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46 results on '"Obazee, Ofure"'

1. Exome sequencing identifies germline variants in DIS3 in familial multiple myeloma

Author

Pertesi, Maroulio, Vallée, Maxime, Wei, Xiaomu, Revuelta, Maria V., Galia, Perrine, Demangel, Delphine, Oliver, Javier, Foll, Matthieu, Chen, Siwei, Perrial, Emeline, Garderet, Laurent, Corre, Jill, Leleu, Xavier, Boyle, Eileen M., Decaux, Olivier, Rodon, Philippe, Kolb, Brigitte, Slama, Borhane, Mineur, Philippe, Voog, Eric, Le Bris, Catherine, Fontan, Jean, Maigre, Michel, Beaumont, Marie, Azais, Isabelle, Sobol, Hagay, Vignon, Marguerite, Royer, Bruno, Perrot, Aurore, Fuzibet, Jean-Gabriel, Dorvaux, Véronique, Anglaret, Bruno, Cony-Makhoul, Pascale, Berthou, Christian, Desquesnes, Florence, Pegourie, Brigitte, Leyvraz, Serge, Mosser, Laurent, Frenkiel, Nicole, Augeul-Meunier, Karine, Leduc, Isabelle, Leyronnas, Cécile, Voillat, Laurent, Casassus, Philippe, Mathiot, Claire, Cheron, Nathalie, Paubelle, Etienne, Moreau, Philippe, Bignon, Yves–Jean, Joly, Bertrand, Bourquard, Pascal, Caillot, Denis, Naman, Hervé, Rigaudeau, Sophie, Marit, Gérald, Macro, Margaret, Lambrecht, Isabelle, Cliquennois, Manuel, Vincent, Laure, Helias, Philippe, Avet-Loiseau, Hervé, Moreno, Victor, Reis, Rui Manuel, Varkonyi, Judit, Kruszewski, Marcin, Vangsted, Annette Juul, Jurczyszyn, Artur, Zaucha, Jan Maciej, Sainz, Juan, Krawczyk-Kulis, Malgorzata, Wątek, Marzena, Pelosini, Matteo, Iskierka-Jażdżewska, Elzbieta, Grząśko, Norbert, Martinez-Lopez, Joaquin, Jerez, Andrés, Campa, Daniele, Buda, Gabriele, Lesueur, Fabienne, Dudziński, Marek, García-Sanz, Ramón, Nagler, Arnon, Rymko, Marcin, Jamroziak, Krzysztof, Butrym, Aleksandra, Canzian, Federico, Obazee, Ofure, Nilsson, Björn, Klein, Robert J., Lipkin, Steven M., McKay, James D., and Dumontet, Charles

Published
2019
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2. Common genetic variants associated with pancreatic adenocarcinoma may also modify risk of pancreatic neuroendocrine neoplasms

Author

Obazee, Ofure, Capurso, Gabriele, Tavano, Francesca, Archibugi, Livia, De Bonis, Antonio, Greenhalf, William, Key, Tim, Pasquali, Claudio, Milanetto, Anna Caterina, Hackert, Thilo, Fogar, Paola, Liço, Valbona, Dervenis, Christos, Lawlor, Rita T, Landoni, Luca, Gazouli, Maria, Zambon, Carlo Federico, Funel, Niccola, Strobel, Oliver, Jamroziak, Krzysztof, Cantù, Cinzia, Małecka-Panas, Ewa, Landi, Stefano, Neoptolemos, John P, Basso, Daniela, Talar-Wojnarowska, Renata, Rinzivillo, Maria, Andriulli, Angelo, Canzian, Federico, and Campa, Daniele

Published
2018
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3. Confirmation of the reduction of hormone replacement therapy-related breast cancer risk for carriers of the HSD17B1_937_G variant

Author

Obazee, Ofure, Justenhoven, Christina, Winter, Stefan, Chang-Claude, Jenny, Rudolph, Anja, Seibold, Petra, Flesch-Janys, Dieter, Hannelius, Ulf, Li, Jingmei, Humphreys, Keith, Hall, Per, Giles, Graham, Severi, Gianluca, Baglietto, Laura, Southey, Melissa, Rabstein, Sylvia, Harth, Volker, Lotz, Anne, Pesch, Beate, Brüning, Thomas, Baisch, Christian, Ko, Yon-Dschun, Hamann, Ute, and Brauch, Hiltrud

Published
2013
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4. The postmenopausal hormone replacement therapy-related breast cancer risk is decreased in women carrying the CYP2C19*17 variant

Author

Justenhoven, Christina, Obazee, Ofure, Winter, Stefan, Couch, Fergus J., Olson, Janet E., Hall, Per, Hannelius, Ulf, Li, Jingmei, Humphreys, Keith, Severi, Gianluca, Giles, Graham, Southey, Melissa, Baglietto, Laura, Fasching, Peter A., Beckmann, Matthias W., Ekici, Arif B., Hamann, Ute, Baisch, Christian, Harth, Volker, Rabstein, Sylvia, Lotz, Anne, Pesch, Beate, Brüning, Thomas, Ko, Yon-Dschun, and Brauch, Hiltrud

Published
2012
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5. Polygenic and multifactorial scores for pancreatic ductal adenocarcinoma risk prediction

