rosenstein, Barry S., Kerns, Sarah L., Ostrer, Harry, Lu, Yong-Jie, Zhang, Hong-Wei, Feng, Ninghan, Mao, Xueying, Guo, Xin, Wang, Guomin, Sun, Zan, Giles, Graham G., Southey, Melissa C., MacInnis, Robert J., FitzGerald, Liesel M., Kibel, Adam S., Drake, Bettina F., Vega, Ana, Gomez-Caamano, Antonio, Szulkin, Robert, Eklund, Martin, Kogevinas, Manolis, Llorca, Javier, Castano-Vinyals, Gemma, Penney, Kathryn L., Stampfer, Meir, Park, Jong Y., Sellers, Thomas A., Lin, Hui-Yi, Stanford, Janet L., Cybulski, Cezary, Wokolorczyk, Dominika, Lubinski, Jan, Ostrander, Elaine A., Geybels, Milan S., Nordestgaard, Borge G., Nielsen, Sune F., Weischer, Maren, Bisbjerg, Rasmus, Roder, Martin Andreas, Iversen, Peter, Brenner, Hermann, Cuk, Katarina, Holleczek, Bernd, Maier, Christiane, Luedeke, Manuel, Schnoeller, Thomas, Kim, Jeri, Logothetis, Christopher J., John, Esther M., Teixeira, Manuel R., Paulo, Paula, Cardoso, Marta, Neuhausen, Susan L., Steele, Linda, Ding, Yuan Chun, De Ruyck, Kim, De Meerleer, Gert, Ost, Piet, Razack, Azad, Lim, Jasmine, Teo, Soo-Hwang, Lin, Daniel W., Newcomb, Lisa F., Lessel, Davor, Gamulin, Marija, Kulis, Tomislav, Kaneva, Radka, Usmani, Nawaid, Singhal, Sandeep, Slavov, Chavdar, Mitev, Vanio, Parliament, Matthew, Claessens, Frank, Joniau, Steven, Van den Broeck, Thomas, Larkin, Samantha, Townsend, Paul A., Aukim-Hastie, Claire, Dominguez, Manuela Gago, Castelao, Jose Esteban, Martinez, Maria Elena, Roobol, Monique J., Jenster, Guido, van Schaik, Ron H. N., Menegaux, Florence, Truong, Therese, Koudou, Yves Akoli, Xu, Jianfeng, Khaw, Kay-Tee, Cannon-Albright, Lisa, Pandha, Hardev, Michael, Agnieszka, Thibodeau, Stephen N., McDonnell, Shannon K., Schaid, Daniel J., Lindstrom, Sara, Turman, Constance, Ma, Jing, Hunter, David J., Riboli, Elio, Siddiq, Afshan, Canzian, Federico, Kolonel, Laurence N., Le Marchand, Loic, Hoover, Robert N., Machiela, Mitchell J., Cui, Zuxi, Kraft, Peter, Conti, David V., Easton, Douglas F., Wiklund, Fredrik, Chanock, Stephen J., Henderson, Brian E., Kote-Jarai, Zsofia, Haiman, Christopher A., and Eeles, Rosalind A.
Abstract: Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P < 5.0 x 10(-8)) with PrCa and one locus significantly associated with early-onset PrCa (<= 55 years). Our findings include missense variants rs1800057 (odds ratio (OR) = 1.16; P = 8.2 x 10(-9); G>C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 x 10(-9); T>G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55-2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04-6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa1.
Published: 2018
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7. epiG:statistical inference and profiling of DNA methylation from whole-genome bisulfite sequencing data

Author: Vincent, Martin, Mundbjerg, Kamilla, Pedersen, Jakob Skou, Liang, Gangning, Jones, Peter A., Orntoft, Torben Falck, Sorensen, Karina Dalsgaard, Wiuf, Carsten, Vincent, Martin, Mundbjerg, Kamilla, Pedersen, Jakob Skou, Liang, Gangning, Jones, Peter A., Orntoft, Torben Falck, Sorensen, Karina Dalsgaard, and Wiuf, Carsten
Published: 2017

8. Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma

Author: Hedegaard, Jakob, Lamy, Philippe, Nordentoft, Iver, Algaba, Ferran, Hoyer, Soren, Ulhoi, Benedicte Parm, Vang, Soren, Reinert, Thomas, Hermann, Gregers G., Mogensen, Karin, Thomsen, Mathilde Borg Houlberg, Nielsen, Morten Muhlig, Marquez, Mirari, Segersten, Ulrika, Aine, Mattias, Hoglund, Mattias, Birkenkamp-Demtroder, Karin, Fristrup, Niels, Borre, Michael, Hartmann, Arndt, Stoehr, Robert, Wach, Sven, Keck, Bastian, Seitz, Anna Katharina, Nawroth, Roman, Maurer, Tobias, Tulic, Cane, Simic, Tatjana, Junker, Kerstin, Horstmann, Marcus, Harving, Niels, Petersen, Astrid Christine, Luz Calle, M., Steyerberg, Ewout W., Beukers, Willemien, van Kessel, Kim E. M., Jensen, Jorgen Bjerggaard, Pedersen, Jakob Skou, Malmström, Per-Uno, Malats, Nuria, Real, Francisco X., Zwarthoff, Ellen C., Orntoft, Torben Falck, Dyrskjot, Lars, Hedegaard, Jakob, Lamy, Philippe, Nordentoft, Iver, Algaba, Ferran, Hoyer, Soren, Ulhoi, Benedicte Parm, Vang, Soren, Reinert, Thomas, Hermann, Gregers G., Mogensen, Karin, Thomsen, Mathilde Borg Houlberg, Nielsen, Morten Muhlig, Marquez, Mirari, Segersten, Ulrika, Aine, Mattias, Hoglund, Mattias, Birkenkamp-Demtroder, Karin, Fristrup, Niels, Borre, Michael, Hartmann, Arndt, Stoehr, Robert, Wach, Sven, Keck, Bastian, Seitz, Anna Katharina, Nawroth, Roman, Maurer, Tobias, Tulic, Cane, Simic, Tatjana, Junker, Kerstin, Horstmann, Marcus, Harving, Niels, Petersen, Astrid Christine, Luz Calle, M., Steyerberg, Ewout W., Beukers, Willemien, van Kessel, Kim E. M., Jensen, Jorgen Bjerggaard, Pedersen, Jakob Skou, Malmström, Per-Uno, Malats, Nuria, Real, Francisco X., Zwarthoff, Ellen C., Orntoft, Torben Falck, and Dyrskjot, Lars
Abstract: Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease with widely different outcomes. We performed a comprehensive transcriptional analysis of 460 early-stage urothelial carcinomas and showed that NMIBC can be subgrouped into three major classes with basal-and luminal-like characteristics and different clinical outcomes. Large differences in biological processes such as the cell cycle, epithelial-mesenchymal transition, and differentiation were observed. Analysis of transcript variants revealed frequent mutations in genes encoding proteins involved in chromatin organization and cytoskeletal functions. Furthermore, mutations in well-known cancer driver genes (e.g., TP53 and ERBB2) were primarily found in high-risk tumors, together with APOBEC-related mutational signatures. The identification of subclasses in NMIBC may offer better prognostication and treatment selection based on subclass assignment.
Published: 2016
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9. Identification of expressed and conserved human noncoding RNAs