Author

Galeotti, Alice Alessandra Gentiluomo, Manuel Rizzato, Cosmeri and Obazee, Ofure Neoptolemos, John P. Pasquali, Claudio and Nentwich, Michael Cavestro, Giulia Martina Pezzilli, Raffaele and Greenhalf, William Holleczek, Bernd Schroeder, Cornelia and Schottker, Ben Ivanauskas, Audrius Ginocchi, Laura Key, Timothy J. Hegyi, Peter Archibugi, Livia Darvasi, Erika and Basso, Daniela Sperti, Cosimo Bijlsma, Maarten F. Palmieri, Orazio Hlavac, Viktor Talar-Wojnarowska, Renata and Mohelnikova-Duchonova, Beatrice Hackert, Thilo Vashist, Yogesh and Strouhal, Ondrej van Laarhoven, Hanneke Tavano, Francesca and Lovecek, Martin Dervenis, Christos Izbeki, Ferenc and Padoan, Andrea Malecka-Panas, Ewa Maiello, Evaristo Vanella, Giuseppe Capurso, Gabriele Izbicki, Jakob R. Theodoropoulos, George E. Jamroziak, Krzysztof Katzke, Verena Kaaks, Rudolf and Mambrini, Andrea Papanikolaou, Ioannis S. Szmola, Richard and Szentesi, Andrea Kupcinskas, Juozas Bursi, Simona and Costello, Eithne Boggi, Ugo Milanetto, Anna Caterina Landi, Stefano Gazouli, Maria Vodickova, Ludmila Soucek, Pavel and Gioffreda, Domenica Gemignani, Federica Brenner, Hermann and Strobel, Oliver Buechler, Markus Vodicka, Pavel Paiella, Salvatore Canzian, Federico Campa, Daniele

Abstract

Background Most cases of pancreatic ductal adenocarcinoma (PDAC) are asymptomatic in early stages, and the disease is typically diagnosed in advanced phases, resulting in very high mortality. Tools to identify individuals at high risk of developing PDAC would be useful to improve chances of early detection. Objective We generated a polygenic risk score (PRS) for PDAC risk prediction, combining the effect of known risk SNPs, and carried out an exploratory analysis of a multifactorial score. Methods We tested the associations of the individual known risk SNPs on up to 2851 PDAC cases and 4810 controls of European origin from the PANcreatic Disease ReseArch (PANDoRA) consortium. Thirty risk SNPs were included in a PRS, which was computed on the subset of subjects that had 100% call rate, consisting of 839 cases and 2040 controls in PANDoRA and 6420 cases and 4889 controls from the previously published Pancreatic Cancer Cohort Consortium I-III and Pancreatic Cancer Case-Control Consortium genome-wide association studies. Additional exploratory multifactorial scores were constructed by complementing the genetic score with smoking and diabetes. Results The scores were associated with increased PDAC risk and reached high statistical significance (OR=2.70, 95% CI 1.99 to 3.68, p=2.54x10(-10) highest vs lowest quintile of the weighted PRS, and OR=14.37, 95% CI 5.57 to 37.09, p=3.64x10(-8), highest vs lowest quintile of the weighted multifactorial score). Conclusion We found a highly significant association between a PRS and PDAC risk, which explains more than individual SNPs and is a step forward in the direction of the construction of a tool for risk stratification in the population.

Published
2021

7. Polygenic and multifactorial scores for pancreatic ductal adenocarcinoma risk prediction

Author

Galeotti, Alice Alessandra, primary, Gentiluomo, Manuel, additional, Rizzato, Cosmeri, additional, Obazee, Ofure, additional, Neoptolemos, John P, additional, Pasquali, Claudio, additional, Nentwich, Michael, additional, Cavestro, Giulia Martina, additional, Pezzilli, Raffaele, additional, Greenhalf, William, additional, Holleczek, Bernd, additional, Schroeder, Cornelia, additional, Schöttker, Ben, additional, Ivanauskas, Audrius, additional, Ginocchi, Laura, additional, Key, Timothy J, additional, Hegyi, Péter, additional, Archibugi, Livia, additional, Darvasi, Erika, additional, Basso, Daniela, additional, Sperti, Cosimo, additional, Bijlsma, Maarten F, additional, Palmieri, Orazio, additional, Hlavac, Viktor, additional, Talar-Wojnarowska, Renata, additional, Mohelnikova-Duchonova, Beatrice, additional, Hackert, Thilo, additional, Vashist, Yogesh, additional, Strouhal, Ondrej, additional, van Laarhoven, Hanneke, additional, Tavano, Francesca, additional, Lovecek, Martin, additional, Dervenis, Christos, additional, Izbéki, Ferenc, additional, Padoan, Andrea, additional, Małecka-Panas, Ewa, additional, Maiello, Evaristo, additional, Vanella, Giuseppe, additional, Capurso, Gabriele, additional, Izbicki, Jakob R, additional, Theodoropoulos, George E, additional, Jamroziak, Krzysztof, additional, Katzke, Verena, additional, Kaaks, Rudolf, additional, Mambrini, Andrea, additional, Papanikolaou, Ioannis S, additional, Szmola, Richárd, additional, Szentesi, Andrea, additional, Kupcinskas, Juozas, additional, Bursi, Simona, additional, Costello, Eithne, additional, Boggi, Ugo, additional, Milanetto, Anna Caterina, additional, Landi, Stefano, additional, Gazouli, Maria, additional, Vodickova, Ludmila, additional, Soucek, Pavel, additional, Gioffreda, Domenica, additional, Gemignani, Federica, additional, Brenner, Hermann, additional, Strobel, Oliver, additional, Büchler, Markus, additional, Vodicka, Pavel, additional, Paiella, Salvatore, additional, Canzian, Federico, additional, and Campa, Daniele, additional