Author: Nielsen, Morten Muhlig, Tehler, Disa, Vang, Søren, Sudzina, Frantisek, Hedegaard, Jakob, Nordentoft, Iver, Orntoft, Torben Falck, Lund, Anders H., Pedersen, Jakob Skou, Nielsen, Morten Muhlig, Tehler, Disa, Vang, Søren, Sudzina, Frantisek, Hedegaard, Jakob, Nordentoft, Iver, Orntoft, Torben Falck, Lund, Anders H., and Pedersen, Jakob Skou
Abstract: The past decade has shown mammalian genomes to be pervasively transcribed and identified thousands of noncoding (nc) transcripts. It is currently unclear to what extent these transcripts are of functional importance, as experimental functional evidence exists for only a small fraction. Here, we characterize the expression and evolutionary conservation properties of 12,115 known and novel nc transcripts, including structural RNAs, long nc RNAs (lncRNAs), antisense RNAs, EvoFold predictions, ultraconserved elements, and expressed nc regions. Expression levels are evaluated across 12 human tissues using a custom-designed microarray, supplemented with RNAseq. Conservation levels are evaluated at both the base level and at the syntenic level. We combine these measures with epigenetic mark annotations to identify subsets of novel nc transcripts that show characteristics similar to known functional ncRNAs. Few novel nc transcripts show both high expression and conservation levels. However, overall, we observe a positive correlation between expression and both conservation and epigenetic annotations, suggesting that a subset of the expressed transcripts are under purifying selection and likely functional. The identified subsets of expressed and conserved novel nc transcripts may form the basis for further functional characterization.
Published: 2014

10. Pancreatic beta cells activate a JunB/ATF3- dependent survival pathway during inflammation

Author: Gurzov, Esteban Nicolas, Barthson, Jenny, Marhfour, Ihsane, Ortis, Fernanda, Naamane, Najib, Igoillo Esteve, Mariana, Gysemans, Conny, Mathieu, Chantal, Kitajima, S, Marchetti, Piero, Orntoft, Torben Falck, Bakiri, Latifa, Wagner, Erwin F, Eizirik, Decio L., Gurzov, Esteban Nicolas, Barthson, Jenny, Marhfour, Ihsane, Ortis, Fernanda, Naamane, Najib, Igoillo Esteve, Mariana, Gysemans, Conny, Mathieu, Chantal, Kitajima, S, Marchetti, Piero, Orntoft, Torben Falck, Bakiri, Latifa, Wagner, Erwin F, and Eizirik, Decio L.
Abstract: info:eu-repo/semantics/published
Published: 2012

11. Cytokines interleukin-1beta and tumor necrosis factor-alpha regulate different transcriptional and alternative splicing networks in primary beta-cells.

Author: Ortis, Fernanda, Naamane, Najib, Flamez, Daisy, Ladrière, Laurence, Moore, Fabrice, Andrade Da Cunha, Daniel, Colli, Maikel Luis, Thykjaer, Thomas, Thorsen, Kasper, Orntoft, Torben Falck, Eizirik, Decio L., Ortis, Fernanda, Naamane, Najib, Flamez, Daisy, Ladrière, Laurence, Moore, Fabrice, Andrade Da Cunha, Daniel, Colli, Maikel Luis, Thykjaer, Thomas, Thorsen, Kasper, Orntoft, Torben Falck, and Eizirik, Decio L.
Abstract: OBJECTIVE: Cytokines contribute to pancreatic beta-cell death in type 1 diabetes. This effect is mediated by complex gene networks that remain to be characterized. We presently utilized array analysis to define the global expression pattern of genes, including spliced variants, modified by the cytokines interleukin (IL)-1beta + interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha + IFN-gamma in primary rat beta-cells. RESEARCH DESIGN AND METHODS: Fluorescence-activated cell sorter-purified rat beta-cells were exposed to IL-1beta + IFN-gamma or TNF-alpha + IFN-gamma for 6 or 24 h, and global gene expression was analyzed by microarray. Key results were confirmed by RT-PCR, and small-interfering RNAs were used to investigate the mechanistic role of novel and relevant transcription factors identified by pathway analysis. RESULTS Nearly 16,000 transcripts were detected as present in beta-cells, with temporal differences in the number of genes modulated by IL-1beta + IFNgamma or TNF-alpha + IFN-gamma. These cytokine combinations induced differential expression of inflammatory response genes, which is related to differential induction of IFN regulatory factor-7. Both treatments decreased the expression of genes involved in the maintenance of beta-cell phenotype and growth/regeneration. Cytokines induced hypoxia-inducible factor-alpha, which in this context has a proapoptotic role. Cytokines also modified the expression of >20 genes involved in RNA splicing, and exon array analysis showed cytokine-induced changes in alternative splicing of >50% of the cytokine-modified genes. CONCLUSIONS: The present study doubles the number of known genes expressed in primary beta-cells, modified or not by cytokines, and indicates the biological role for several novel cytokine-modified pathways in beta-cells. It also shows that cytokines modify alternative splicing in beta-cells, opening a new avenue of research for the field., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published
Published: 2010

12. Induction of nuclear factor-kappaB and its downstream genes by TNF-alpha and IL-1beta has a pro-apoptotic role in pancreatic beta cells.

Author: Ortis, Fernanda, Pirot, Pierre, Naamane, Najib, Kreins, A Y, Rasschaert, Joanne, Moore, F, Théâtre, E, Verhaeghe, C, Magnusson, N E, Chariot, Alain, Orntoft, Torben Falck, Eizirik, Decio L., Ortis, Fernanda, Pirot, Pierre, Naamane, Najib, Kreins, A Y, Rasschaert, Joanne, Moore, F, Théâtre, E, Verhaeghe, C, Magnusson, N E, Chariot, Alain, Orntoft, Torben Falck, and Eizirik, Decio L.
Abstract: AIMS/HYPOTHESIS: IL-1beta and TNF-alpha contribute to pancreatic beta cell death in type 1 diabetes. Both cytokines activate the transcription factor nuclear factor-kappaB (NF-kappaB), but recent observations suggest that NF-kappaB blockade prevents IL-1beta + IFN-gamma- but not TNF-alpha + IFN-gamma-induced beta cell apoptosis. The aim of the present study was to compare the effects of IL-1beta and TNF-alpha on cell death and the pattern of NF-kappaB activation and global gene expression in beta cells. METHODS: Cell viability was measured after exposure to IL-1beta or to TNF-alpha alone or in combination with IFN-gamma, and blockade of NF-kappaB activation or protein synthesis. INS-1E cells exposed to IL-1beta or TNF-alpha in time course experiments were used for IkappaB kinase (IKK) activation assay, detection of p65 NF-kappaB by immunocytochemistry, real-time RT-PCR and microarray analysis. RESULTS: Blocking NF-kappaB activation protected beta cells against IL-1beta + IFNgamma- or TNFalpha + IFNgamma-induced apoptosis. Blocking de novo protein synthesis did not increase TNF-alpha- or IL-1beta-induced beta cell death, in line with the observations that cytokines induced the expression of the anti-apoptotic genes A20, Iap-2 and Xiap to a similar extent. Microarray analysis of INS-1E cells treated with IL-1beta or TNF-alpha showed similar patterns of gene expression. IL-1beta, however, induced a higher rate of expression of NF-kappaB target genes putatively involved in beta cell dysfunction and death and a stronger activation of the IKK complex, leading to an earlier translocation of NF-kappaB to the nucleus. CONCLUSIONS/INTERPRETATION: NF-kappaB activation in beta cells has a pro-apoptotic role following exposure not only to IL-1beta but also to TNF-alpha. The more marked beta cell death induced by IL-1beta is explained at least in part by higher intensity NF-kappaB activation, leading to increased transcription of key target genes., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published
Published: 2008

13. Secretagogin is a new neuroendocrine marker in the human prostate.

Author: Adolf, Katja, Wagner, Ludwig, Bergh, Anders, Stattin, Pär, Ottosen, Peter, Borre, Michael, Birkenkamp-Demtröder, Karin, Orntoft, Torben Falck, Tørring, Niels, Adolf, Katja, Wagner, Ludwig, Bergh, Anders, Stattin, Pär, Ottosen, Peter, Borre, Michael, Birkenkamp-Demtröder, Karin, Orntoft, Torben Falck, and Tørring, Niels
Published: 2007

14. Global profiling of genes modified by endoplasmic reticulum stress in pancreatic beta cells reveals the early degradation of insulin mRNAs

Author: Pirot, Pierre, Naamane, Najib, Libert, Frédérick, Magnusson, N. E., Orntoft, Torben Falck, Cardozo, Alessandra K, Eizirik, Decio L., Pirot, Pierre, Naamane, Najib, Libert, Frédérick, Magnusson, N. E., Orntoft, Torben Falck, Cardozo, Alessandra K, and Eizirik, Decio L.
Abstract: AIMS/HYPOTHESIS: Pancreatic beta cells respond to endoplasmic reticulum (ER) stress by activating the unfolded protein response. If the stress is prolonged, or the adaptive response fails, apoptosis is triggered. We used a 'homemade' microarray specifically designed for the study of beta cell apoptosis (the APOCHIP) to uncover mechanisms regulating beta cell responses to ER stress. MATERIALS AND METHODS: A time course viability and microarray analysis was performed in insulin-producing INS-1E cells exposed to the reversible ER stress inducer cyclopiazonic acid (CPA). Modification of selected genes was confirmed by real-time RT-PCR, and the observed inhibition of expression of the insulin-1 (Ins1) and insulin-2 (Ins2) genes was further characterised in primary beta cells exposed to a diverse range of agents that induce ER stress. RESULTS: CPA-induced ER stress modified the expression of 183 genes at one or more of the time points studied. The expression of most of these genes returned to control levels after a 3 h recovery period following CPA removal, with all cells surviving. Two groups of genes were particularly affected by CPA, namely, those related to cellular responses to ER stress, which were mostly upregulated, and those related to differentiated beta cell functions, which were downregulated. Levels of Ins1 and Ins2 mRNAs were severely decreased in response to CPA treatment as a result of degradation, and there was a concomitant increase in the level of IRE1 activation. CONCLUSIONS/INTERPRETATION: In this study we provide the first global analysis of beta cell molecular responses to a severe ER stress, and identify the early degradation of mRNA transcripts of the insulin genes as an important component of this response., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published
Published: 2007

15. Construction and validation of the APOCHIP, a spotted oligo-microarray for the study of beta-cell apoptosis.

Author: Magnusson, N. E., Cardozo, Alessandra K, Kruhoffer, M., Eizirik, Decio L., Orntoft, Torben Falck, Jensen, Jan Chr, Magnusson, N. E., Cardozo, Alessandra K, Kruhoffer, M., Eizirik, Decio L., Orntoft, Torben Falck, and Jensen, Jan Chr
Abstract: BACKGROUND: Type 1 diabetes mellitus (T1DM) is a autoimmune disease caused by a long-term negative balance between immune-mediated beta-cell damage and beta-cell repair/regeneration. Following immune-mediated damage the beta-cell fate depends on several genes up- or down-regulated in parallel and/or sequentially. Based on the information obtained by the analysis of several microarray experiments of beta-cells exposed to pro-apoptotic conditions (e.g. double stranded RNA (dsRNA) and cytokines), we have developed a spotted rat oligonucleotide microarray, the APOCHIP, containing 60-mer probes for 574 genes selected for the study of beta-cell apoptosis. RESULTS: The APOCHIP was validated by a combination of approaches. First we performed an internal validation of the spotted probes based on a weighted linear regression model using dilution series experiments. Second we profiled expression measurements in ten dissimilar rat RNA samples for 515 genes that were represented on both the spotted oligonucleotide collection and on the in situ-synthesized 25-mer arrays (Affymetrix GeneChips). Internal validation showed that most of the spotted probes displayed a pattern of reaction close to that predicted by the model. By using simple rules for comparison of data between platforms we found strong correlations (rmedian= 0.84) between relative gene expression measurements made with spotted probes and in situ-synthesized 25-mer probe sets. CONCLUSION: In conclusion our data suggest that there is a high reproducibility of the APOCHIP in terms of technical replication and that relative gene expression measurements obtained with the APOCHIP compare well to the Affymetrix GeneChip. The APOCHIP is available to the scientific community and is a useful tool to study the molecular mechanisms regulating beta-cell apoptosis., Comparative Study, Evaluation Studies, Journal Article, Research Support, Non-U.S. Gov't, Validation Studies, info:eu-repo/semantics/published
Published: 2005

16. Abstract B41: Urinary EN2 levels predict tumor volume in men undergoing radical prostatectomy for prostate cancer

Author: Pandha, Hardev, primary, Sorensen, Karina, additional, Orntoft, Torben Falck, additional, Langley, Stephen, additional, Hoyer, Soren, additional, Borre, Michael, additional, and Morgan, Richard, additional
Published: 2012
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17. Suppressor of cytokine signalling (SOCS)-3 protects beta cells against IL-1beta-mediated toxicity through inhibition of multiple nuclear factor-kappaB-regulated proapoptotic pathways.

Author: Karlsen, A E, Heding, P E, Frobøse, H, Rønn, S G, Kruhøffer, Mogens, Orntoft, Torben Falck, Darville, Martine, Eizirik, Decio L., Pociot, Flemming, Nerup, J, Mandrup-Poulsen, T., Billestrup, N, Karlsen, A E, Heding, P E, Frobøse, H, Rønn, S G, Kruhøffer, Mogens, Orntoft, Torben Falck, Darville, Martine, Eizirik, Decio L., Pociot, Flemming, Nerup, J, Mandrup-Poulsen, T., and Billestrup, N
Abstract: AIMS/HYPOTHESIS: The proinflammatory cytokine IL-1beta induces apoptosis in pancreatic beta cells via pathways dependent on nuclear factor-kappaB (NF-kappaB), mitogen-activated protein kinase, and protein kinase C. We recently showed suppressor of cytokine signalling (SOCS)-3 to be a natural negative feedback regulator of IL-1beta- and IFN-gamma-mediated signalling in rat islets and beta cell lines, preventing their deleterious effects. However, the mechanisms underlying SOCS-3 inhibition of IL-1beta signalling and prevention against apoptosis remain unknown. METHODS: The effect of SOCS-3 expression on the global gene-expression profile following IL-1beta exposure was microarray-analysed using a rat beta cell line (INS-1) with inducible SOCS-3 expression. Subsequently, functional analyses were performed. RESULTS: Eighty-two known genes and several expressed sequence tags (ESTs) changed expression level 2.5-fold or more in response to IL-1beta alone. Following 6 h of IL-1beta exposure, 23 transcripts were up-regulated. Of these, several, including all eight transcripts relating to immune/inflammatory response pathways, were suppressed by SOCS-3. Following 24 h of IL-1beta exposure, secondary response genes were detected, affecting metabolism, energy generation, protein synthesis and degradation, growth arrest, and apoptosis. The majority of these changes were prevented by SOCS-3 expression. Multiple IL-1beta-induced NF-kappaB-dependent proapoptotic early response genes were inhibited by SOCS-3 expression, suggesting that SOCS-3 inhibits NF-kappaB-mediated signalling. These observations were experimentally confirmed in functional analyses. CONCLUSIONS/INTERPRETATION: This study suggests that there is an unexpected cross-talk between the SOCS/IFN and the IL-1beta pathways of signalling in pancreatic beta cells, which could lead to a novel perspective of blocking two important proapoptotic pathways in pancreatic beta cells by influencing a single signalling molecule, na, Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published
Published: 2004