Published
2020
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8. Genetic polymorphisms in the cag pathogenicity island of Helicobacter pylori and risk of stomach cancer and high‐grade premalignant gastric lesions

Author

Canzian, Federico, primary, Rizzato, Cosmeri, additional, Obazee, Ofure, additional, Stein, Angelika, additional, Flores‐Luna, Lourdes, additional, Camorlinga‐Ponce, Margarita, additional, Mendez‐Tenorio, Alfonso, additional, Vivas, Jorge, additional, Trujillo, Esperanza, additional, Jang, Hyejong, additional, Chen, Wei, additional, Kasamatsu, Elena, additional, Bravo, Maria Mercedes, additional, Torres, Javier, additional, Muñoz, Nubia, additional, and Kato, Ikuko, additional

Published
2020
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9. Genome‐wide association study identifies an early onset pancreatic cancer risk locus

Author

Campa, Daniele, primary, Gentiluomo, Manuel, additional, Obazee, Ofure, additional, Ballerini, Alba, additional, Vodickova, Ludmila, additional, Hegyi, Péter, additional, Soucek, Pavel, additional, Brenner, Hermann, additional, Milanetto, Anna Caterina, additional, Landi, Stefano, additional, Gao, Xin, additional, Bozzato, Dania, additional, Capurso, Gabriele, additional, Tavano, Francesca, additional, Vashist, Yogesh, additional, Hackert, Thilo, additional, Bambi, Franco, additional, Bursi, Simona, additional, Oliverius, Martin, additional, Gioffreda, Domenica, additional, Schöttker, Ben, additional, Ivanauskas, Audrius, additional, Mohelnikova‐Duchonova, Beatrice, additional, Darvasi, Erika, additional, Pezzilli, Raffaele, additional, Małecka‐Panas, Ewa, additional, Strobel, Oliver, additional, Gazouli, Maria, additional, Katzke, Verena, additional, Szentesi, Andrea, additional, Cavestro, Giulia Martina, additional, Farkas, Gyula, additional, Izbicki, Jakob R., additional, Moz, Stefania, additional, Archibugi, Livia, additional, Hlavac, Viktor, additional, Vincze, Áron, additional, Talar‐Wojnarowska, Renata, additional, Rusev, Borislav, additional, Kupcinskas, Juozas, additional, Greenhalf, Bill, additional, Dijk, Frederike, additional, Giese, Nathalia, additional, Boggi, Ugo, additional, Andriulli, Angelo, additional, Busch, Olivier R, additional, Vanella, Giuseppe, additional, Vodicka, Pavel, additional, Nentwich, Michael, additional, Lawlor, Rita T., additional, Theodoropoulos, George E, additional, Jamroziak, Krzysztof, additional, Zuppardo, Raffaella Alessia, additional, Moletta, Lucia, additional, Ginocchi, Laura, additional, Kaaks, Rudolf, additional, Neoptolemos, John P, additional, Lucchesi, Maurizio, additional, and Canzian, Federico, additional

Published
2020
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10. Variations in cag pathogenicity island genes of Helicobacter pylori from Latin American groups may influence neoplastic progression to gastric cancer

Author

Rizzato, Cosmeri, primary, Torres, Javier, additional, Obazee, Ofure, additional, Camorlinga-Ponce, Margarita, additional, Trujillo, Esperanza, additional, Stein, Angelika, additional, Mendez-Tenorio, Alfonso, additional, Bravo, Maria Mercedes, additional, Canzian, Federico, additional, and Kato, Ikuko, additional

Published
2020
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11. A Transcriptome-Wide Association Study Identifies Novel Candidate Susceptibility Genes for Pancreatic Cancer