18. Gene microarray study corroborates proteomic findings in rodent islet cells.

Author: Cardozo, Alessandra K, Berthou, L., Kruhoffer, M., Orntoft, Torben Falck, Nicolls, M.R., Eizirik, Decio L., Cardozo, Alessandra K, Berthou, L., Kruhoffer, M., Orntoft, Torben Falck, Nicolls, M.R., and Eizirik, Decio L.
Abstract: As reported in an issue of Journal of Proteome Research, mass spectrometry has been used to identify numerous proteins in pancreatic islets. Our group studies beta cell gene expression, and we were interested in whether proteins described in this study could be found at the level of the transcriptome. Microarray analysis is a powerful technique for quantitative measurements of the expression of thousand genes in parallel. However, in crude tumor biopsies, only a subset of transcripts correlate with protein levels, and it is still unknown how frequently mRNA expression correlates with amount of protein in well-differentiated cells. To address this issue, we presently compared data from mouse primary islet proteins obtained by proteomic analysis with RNA data from FACS purified primary rat beta cells obtained by microarray analysis (Rasschaert J, Liu D, Cardozo AK, Kutlu B, Eizirik DL, manuscript in preparation)., Comment, Comparative Study, Letter, info:eu-repo/semantics/published
Published: 2003

19. Identification of novel cytokine-induced genes in pancreatic beta-cells by high-density oligonucleotide arrays.

Author: Cardozo, Alessandra K, Kruhøffer, Mogens, Leeman, Ruth, Orntoft, Torben Falck, Eizirik, Decio L., Cardozo, Alessandra K, Kruhøffer, Mogens, Leeman, Ruth, Orntoft, Torben Falck, and Eizirik, Decio L.
Abstract: Type 1 diabetes is an autoimmune disease resulting from the selective destruction of insulin-producing beta-cells. Cytokines may contribute to pancreatic beta-cell death in type 1 diabetes. beta-cell exposure to interleukin (IL)-1beta induces functional impairment, whereas beta-cell culture for 6-9 days in the presence of IL-1beta and interferon (INF)-gamma leads to apoptosis. To clarify the mechanisms involved in these effects of cytokines, we studied the general pattern of cytokine-induced gene expression in beta-cells. Primary rat beta-cells were fluorescence-activated cell sorter-purified and exposed for 6 or 24 h to control condition, IL-1beta + INF-gamma, or IL-1beta alone (24 h only). Gene expression profile was analyzed in duplicate by oligonucleotide arrays. Nearly 3,000 transcripts were detected in controls and cytokine-treated beta-cells. Of these, 96 and 147 displayed changes in expression after 6 and 24 h, respectively, of exposure to IL-1beta + INF-gamma, whereas 105 transcripts were modified after a 24-h exposure to IL-1beta. The cytokine-responsive genes were clustered according to their biological functions. The major clusters observed were metabolism, signal transduction, transcription factors, protein synthesis/ processing, hormones, and related receptors. These modifications in gene expression may explain some of the cytokine effects in beta-cells, such as decreased protein biosynthesis and insulin release. In addition, there was induction of diverse cytokines and chemokines; this suggests that beta-cells may contribute to mononuclear cell homing during insulitis. Several of the cytokine-induced genes are potentially regulated by the transcription factor NF-kappaB. Clarification of the function of the identified cytokine-induced gene patterns may unveil some of the mechanisms involved in beta-cell damage and repair in type 1 diabetes., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published
Published: 2001

20. Altered Expression of CLC, DSG3, EMP3, S100A2, and SLPI in Corneal Epithelium from Keratoconus Patients

Author: Nielsen, Kim, primary, Heegaard, Steffen, additional, Vorum, Henrik, additional, Birkenkamp-Demtröder, Karin, additional, Ehlers, Niels, additional, and Orntoft, Torben Falck, additional
Published: 2005
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21. Identification of Differentially Expressed Genes in Keratoconus Epithelium Analyzed on Microarrays