Author

Zhong, Jun, primary, Jermusyk, Ashley, additional, Wu, Lang, additional, Hoskins, Jason W, additional, Collins, Irene, additional, Mocci, Evelina, additional, Zhang, Mingfeng, additional, Song, Lei, additional, Chung, Charles C, additional, Zhang, Tongwu, additional, Xiao, Wenming, additional, Albanes, Demetrius, additional, Andreotti, Gabriella, additional, Arslan, Alan A, additional, Babic, Ana, additional, Bamlet, William R, additional, Beane-Freeman, Laura, additional, Berndt, Sonja, additional, Borgida, Ayelet, additional, Bracci, Paige M, additional, Brais, Lauren, additional, Brennan, Paul, additional, Bueno-de-Mesquita, Bas, additional, Buring, Julie, additional, Canzian, Federico, additional, Childs, Erica J, additional, Cotterchio, Michelle, additional, Du, Mengmeng, additional, Duell, Eric J, additional, Fuchs, Charles, additional, Gallinger, Steven, additional, Gaziano, J Michael, additional, Giles, Graham G, additional, Giovannucci, Edward, additional, Goggins, Michael, additional, Goodman, Gary E, additional, Goodman, Phyllis J, additional, Haiman, Christopher, additional, Hartge, Patricia, additional, Hasan, Manal, additional, Helzlsouer, Kathy J, additional, Holly, Elizabeth A, additional, Klein, Eric A, additional, Kogevinas, Manolis, additional, Kurtz, Robert J, additional, LeMarchand, Loic, additional, Malats, Núria, additional, Männistö, Satu, additional, Milne, Roger, additional, Neale, Rachel E, additional, Ng, Kimmie, additional, Obazee, Ofure, additional, Oberg, Ann L, additional, Orlow, Irene, additional, Patel, Alpa V, additional, Peters, Ulrike, additional, Porta, Miquel, additional, Rothman, Nathaniel, additional, Scelo, Ghislaine, additional, Sesso, Howard D, additional, Severi, Gianluca, additional, Sieri, Sabina, additional, Silverman, Debra, additional, Sund, Malin, additional, Tjønneland, Anne, additional, Thornquist, Mark D, additional, Tobias, Geoffrey S, additional, Trichopoulou, Antonia, additional, Van Den Eeden, Stephen K, additional, Visvanathan, Kala, additional, Wactawski-Wende, Jean, additional, Wentzensen, Nicolas, additional, White, Emily, additional, Yu, Herbert, additional, Yuan, Chen, additional, Zeleniuch-Jacquotte, Anne, additional, Hoover, Robert, additional, Brown, Kevin, additional, Kooperberg, Charles, additional, Risch, Harvey A, additional, Jacobs, Eric J, additional, Li, Donghui, additional, Yu, Kai, additional, Shu, Xiao-Ou, additional, Chanock, Stephen J, additional, Wolpin, Brian M, additional, Stolzenberg-Solomon, Rachael Z, additional, Chatterjee, Nilanjan, additional, Klein, Alison P, additional, Smith, Jill P, additional, Kraft, Peter, additional, Shi, Jianxin, additional, Petersen, Gloria M, additional, Zheng, Wei, additional, and Amundadottir, Laufey T, additional

Published
2020
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12. A Transcriptome-Wide Association Study Identifies Novel Candidate Susceptibility Genes for Pancreatic Cancer

Author

Zhong, Jun, Jermusyk, Ashley, Wu, Lang, Hoskins, Jason W., Collins, Irene, Mocci, Evelina, Zhang, Mingfeng, Song, Lei, Chung, Charles C., Zhang, Tongwu, Xiao, Wenming, Albanes, Demetrius, Andreotti, Gabriella, Arslan, Alan A., Babic, Ana, Bamlet, William R., Beane-Freeman, Laura, Berndt, Sonja, Borgida, Ayelet, Bracci, Paige M., Brais, Lauren, Brennan, Paul, Bueno-de-Mesquita, Bas, Buring, Julie, Canzian, Federico, Childs, Erica J., Cotterchio, Michelle, Du, Mengmeng, Duell, Eric J., Fuchs, Charles, Gallinger, Steven, Gaziano, J. Michael, Giles, Graham G., Giovannucci, Edward, Goggins, Michael, Goodman, Gary E., Goodman, Phyllis J., Haiman, Christopher, Hartge, Patricia, Hasan, Manal, Helzlsouer, Kathy J., Holly, Elizabeth A., Klein, Eric A., Kogevinas, Manolis, Kurtz, Robert J., LeMarchand, Loic, Malats, Nuria, Mannisto, Satu, Milne, Roger, Neale, Rachel E., Ng, Kimmie, Obazee, Ofure, Oberg, Ann L., Orlow, Irene, Patel, Alpa, V, Peters, Ulrike, Porta, Miquel, Rothman, Nathaniel, Scelo, Ghislaine, Sesso, Howard D., Severi, Gianluca, Sieri, Sabina, Silverman, Debra, Sund, Malin, Tjonneland, Anne, Thornquist, Mark D., Tobias, Geoffrey S., Trichopoulou, Antonia, Van den Eeden, Stephen K., Visvanathan, Kala, Wactawski-Wende, Jean, Wentzensen, Nicolas, White, Emily, Yu, Herbert, Yuan, Chen, Zeleniuch-Jacquotte, Anne, Hoover, Robert, Brown, Kevin, Kooperberg, Charles, Risch, Harvey A., Jacobs, Eric J., Li, Donghui, Yu, Kai, Shu, Xiao-Ou, Chanock, Stephen J., Wolpin, Brian M., Stolzenberg-Solomon, Rachael Z., Chatterjee, Nilanjan, Klein, Alison P., Smith, Jill P., Kraft, Peter, Shi, Jianxin, Petersen, Gloria M., Zheng, Wei, Amundadottir, Laufey T., Zhong, Jun, Jermusyk, Ashley, Wu, Lang, Hoskins, Jason W., Collins, Irene, Mocci, Evelina, Zhang, Mingfeng, Song, Lei, Chung, Charles C., Zhang, Tongwu, Xiao, Wenming, Albanes, Demetrius, Andreotti, Gabriella, Arslan, Alan A., Babic, Ana, Bamlet, William R., Beane-Freeman, Laura, Berndt, Sonja, Borgida, Ayelet, Bracci, Paige M., Brais, Lauren, Brennan, Paul, Bueno-de-Mesquita, Bas, Buring, Julie, Canzian, Federico, Childs, Erica J., Cotterchio, Michelle, Du, Mengmeng, Duell, Eric J., Fuchs, Charles, Gallinger, Steven, Gaziano, J. Michael, Giles, Graham G., Giovannucci, Edward, Goggins, Michael, Goodman, Gary E., Goodman, Phyllis J., Haiman, Christopher, Hartge, Patricia, Hasan, Manal, Helzlsouer, Kathy J., Holly, Elizabeth A., Klein, Eric A., Kogevinas, Manolis, Kurtz, Robert J., LeMarchand, Loic, Malats, Nuria, Mannisto, Satu, Milne, Roger, Neale, Rachel E., Ng, Kimmie, Obazee, Ofure, Oberg, Ann L., Orlow, Irene, Patel, Alpa, V, Peters, Ulrike, Porta, Miquel, Rothman, Nathaniel, Scelo, Ghislaine, Sesso, Howard D., Severi, Gianluca, Sieri, Sabina, Silverman, Debra, Sund, Malin, Tjonneland, Anne, Thornquist, Mark D., Tobias, Geoffrey S., Trichopoulou, Antonia, Van den Eeden, Stephen K., Visvanathan, Kala, Wactawski-Wende, Jean, Wentzensen, Nicolas, White, Emily, Yu, Herbert, Yuan, Chen, Zeleniuch-Jacquotte, Anne, Hoover, Robert, Brown, Kevin, Kooperberg, Charles, Risch, Harvey A., Jacobs, Eric J., Li, Donghui, Yu, Kai, Shu, Xiao-Ou, Chanock, Stephen J., Wolpin, Brian M., Stolzenberg-Solomon, Rachael Z., Chatterjee, Nilanjan, Klein, Alison P., Smith, Jill P., Kraft, Peter, Shi, Jianxin, Petersen, Gloria M., Zheng, Wei, and Amundadottir, Laufey T.