Author: Nielsen, Kim, primary, Birkenkamp-Demtro¨der, Karin, additional, Ehlers, Niels, additional, and Orntoft, Torben Falck, additional
Published: 2003
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22. Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Author: Dadaev, Tokhir, Saunders, Edward J, Newcombe, Paul J, Anokian, Ezequiel, Leongamornlert, Daniel A, Brook, Mark N, Cieza-Borrella, Clara, Mijuskovic, Martina, Wakerell, Sarah, Olama, Ali Amin Al, Schumacher, Fredrick R, Berndt, Sonja I, Benlloch, Sara, Ahmed, Mahbubl, Goh, Chee, Sheng, Xin, Zhang, Zhuo, Muir, Kenneth, Govindasami, Koveela, Lophatananon, Artitaya, Stevens, Victoria L, Gapstur, Susan M, Carter, Brian D, Tangen, Catherine M, Goodman, Phyllis, Thompson, Ian M, Batra, Jyotsna, Chambers, Suzanne, Moya, Leire, Clements, Judith, Horvath, Lisa, Tilley, Wayne, Risbridger, Gail, Gronberg, Henrik, Aly, Markus, Nordström, Tobias, Pharoah, Paul, Pashayan, Nora, Schleutker, Johanna, Tammela, Teuvo LJ, Sipeky, Csilla, Auvinen, Anssi, Albanes, Demetrius, Weinstein, Stephanie, Wolk, Alicja, Hakansson, Niclas, West, Catharine, Dunning, Alison M, Burnet, Neil, Mucci, Lorelei, Giovannucci, Edward, Andriole, Gerald, Cussenot, Olivier, Cancel-Tassin, Géraldine, Koutros, Stella, Freeman, Laura E Beane, Sorensen, Karina Dalsgaard, Orntoft, Torben Falck, Borre, Michael, Maehle, Lovise, Grindedal, Eli Marie, Neal, David E, Donovan, Jenny L, Hamdy, Freddie C, Martin, Richard M, Travis, Ruth C, Key, Tim J, Hamilton, Robert J, Fleshner, Neil E, Finelli, Antonio, Ingles, Sue Ann, Stern, Mariana C, Rosenstein, Barry, Kerns, Sarah, Ostrer, Harry, Lu, Yong-Jie, Zhang, Hong-Wei, Feng, Ninghan, Mao, Xueying, Guo, Xin, Wang, Guomin, Sun, Zan, Giles, Graham G, Southey, Melissa C, MacInnis, Robert J, FitzGerald, Liesel M, Kibel, Adam S, Drake, Bettina F, Vega, Ana, Gómez-Caamaño, Antonio, Fachal, Laura, Szulkin, Robert, Eklund, Martin, Kogevinas, Manolis, Llorca, Javier, Castaño-Vinyals, Gemma, Penney, Kathryn L, Stampfer, Meir, Park, Jong Y, Sellers, Thomas A, Lin, Hui-Yi, Stanford, Janet L, Cybulski, Cezary, Wokolorczyk, Dominika, Lubinski, Jan, Ostrander, Elaine A, Geybels, Milan S, Nordestgaard, Børge G, Nielsen, Sune F, Weisher, Maren, Bisbjerg, Rasmus, Røder, Martin Andreas, Iversen, Peter, Brenner, Hermann, Cuk, Katarina, Holleczek, Bernd, Maier, Christiane, Luedeke, Manuel, Schnoeller, Thomas, Kim, Jeri, Logothetis, Christopher J, John, Esther M, Teixeira, Manuel R, Paulo, Paula, Cardoso, Marta, Neuhausen, Susan L, Steele, Linda, Ding, Yuan Chun, De Ruyck, Kim, De Meerleer, Gert, Ost, Piet, Razack, Azad, Lim, Jasmine, Teo, Soo-Hwang, Lin, Daniel W, Newcomb, Lisa F, Lessel, Davor, Gamulin, Marija, Kulis, Tomislav, Kaneva, Radka, Usmani, Nawaid, Slavov, Chavdar, Mitev, Vanio, Parliament, Matthew, Singhal, Sandeep, Claessens, Frank, Joniau, Steven, Van Den Broeck, Thomas, Larkin, Samantha, Townsend, Paul A, Aukim-Hastie, Claire, Gago-Dominguez, Manuela, Castelao, Jose Esteban, Martinez, Maria Elena, Roobol, Monique J, Jenster, Guido, Van Schaik, Ron HN, Menegaux, Florence, Truong, Thérèse, Koudou, Yves Akoli, Xu, Jianfeng, Khaw, Kay-Tee, Cannon-Albright, Lisa, Pandha, Hardev, Michael, Agnieszka, Kierzek, Andrzej, Thibodeau, Stephen N, McDonnell, Shannon K, Schaid, Daniel J, Lindstrom, Sara, Turman, Constance, Ma, Jing, Hunter, David J, Riboli, Elio, Siddiq, Afshan, Canzian, Federico, Kolonel, Laurence N, Le Marchand, Loic, Hoover, Robert N, Machiela, Mitchell J, Kraft, Peter, PRACTICAL (Prostate Cancer Association Group To Investigate Cancer-Associated Alterations In The Genome) Consortium, Freedman, Matthew, Wiklund, Fredrik, Chanock, Stephen, Henderson, Brian E, Easton, Douglas F, Haiman, Christopher A, Eeles, Rosalind A, Conti, David V, and Kote-Jarai, Zsofia
Subjects: Male, Risk, Quantitative Trait Loci, Black People, Chromosome Mapping, Prostatic Neoplasms, Bayes Theorem, Molecular Sequence Annotation, Polymorphism, Single Nucleotide, White People, 3. Good health, Multivariate Analysis, Humans, Genetic Predisposition to Disease, Algorithms, Genome-Wide Association Study
Abstract: Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling.

23. Author Correction: Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci

Author: Schumacher, Fredrick R., Olama, Ali Amin Al, Berndt, Sonja I., Benlloch, Sara, Ahmed, Mahbubl, Saunders, Edward J., Dadaev, Tokhir, Leongamornlert, Daniel, Anokian, Ezequiel, Cieza-Borrella, Clara, Goh, Chee, Brook, Mark N., Sheng, Xin, Fachal, Laura, Dennis, Joe, Tyrer, Jonathan, Muir, Kenneth, Lophatananon, Artitaya, Stevens, Victoria L., Gapstur, Susan M., Carter, Brian D., Tangen, Catherine M., Goodman, Phyllis J., Thompson, Ian M., Batra, Jyotsna, Chambers, Suzanne, Moya, Leire, Clements, Judith, Horvath, Lisa, Tilley, Wayne, Risbridger, Gail P., Gronberg, Henrik, Aly, Markus, Nordström, Tobias, Pharoah, Paul, Pashayan, Nora, Schleutker, Johanna, Tammela, Teuvo L. J., Sipeky, Csilla, Auvinen, Anssi, Albanes, Demetrius, Weinstein, Stephanie, Wolk, Alicja, Håkansson, Niclas, West, Catharine M. L., Dunning, Alison M., Burnet, Neil, Mucci, Lorelei A., Giovannucci, Edward, Andriole, Gerald L., Cussenot, Olivier, Cancel-Tassin, Géraldine, Koutros, Stella, Beane Freeman, Laura E., Sorensen, Karina Dalsgaard, Orntoft, Torben Falck, Borre, Michael, Maehle, Lovise, Grindedal, Eli Marie, Neal, David E., Donovan, Jenny L., Hamdy, Freddie C., Martin, Richard M., Travis, Ruth C., Key, Tim J., Hamilton, Robert J., Fleshner, Neil E., Finelli, Antonio, Ingles, Sue Ann, Stern, Mariana C., Rosenstein, Barry S., Kerns, Sarah L., Ostrer, Harry, Lu, Yong-Jie, Zhang, Hong-Wei, Feng, Ninghan, Mao, Xueying, Guo, Xin, Wang, Guomin, Sun, Zan, Giles, Graham G., Southey, Melissa C., MacInnis, Robert J., FitzGerald, Liesel M., Kibel, Adam S., Drake, Bettina F., Vega, Ana, Gómez-Caamaño, Antonio, Szulkin, Robert, Eklund, Martin, Kogevinas, Manolis, Llorca, Javier, Castaño-Vinyals, Gemma, Penney, Kathryn L., Stampfer, Meir, Park, Jong Y., Sellers, Thomas A., Lin, Hui-Yi, Stanford, Janet L., Cybulski, Cezary, Wokolorczyk, Dominika, Lubinski, Jan, Ostrander, Elaine A., Geybels, Milan S., Nordestgaard, Børge G., Nielsen, Sune F., Weischer, Maren, Bisbjerg, Rasmus, Røder, Martin Andreas, Iversen, Peter, Brenner, Hermann, Cuk, Katarina, Holleczek, Bernd, Maier, Christiane, Luedeke, Manuel, Schnoeller, Thomas, Kim, Jeri, Logothetis, Christopher J., John, Esther M., Teixeira, Manuel R., Paulo, Paula, Cardoso, Marta, Neuhausen, Susan L., Steele, Linda, Ding, Yuan Chun, De Ruyck, Kim, De Meerleer, Gert, Ost, Piet, Razack, Azad, Lim, Jasmine, Teo, Soo-Hwang, Lin, Daniel W., Newcomb, Lisa F., Lessel, Davor, Gamulin, Marija, Kulis, Tomislav, Kaneva, Radka, Usmani, Nawaid, Singhal, Sandeep, Slavov, Chavdar, Mitev, Vanio, Parliament, Matthew, Claessens, Frank, Joniau, Steven, Van den Broeck, Thomas, Larkin, Samantha, Townsend, Paul A., Aukim-Hastie, Claire, Gago-Dominguez, Manuela, Castelao, Jose Esteban, Martinez, Maria Elena, Roobol, Monique J., Jenster, Guido, van Schaik, Ron H. N., Menegaux, Florence, Truong, Thérèse, Koudou, Yves Akoli, Xu, Jianfeng, Khaw, Kay-Tee, Cannon-Albright, Lisa, Pandha, Hardev, Michael, Agnieszka, Thibodeau, Stephen N., McDonnell, Shannon K., Schaid, Daniel J., Lindstrom, Sara, Turman, Constance, Ma, Jing, Hunter, David J., Riboli, Elio, Siddiq, Afshan, Canzian, Federico, Kolonel, Laurence N., Le Marchand, Loic, Hoover, Robert N., Machiela, Mitchell J., Cui, Zuxi, Kraft, Peter, Amos, Christopher I., Conti, David V., Easton, Douglas F., Wiklund, Fredrik, Chanock, Stephen J., Henderson, Brian E., Kote-Jarai, Zsofia, Haiman, Christopher A., and Eeles, Rosalind A.
Abstract: In the version of this article initially published, the name of author Manuela Gago-Dominguez was misspelled as Manuela Gago Dominguez. The error has been corrected in the HTML and PDF version of the article.
Published: 2019
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24. High miR-449b expression in prostate cancer is associated with biochemical recurrence after radical prostatectomy.

Author: Mortensen, Martin Mørck, Høyer, Søren, Orntoft, Torben Falck, Sørensen, Karina Dalsgaard, Dyrskjøt, Lars, and Borre, Michael
Published: 2014
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25. Identification of expressed and conserved human noncoding RNAs.

Author: Nielsen MM, Tehler D, Vang S, Sudzina F, Hedegaard J, Nordentoft I, Orntoft TF, Lund AH, and Pedersen JS
Subjects: Base Sequence, Chromatin genetics, Conserved Sequence, Expressed Sequence Tags, Humans, Inverted Repeat Sequences, Molecular Sequence Annotation, Oligonucleotide Array Sequence Analysis, Open Reading Frames, Organ Specificity, RNA, Untranslated metabolism, RNA, Untranslated genetics, Transcriptome
Abstract: The past decade has shown mammalian genomes to be pervasively transcribed and identified thousands of noncoding (nc) transcripts. It is currently unclear to what extent these transcripts are of functional importance, as experimental functional evidence exists for only a small fraction. Here, we characterize the expression and evolutionary conservation properties of 12,115 known and novel nc transcripts, including structural RNAs, long nc RNAs (lncRNAs), antisense RNAs, EvoFold predictions, ultraconserved elements, and expressed nc regions. Expression levels are evaluated across 12 human tissues using a custom-designed microarray, supplemented with RNAseq. Conservation levels are evaluated at both the base level and at the syntenic level. We combine these measures with epigenetic mark annotations to identify subsets of novel nc transcripts that show characteristics similar to known functional ncRNAs. Few novel nc transcripts show both high expression and conservation levels. However, overall, we observe a positive correlation between expression and both conservation and epigenetic annotations, suggesting that a subset of the expressed transcripts are under purifying selection and likely functional. The identified subsets of expressed and conserved novel nc transcripts may form the basis for further functional characterization.
Published: 2014
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26. Tumor-promoting macrophages induce the expression of the macrophage-specific receptor CD163 in malignant cells.

Author: Maniecki MB, Etzerodt A, Ulhøi BP, Steiniche T, Borre M, Dyrskjøt L, Orntoft TF, Moestrup SK, and Møller HJ
Subjects: Aged, Aged, 80 and over, Antigens, CD genetics, Antigens, Differentiation, Myelomonocytic genetics, Female, Gene Expression Regulation, Neoplastic, Humans, Interleukin-10 genetics, Interleukin-10 metabolism, Interleukin-6 genetics, Interleukin-6 metabolism, Lymph Nodes metabolism, Lymph Nodes pathology, Macrophages immunology, Male, Middle Aged, Neoplasm Staging, Receptors, Cell Surface genetics, Tumor Microenvironment genetics, Tumor Microenvironment immunology, Urinary Bladder Neoplasms genetics, Urinary Bladder Neoplasms mortality, Urinary Bladder Neoplasms pathology, Antigens, CD metabolism, Antigens, Differentiation, Myelomonocytic metabolism, Macrophages metabolism, Receptors, Cell Surface metabolism, Urinary Bladder Neoplasms metabolism
Abstract: Tumor-associated macrophages (TAMs) represent a distinct malignancy-promoting phenotype suggested to play a key role in tumor formation and metastasis. We aimed to investigate the expression of the monocyte/macrophage-restricted receptor CD163 in bladder tumor biopsies and assess the potential mechanism inducing the CD163 expression in tumor cells. A high CD163 mRNA expression (n = 87) was significantly associated with a poor 13-year overall survival (log-rank test, χ(2) = 8.931; p = 0.0028). Moreover, CD163 mRNA expression was significantly increased in muscle invasive (T2-T4), p = 0.017, and aggressive (grade III/IV) cancers (p = 0.015). The expression strongly correlated with local expression of IL-6 (r = 0.72; p <0.0001) and IL-10 (r = 0.75; p <0.0001), mediators known to induce CD163 expression in vitro. CD163 immunostaining (n = 46) confirmed the association between dense TAM infiltration and histologically advanced disease. In 39% of the biopsies, CD163 immunoreactivity was also observed in tumor cells, and CD163-expressing metastatic cells were identified in lymph node biopsies (n = 8). Bladder cancer cell lines did not express CD163; however, when cocultured with macrophages the bladder cancer cell expression of CD163 was significantly induced in an IL-6/IL-10 independent manner. In conclusion, we show a strong association between CD163 mRNA expression in bladder cancer biopsies and poor patient outcome. CD163 expression was not confined to the infiltrating TAMs, but was also expressed by a significant portion of the malignant cells in both tumors and lymph nodes. CD163 expressing tumor cells may constitute a subpopulation of tumor cells with a phenotypic shift associated with epithelial-to-mesenchymal transition (EMT) and increased metastatic activity induced by TAMs., (Copyright © 2012 UICC.)
Published: 2012
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27. Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study.