Abstract

Background: Although 20 pancreatic cancer susceptibility loci have been identified through genome-wide association studies in individuals of European ancestry, much of its heritability remains unexplained and the genes responsible largely unknown. Methods: To discover novel pancreatic cancer risk loci and possible causal genes, we performed a pancreatic cancer transcriptome-wide association study in Europeans using three approaches: FUSION, MetaXcan, and Summary-MulTiXcan. We integrated genome-wide association studies summary statistics from 9040 pancreatic cancer cases and 12 496 controls, with gene expression prediction models built using transcriptome data from histologically normal pancreatic tissue samples (NCI Laboratory of Translational Genomics [n = 95] and Genotype-Tissue Expression v7 [n = 174] datasets) and data from 48 different tissues (Genotype-Tissue Expression v7, n = 74-421 samples). Results: We identified 25 genes whose genetically predicted expression was statistically significantly associated with pancreatic cancer risk (false discovery rate < .05), including 14 candidate genes at 11 novel loci (1p36.12: CELA3B; 9q31.1: SMC2, SMC2-AS1; 10q23.31: RP11-80H5.9; 12q13.13: SMUG1; 14q32.33: BTBD6; 15q23: HEXA; 15q26.1: RCCD1; 17q12: PNMT, CDK12, PGAP3; 17q22: SUPT4H1; 18q11.22: RP11-888D10.3; and 19p13.11: PGPEPI) and 11 at six known risk loci (5p15.33: TERT, CLPTMIL, ZDHHCIIB; 7p14.1: INHBA; 9q34.2: ABO; 13q12.2: PDX1; 13q22.1: KLF5; and 16q23.1: WDR59, CFDP1, BCAR1, TMEM170A). The association for 12 of these genes (CELA3B, SMC2, and PNMT at novel risk loci and TERT, CLPTMIL, INHBA, ABO, PDX1, KLF5, WDR59, CFDP1, and BCAR1 at known loci) remained statistically significant after Bonferroni correction. Conclusions: By integrating gene expression and genotype data, we identified novel pancreatic cancer risk loci and candidate functional genes that warrant further investigation.

Published
2020
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16. A multifactorial score for pancreatic ductal adenocarcinoma risk prediction