Author: Kote-Jarai Z, Olama AA, Giles GG, Severi G, Schleutker J, Weischer M, Campa D, Riboli E, Key T, Gronberg H, Hunter DJ, Kraft P, Thun MJ, Ingles S, Chanock S, Albanes D, Hayes RB, Neal DE, Hamdy FC, Donovan JL, Pharoah P, Schumacher F, Henderson BE, Stanford JL, Ostrander EA, Sorensen KD, Dörk T, Andriole G, Dickinson JL, Cybulski C, Lubinski J, Spurdle A, Clements JA, Chambers S, Aitken J, Gardiner RA, Thibodeau SN, Schaid D, John EM, Maier C, Vogel W, Cooney KA, Park JY, Cannon-Albright L, Brenner H, Habuchi T, Zhang HW, Lu YJ, Kaneva R, Muir K, Benlloch S, Leongamornlert DA, Saunders EJ, Tymrakiewicz M, Mahmud N, Guy M, O'Brien LT, Wilkinson RA, Hall AL, Sawyer EJ, Dadaev T, Morrison J, Dearnaley DP, Horwich A, Huddart RA, Khoo VS, Parker CC, Van As N, Woodhouse CJ, Thompson A, Christmas T, Ogden C, Cooper CS, Lophatonanon A, Southey MC, Hopper JL, English DR, Wahlfors T, Tammela TL, Klarskov P, Nordestgaard BG, Røder MA, Tybjærg-Hansen A, Bojesen SE, Travis R, Canzian F, Kaaks R, Wiklund F, Aly M, Lindstrom S, Diver WR, Gapstur S, Stern MC, Corral R, Virtamo J, Cox A, Haiman CA, Le Marchand L, Fitzgerald L, Kolb S, Kwon EM, Karyadi DM, Orntoft TF, Borre M, Meyer A, Serth J, Yeager M, Berndt SI, Marthick JR, Patterson B, Wokolorczyk D, Batra J, Lose F, McDonnell SK, Joshi AD, Shahabi A, Rinckleb AE, Ray A, Sellers TA, Lin HY, Stephenson RA, Farnham J, Muller H, Rothenbacher D, Tsuchiya N, Narita S, Cao GW, Slavov C, Mitev V, Easton DF, and Eeles RA
Subjects: Adult, Aged, Aged, 80 and over, Case-Control Studies, Cohort Studies, Disease Susceptibility, Genotype, Humans, Male, Middle Aged, Randomized Controlled Trials as Topic, Chromosomes, Human genetics, Genome, Human, Genome-Wide Association Study, Polymorphism, Single Nucleotide genetics, Prostatic Neoplasms genetics, Telomerase genetics
Abstract: Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. We conducted a multi-stage genome-wide association study for PrCa and previously reported the results of the first two stages, which identified 16 PrCa susceptibility loci. We report here the results of stage 3, in which we evaluated 1,536 SNPs in 4,574 individuals with prostate cancer (cases) and 4,164 controls. We followed up ten new association signals through genotyping in 51,311 samples in 30 studies from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. In addition to replicating previously reported loci, we identified seven new prostate cancer susceptibility loci on chromosomes 2p11, 3q23, 3q26, 5p12, 6p21, 12q13 and Xq12 (P = 4.0 × 10(-8) to P = 2.7 × 10(-24)). We also identified a SNP in TERT more strongly associated with PrCa than that previously reported. More than 40 PrCa susceptibility loci, explaining ∼25% of the familial risk in this disease, have now been identified.
Published: 2011
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28. Snail1 is over-expressed in prostate cancer.

Author: Heebøll S, Borre M, Ottosen PD, Dyrskjøt L, Orntoft TF, and Tørring N
Subjects: Cell Nucleus metabolism, Disease Progression, Humans, Immunohistochemistry, Lymphatic Metastasis, Male, Prostatic Hyperplasia pathology, Prostatic Intraepithelial Neoplasia pathology, Prostatic Neoplasms pathology, Snail Family Transcription Factors, Up-Regulation, Prostatic Hyperplasia metabolism, Prostatic Intraepithelial Neoplasia metabolism, Prostatic Neoplasms metabolism, Transcription Factors biosynthesis
Abstract: Transcription factor Snail1 is a mediator of cell migration and survival, and expression is elevated in several cancer types. The Snail1 gene is reportedly amplified in prostate cancer (PC), and we investigated Snail1 expression in PC. Immunohistochemical Snail1 staining was determined on a tissue microarray which includes 327 specimens of PC, 30 specimens from patients with benign prostatic hyperplasia (BPH), benign tissue from 30 PC patients and 15 high-grade prostate intraepithelial neoplasia (high-grade PIN) specimens. Clinicopathological and follow-up data were available for all patients. No BPH specimen and only 21% of benign tissue from PC patients showed high expression of Snail1. Only 7% of high-grade PIN patients expressed a high level of Snail1. In contrast, approximately 50% of PC tissue from patients with PC showed marked nuclear immunostaining. Snail1 immunostaining was significantly associated with Gleason score (p<0.05). Snail1 expression was not correlated to T stage, metastasis at time of diagnosis, risk of or time to recurrence. Snail1 expression was significantly increased in PC with a positive correlation to dedifferentiation, but not to cancer progression or prognosis. The presented data indicate that Snail1 expression is upregulated from the early stages of PC.
Published: 2009
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29. Secretagogin is a new neuroendocrine marker in the human prostate.

Author: Adolf K, Wagner L, Bergh A, Stattin P, Ottosen P, Borre M, Birkenkamp-Demtröder K, Orntoft TF, and Tørring N
Subjects: Aged, Aged, 80 and over, Blotting, Western, Chromogranin A biosynthesis, Humans, Immunohistochemistry, Male, Microscopy, Fluorescence, Middle Aged, Phosphopyruvate Hydratase biosynthesis, Secretagogins, Statistics, Nonparametric, Synaptophysin biosynthesis, Adenocarcinoma metabolism, Biomarkers, Tumor biosynthesis, Calcium-Binding Proteins biosynthesis, Prostatic Neoplasms metabolism
Abstract: Background: Neuroendocrine (NE) differentiation in prostate cancer (PCa), promoted by NE cell secreted products, appears to be associated with tumor progression, poor prognosis, and hormone-refractory disease. We recently reported secretagogin, a hexa-EF-hand Ca(2+) binding protein, as a novel NE marker in carcinoid tumors of the lung and the gastrointestinal tract. The present study analyzes the expression of secretagogin in normal and malign prostate tissue., Methods: We analyzed immunoreactivity for secretagogin, chromogranin A (CgA), neuron specific enolase (NSE), and synaptophysin (SYN) in consecutive sections from 87 formalin-fixed paraffin-embedded (FFPE) benign hyperplastic (n = 10) and prostate adenocarcinoma (n = 77) specimens. The intracellular distribution of secretagogin, CgA, and NSE was examined by confocal fluorescent microscopy, and we characterized secretagogin in eight samples by Western blotting., Results: Secretagogin is cytoplasmic and nuclear expressed in NE and NE differentiated cells, and to a lesser extent in epithelial cells, in the benign prostate and prostate adenocarcinoma cells. Secretagogin stained 82% (46/56) of benign and 71% (48/68) of prostate adenocarcinomas and co-localized with the NE markers CgA and NSE. The expression of secretagogin is significantly correlated to CgA (P < 0.001) and NSE (P < 0.048) in prostate adenocarcinoma and to CgA in normal epithelium (P < 0.028)., Conclusions: Secretagogin is a novel NE marker in the prostate with more extended immunoreactivity compared to the NE markers CgA, SYN, and NSE. Secretagogin is widely expressed in prostatic adenocarcinoma as opposed to adenocarcinomas in other organs.
Published: 2007
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30. Lens epithelium-derived growth factor is an Hsp70-2 regulated guardian of lysosomal stability in human cancer.

Author: Daugaard M, Kirkegaard-Sørensen T, Ostenfeld MS, Aaboe M, Høyer-Hansen M, Orntoft TF, Rohde M, and Jäättelä M
Subjects: Adaptor Proteins, Signal Transducing biosynthesis, Adaptor Proteins, Signal Transducing deficiency, Animals, Breast Neoplasms genetics, Breast Neoplasms pathology, Cell Death physiology, Cell Lineage, Cell Membrane Permeability, Down-Regulation, Female, HSP70 Heat-Shock Proteins deficiency, HeLa Cells, Humans, Lysosomes pathology, Mice, Mice, SCID, Transcription Factors biosynthesis, Transcription Factors deficiency, Transfection, Transplantation, Heterologous, Urinary Bladder Neoplasms genetics, Urinary Bladder Neoplasms pathology, Adaptor Proteins, Signal Transducing physiology, Breast Neoplasms metabolism, HSP70 Heat-Shock Proteins physiology, Lysosomes metabolism, Transcription Factors physiology, Urinary Bladder Neoplasms metabolism
Abstract: Heat shock protein 70-2 (Hsp70-2) is a chaperone protein essential for the growth of spermatocytes and cancer cells. Here, we show that Hsp70-2 depletion triggers lysosomal membrane permeabilization and cathepsin-dependent cell death and identify lens epithelium-derived growth factor (LEDGF) as an Hsp70-2-regulated guardian of lysosomal stability in human cancer. Knockdown of LEDGF in cancer cells induces destabilization of lysosomal membranes followed by caspase-independent and Bcl-2-resistant cell death. Accordingly, ectopic LEDGF stabilizes lysosomes and protects cancer cells against cytotoxicity induced by anticancer agents that trigger the lysosomal cell death pathway. Remarkably, ectopic LEDGF also increases the tumorigenic potential of human cancer cells in immunodeficient mice, and LEDGF expression is increased in human breast and bladder carcinomas correlating with that of Hsp70-2 in invasive bladder cancer. Taken together, these data reveal LEDGF as an oncogenic protein that controls a caspase-independent lysosomal cell death pathway.
Published: 2007
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31. Recent advances in high-throughput molecular marker identification for superficial and invasive bladder cancers.