Author

Gentiluomo, Manuel, primary, Galeotti, Alice Alessandra, additional, Rizzato, Cosmeri, additional, Obazee, Ofure, additional, Neoptolemos, John P., additional, Pasquali, Claudio, additional, Nentwich, Michael, additional, Cavestro, Giulia Martina, additional, Pezzilli, Raffaele, additional, Greenhalf, William, additional, Holleczek, Bernd, additional, Schroeder, Cornelia, additional, Schöttker, Ben, additional, Ivanauskas, Audrius, additional, Ginocchi, Laura, additional, Key, Timothy J., additional, Hegyi, Péter, additional, Archibugi, Livia, additional, Darvasi, Erika, additional, Basso, Daniela, additional, Sperti, Cosimo, additional, Bijlsma, Maarten F., additional, Palmieri, Orazio, additional, Hlavac, Viktor, additional, Talar-Wojnarowska, Renata, additional, Mohelnikova-Duchonova, Beatrice, additional, Hackert, Thilo, additional, Vashist, Yogesh, additional, Strouhal, Ondrej, additional, van Laarhoven, Hanneke, additional, Tavano, Francesca, additional, Lovecek, Martin, additional, Dervenis, Christos, additional, Izbéki, Ferenc, additional, Padoan, Andrea, additional, Małecka-Panas, Ewa, additional, Maiello, Evaristo, additional, Vanella, Giuseppe, additional, Capurso, Gabriele, additional, Izbicki, Jakob R., additional, Theodoropoulos, George E., additional, Jamroziak, Krzysztof, additional, Katzke, Verena, additional, Kaaks, Rudolf, additional, Mambrini, Andrea, additional, Papanikolaou, Ioannis S., additional, Szmola, Richárd, additional, Szentesi, Andrea, additional, Kupcinskas, Juozas, additional, Bursi, Simona, additional, Costello, Eithne, additional, Boggi, Ugo, additional, Milanetto, Anna Caterina, additional, Landi, Stefano, additional, Gazouli, Maria, additional, Vodickova, Ludmila, additional, Soucek, Pavel, additional, Gioffreda, Domenica, additional, Gemignani, Federica, additional, Brenner, Hermann, additional, Strobel, Oliver, additional, Büchler, Markus W., additional, Vodicka, Pavel, additional, Paiella, Salvatore, additional, Canzian, Federico, additional, and Campa, Daniele, additional

Published
2019
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17. Polygenic and multifactorial scores for pancreatic ductal adenocarcinoma risk prediction.

Author

Galeotti, Alice Alessandra, Gentiluomo, Manuel, Rizzato, Cosmeri, Obazee, Ofure, Neoptolemos, John P., Pasquali, Claudio, Nentwich, Michael, Cavestro, Giulia Martina, Pezzilli, Raffaele, Greenhalf, William, Holleczek, Bernd, Schroeder, Cornelia, Schöttker, Ben, Ivanauskas, Audrius, Ginocchi, Laura, Key, Timothy J., Hegyi, Péter, Archibugi, Livia, Darvasi, Erika, and Basso, Daniela

Published
2021
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18. Exome sequencing identifies germline variants in DIS3 in familial multiple myeloma.

Author

UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'hématologie, Pertesi, Maroulio, Vallée, Maxime, Wei, Xiaomu, Revuelta, Maria V, Galia, Perrine, Demangel, Delphine, Oliver, Javier, Foll, Matthieu, Chen, Siwei, Perrial, Emeline, Garderet, Laurent, Corre, Jill, Leleu, Xavier, Boyle, Eileen M, Decaux, Olivier, Rodon, Philippe, Kolb, Brigitte, Slama, Borhane, Mineur, Philippe, Voog, Eric, Le Bris, Catherine, Fontan, Jean, Maigre, Michel, Beaumont, Marie, Azais, Isabelle, Sobol, Hagay, Vignon, Marguerite, Royer, Bruno, Perrot, Aurore, Fuzibet, Jean-Gabriel, Dorvaux, Véronique, Anglaret, Bruno, Cony-Makhoul, Pascale, Berthou, Christian, Desquesnes, Florence, Pegourie, Brigitte, Leyvraz, Serge, Mosser, Laurent, Frenkiel, Nicole, Augeul-Meunier, Karine, Leduc, Isabelle, Leyronnas, Cécile, Voillat, Laurent, Casassus, Philippe, Mathiot, Claire, Cheron, Nathalie, Paubelle, Etienne, Moreau, Philippe, Bignon, Yves-Jean, Joly, Bertrand, Bourquard, Pascal, Caillot, Denis, Naman, Hervé, Rigaudeau, Sophie, Marit, Gérald, Macro, Margaret, Lambrecht, Isabelle, Cliquennois, Manuel, Vincent, Laure, Helias, Philippe, Avet-Loiseau, Hervé, Moreno, Victor, Reis, Rui Manuel, Varkonyi, Judit, Kruszewski, Marcin, Vangsted, Annette Juul, Jurczyszyn, Artur, Zaucha, Jan Maciej, Sainz, Juan, Krawczyk-Kulis, Malgorzata, Wątek, Marzena, Pelosini, Matteo, Iskierka-Jażdżewska, Elzbieta, Grząśko, Norbert, Martinez-Lopez, Joaquin, Jerez, Andrés, Campa, Daniele, Buda, Gabriele, Lesueur, Fabienne, Dudziński, Marek, García-Sanz, Ramón, Nagler, Arnon, Rymko, Marcin, Jamroziak, Krzysztof, Butrym, Aleksandra, Canzian, Federico, Obazee, Ofure, Nilsson, Björn, Klein, Robert J, Lipkin, Steven M, McKay, James D, Dumontet, Charles, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'hématologie, Pertesi, Maroulio, Vallée, Maxime, Wei, Xiaomu, Revuelta, Maria V, Galia, Perrine, Demangel, Delphine, Oliver, Javier, Foll, Matthieu, Chen, Siwei, Perrial, Emeline, Garderet, Laurent, Corre, Jill, Leleu, Xavier, Boyle, Eileen M, Decaux, Olivier, Rodon, Philippe, Kolb, Brigitte, Slama, Borhane, Mineur, Philippe, Voog, Eric, Le Bris, Catherine, Fontan, Jean, Maigre, Michel, Beaumont, Marie, Azais, Isabelle, Sobol, Hagay, Vignon, Marguerite, Royer, Bruno, Perrot, Aurore, Fuzibet, Jean-Gabriel, Dorvaux, Véronique, Anglaret, Bruno, Cony-Makhoul, Pascale, Berthou, Christian, Desquesnes, Florence, Pegourie, Brigitte, Leyvraz, Serge, Mosser, Laurent, Frenkiel, Nicole, Augeul-Meunier, Karine, Leduc, Isabelle, Leyronnas, Cécile, Voillat, Laurent, Casassus, Philippe, Mathiot, Claire, Cheron, Nathalie, Paubelle, Etienne, Moreau, Philippe, Bignon, Yves-Jean, Joly, Bertrand, Bourquard, Pascal, Caillot, Denis, Naman, Hervé, Rigaudeau, Sophie, Marit, Gérald, Macro, Margaret, Lambrecht, Isabelle, Cliquennois, Manuel, Vincent, Laure, Helias, Philippe, Avet-Loiseau, Hervé, Moreno, Victor, Reis, Rui Manuel, Varkonyi, Judit, Kruszewski, Marcin, Vangsted, Annette Juul, Jurczyszyn, Artur, Zaucha, Jan Maciej, Sainz, Juan, Krawczyk-Kulis, Malgorzata, Wątek, Marzena, Pelosini, Matteo, Iskierka-Jażdżewska, Elzbieta, Grząśko, Norbert, Martinez-Lopez, Joaquin, Jerez, Andrés, Campa, Daniele, Buda, Gabriele, Lesueur, Fabienne, Dudziński, Marek, García-Sanz, Ramón, Nagler, Arnon, Rymko, Marcin, Jamroziak, Krzysztof, Butrym, Aleksandra, Canzian, Federico, Obazee, Ofure, Nilsson, Björn, Klein, Robert J, Lipkin, Steven M, McKay, James D, and Dumontet, Charles