Author: Dyrskjot L, Zieger K, and Orntoft TF
Subjects: Biomarkers, Tumor genetics, Carcinoma classification, Carcinoma diagnosis, Carcinoma pathology, Female, Gene Expression Profiling, Humans, Male, Neoplasm Invasiveness, Oligonucleotide Array Sequence Analysis, Prognosis, Protein Array Analysis, Urinary Bladder Neoplasms classification, Urinary Bladder Neoplasms pathology, Biomarkers, Tumor analysis, Urinary Bladder Neoplasms diagnosis
Abstract: Bladder cancer is the fifth most common neoplasm in industrialized countries. Due to frequent recurrences of the superficial form of this disease, bladder cancer ranks as one of the most common cancers. Despite the description of a large number of tumor markers for bladder cancers, none have individually contributed to the management of the disease. However, the development of high-throughput techniques for simultaneous assessment of a large number of markers has allowed classification of tumors into clinically relevant molecular subgroups beyond those possible by pathological classification. Here, we review the recent advances in high-throughput molecular marker identification for superficial and invasive bladder cancers.
Published: 2007
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32. Human FK506 binding protein 65 is associated with colorectal cancer.

Author: Olesen SH, Christensen LL, Sørensen FB, Cabezón T, Laurberg S, Orntoft TF, and Birkenkamp-Demtröder K
Subjects: Adenocarcinoma pathology, Adenoma pathology, Aged, Aged, 80 and over, Amino Acid Sequence, Animals, Antibodies, Monoclonal metabolism, Binding Sites, Blotting, Western, COS Cells, Chlorocebus aethiops, Colonic Polyps pathology, Colorectal Neoplasms pathology, Electrophoresis, Gel, Two-Dimensional, Electrophoresis, Polyacrylamide Gel, Female, Gene Expression Regulation, Neoplastic, Humans, Hyperplasia, Immunohistochemistry, Intestinal Mucosa cytology, Isoelectric Point, Male, Microscopy, Fluorescence, Middle Aged, Molecular Sequence Data, Molecular Weight, Polymerase Chain Reaction, Protein Binding, Tacrolimus Binding Proteins analysis, Tacrolimus Binding Proteins chemistry, Transfection, Adenocarcinoma metabolism, Colorectal Neoplasms metabolism, Tacrolimus Binding Proteins metabolism
Abstract: We initiated the present study to identify new genes associated with colorectal cancer. In a previously published microarray study an EST (W80763), later identified as the gene hFKBP10 (NM_021939), was found to be strongly expressed in tumors while absent in the normal mucosa. Here we describe this gene hFKBP10 together with its encoded protein hFKBP65 as a novel marker associated with colorectal cancer. Analysis of 31 colorectal adenocarcinomas and 14 normal colorectal mucosa by RealTime PCR for hFKBP10 showed a significant up-regulation in tumors, when compared with normal mucosa. Immunohistochemical analysis of 26 adenocarcinomas and matching normal mucosa, as well as benign hyperplastic polyps and adenomas, using a monoclonal anti-hFKBP65 antibody, showed that the protein was not present in normal colorectal epithelial cells, but strongly expressed in the tumor cells of colorectal cancer. The protein was also expressed in fibroblasts of both normal mucosa and tumor tissue. Western blot analysis of matched tumors and normal mucosa supported the finding of increased hFKBP65 expression in tumors compared with normal mucosa, in addition to identifying the molecular mass of hFKBP65 to approximately 72 kDa. Cellular localization and glycosylation studies revealed the hFKBP65 protein to be localized in the endoplasmic reticulum, and to be N-glycosylated. In conclusion, the protein hFKBP65 is associated with colorectal cancer, and we hypothesize the protein to be involved in fibroblast and transformed epithelial cell-specific protein synthesis in the endoplasmic reticulum.
Published: 2005
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32 results on '"Orntoft, Torben Falck"'

1. Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci

2. Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

3. A meta-analysis of genome-wide association studies to identify prostate cancer susceptibility loci associated with aggressive and non-aggressive disease

4. Germline variation at 8q24 and prostate cancer risk in men of European ancestry (vol 9, 4616, 2018)

5. Germline variation at 8q24 and prostate cancer risk in men of European ancestry

6. Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci

7. epiG:statistical inference and profiling of DNA methylation from whole-genome bisulfite sequencing data

8. Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma

9. Identification of expressed and conserved human noncoding RNAs

10. Pancreatic beta cells activate a JunB/ATF3- dependent survival pathway during inflammation

11. Cytokines interleukin-1beta and tumor necrosis factor-alpha regulate different transcriptional and alternative splicing networks in primary beta-cells.

12. Induction of nuclear factor-kappaB and its downstream genes by TNF-alpha and IL-1beta has a pro-apoptotic role in pancreatic beta cells.

13. Secretagogin is a new neuroendocrine marker in the human prostate.

14. Global profiling of genes modified by endoplasmic reticulum stress in pancreatic beta cells reveals the early degradation of insulin mRNAs

15. Construction and validation of the APOCHIP, a spotted oligo-microarray for the study of beta-cell apoptosis.

16. Abstract B41: Urinary EN2 levels predict tumor volume in men undergoing radical prostatectomy for prostate cancer

17. Suppressor of cytokine signalling (SOCS)-3 protects beta cells against IL-1beta-mediated toxicity through inhibition of multiple nuclear factor-kappaB-regulated proapoptotic pathways.

18. Gene microarray study corroborates proteomic findings in rodent islet cells.

19. Identification of novel cytokine-induced genes in pancreatic beta-cells by high-density oligonucleotide arrays.

20. Altered Expression of CLC, DSG3, EMP3, S100A2, and SLPI in Corneal Epithelium from Keratoconus Patients

21. Identification of Differentially Expressed Genes in Keratoconus Epithelium Analyzed on Microarrays

22. Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

23. Author Correction: Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci

24. High miR-449b expression in prostate cancer is associated with biochemical recurrence after radical prostatectomy.

25. Identification of expressed and conserved human noncoding RNAs.

26. Tumor-promoting macrophages induce the expression of the macrophage-specific receptor CD163 in malignant cells.

27. Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study.

28. Snail1 is over-expressed in prostate cancer.

29. Secretagogin is a new neuroendocrine marker in the human prostate.

30. Lens epithelium-derived growth factor is an Hsp70-2 regulated guardian of lysosomal stability in human cancer.

31. Recent advances in high-throughput molecular marker identification for superficial and invasive bladder cancers.

32. Human FK506 binding protein 65 is associated with colorectal cancer.

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32 results on '"Orntoft, Torben Falck"'

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