Abstract

To the Editor, Multiple myeloma (MM) is the third most common hematological malignancy, after Non-Hodgkin Lymphoma and Leukemia. MM is generally preceded by Monoclonal Gammopathy of Undetermined Significance (MGUS) [1], and epidemiological studies have identified older age, male gender, family history, and MGUS as risk factors for developing MM [...]

Published
2019

20. Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study

Author

Campa, Daniele, primary, Matarazzi, Martina, additional, Greenhalf, William, additional, Bijlsma, Maarten, additional, Saum, Kai-Uwe, additional, Pasquali, Claudio, additional, van Laarhoven, Hanneke, additional, Szentesi, Andrea, additional, Federici, Francesca, additional, Vodicka, Pavel, additional, Funel, Niccola, additional, Pezzilli, Raffaele, additional, Bueno-de-Mesquita, H. Bas, additional, Vodickova, Ludmila, additional, Basso, Daniela, additional, Obazee, Ofure, additional, Hackert, Thilo, additional, Soucek, Pavel, additional, Cuk, Katarina, additional, Kaiser, Jörg, additional, Sperti, Cosimo, additional, Lovecek, Martin, additional, Capurso, Gabriele, additional, Mohelnikova-Duchonova, Beatrice, additional, Khaw, Kay-Tee, additional, König, Anna-Katharina, additional, Kupcinskas, Juozas, additional, Kaaks, Rudolf, additional, Bambi, Franco, additional, Archibugi, Livia, additional, Mambrini, Andrea, additional, Cavestro, Giulia Martina, additional, Landi, Stefano, additional, Hegyi, Péter, additional, Izbicki, Jakob R., additional, Gioffreda, Domenica, additional, Zambon, Carlo Federico, additional, Tavano, Francesca, additional, Talar-Wojnarowska, Renata, additional, Jamroziak, Krzysztof, additional, Key, Timothy J., additional, Fave, Gianfranco Delle, additional, Strobel, Oliver, additional, Jonaitis, Laimas, additional, Andriulli, Angelo, additional, Lawlor, Rita T., additional, Pirozzi, Felice, additional, Katzke, Verena, additional, Valsuani, Chiara, additional, Vashist, Yogesh K., additional, Brenner, Hermann, additional, and Canzian, Federico, additional

Published
2018
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21. Genetic variability of the ABCC2 gene and overall survival in pancreatic cancer

Author

Gentiluomo, Manuel, primary, Galeotti, Alice, additional, Pezzilli, Raffaele, additional, Boggi, Ugo, additional, Capurso, Gabriele, additional, Małecka-Panas, Ewa, additional, Kupcinskas, Juozas, additional, Büchler, Markus, additional, Andriulli, Angelo, additional, Greenhalf, William, additional, Neoptolemos, John P., additional, Mambrini, Andrea, additional, Scarpa, Aldo, additional, Soucek, Pavel, additional, Lovecek, Martin, additional, Mohelnikova-Duchonova, Beatrice, additional, García, Paula Puchalt, additional, Obazee, Ofure, additional, Pasquali, Claudio, additional, Busch, Olivier, additional, Izbicki, Jakob R., additional, Vashist, Yogesh K., additional, Cavestro, Giulia M., additional, Hegyi, Peter, additional, Canzian, Federico, additional, and Campa, Daniele, additional

Published
2018
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22. The PANcreatic DISEASE ReseArch (PANDoRA) consortium: an update

Author

Canzian, Federico, primary, Obazee, Ofure, additional, Hackert, Thilo, additional, Neoptolemos, John P., additional, Strobel, Oliver, additional, Vashist, Yogesh K., additional, Izbicki, Jakob R., additional, Kaaks, Rudolf, additional, Brenner, Hermann, additional, Hegyi, Peter, additional, Boggi, Ugo, additional, Morelli, Luca, additional, Bambi, Franco, additional, Capurso, Gabriele, additional, Pezzilli, Raffaele, additional, Mambrini, Andrea, additional, Sperti, Cosimo, additional, Scarpa, Aldo, additional, Andriulli, Angelo, additional, Cavestro, Giulia Martina, additional, Arcidiacono, Paolo G., additional, Zerbi, Alessandro, additional, Greenhalf, William, additional, Key, Timothy J., additional, Khaw, Kay-Tee, additional, Vodicka, Pavel, additional, Soucek, Pavel, additional, Mohelnikova-Duchonova, Beatrice, additional, Lovecek, Martin, additional, Malecka-Panas, Ewa, additional, Jamroziak, Krzysztof, additional, Kupcinskas, Juozas, additional, Gazouli, Maria, additional, Busch, Olivier, additional, van Eijck, Casper H.J., additional, Bueno-de-Mesquita, H. Bas, additional, Peeters, Petra H.M., additional, Johansen, Julia S., additional, Gubergrits, Natalya, additional, Matsuo, Keitaro, additional, Kikuchi, Shogo, additional, and Campa, Daniele, additional

Published
2018
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23. Novel pancreatic cancer susceptibility loci discovered through genome-wide association studies

Author

Canzian, Federico, primary, Campa, Daniele, additional, Obazee, Ofure, additional, Rizzato, Cosmeri, additional, Gazouli, Maria, additional, Cavestro, Giulia Martina, additional, Scarpa, Aldo, additional, Moz, Stefania, additional, Pezzilli, Raffaele, additional, Mambrini, Andrea, additional, Boggi, Ugo, additional, Capurso, Gabriele, additional, Archibugi, Livia, additional, Bambi, Franco, additional, Andriulli, Angelo, additional, Soucek, Pavel, additional, Vodicka, Pavel, additional, Mohelnikova-Duchonova, Beatrice, additional, Lovecek, Martin, additional, Hackert, Thilo, additional, Neoptolemos, John P., additional, Strobel, Oliver, additional, Vashist, Yogesh K., additional, Izbicki, Jakob R., additional, Kaaks, Rudolf, additional, Brenner, Hermann, additional, Hegyi, Peter, additional, Busch, Olivier, additional, Bueno-de-Mesquita, H. Bas, additional, Peeters, Petra H.M., additional, Malecka-Panas, Ewa, additional, Jamroziak, Krzysztof, additional, Kupcinskas, Juozas, additional, Costello, Eithne, additional, Khaw, Kay-Tee, additional, Key, Timothy J., additional, Stolzenberg-Solomon, Rachael, additional, Wolpin, Brian, additional, Klein, Alison P., additional, and Amundadottir, Laufey T., additional

Published
2018
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24. Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer

Author

Klein, Alison P., Wolpin, Brian M., Risch, Harvey A., Stolzenberg-Solomon, Rachael Z., Mocci, Evelina, Zhang, Mingfeng, Canzian, Federico, Childs, Erica J., Hoskins, Jason W., Jermusyk, Ashley, Zhong, Jun, Chen, Fei, Albanes, Demetrius, Andreotti, Gabriella, Arslan, Alan A., Babic, Ana, Bamlet, William R., Beane-Freeman, Laura, Berndt, Sonja I., Blackford, Amanda, Borges, Michael, Borgida, Ayelet, Bracci, Paige M., Brais, Lauren, Brennan, Paul, Brenner, Hermann, Bueno-de-Mesquita, Bas, Buring, Julie, Campa, Daniele, Capurso, Gabriele, Cavestro, Giulia Martina, Chaffee, Kari G., Chung, Charles C., Cleary, Sean, Cotterchio, Michelle, Dijk, Frederike, Duell, Eric J., Foretova, Lenka, Fuchs, Charles, Funel, Niccola, Gallinger, Steven, Gaziano, J. Michael M., Gazouli, Maria, Giles, Graham G., Giovannucci, Edward, Goggins, Michael, Goodman, Gary E., Goodman, Phyllis J., Hackert, Thilo, Haiman, Christopher, Hartge, Patricia, Hasan, Manal, Hegyi, Peter, Helzlsouer, Kathy J., Herman, Joseph, Holcatova, Ivana, Holly, Elizabeth A., Hoover, Robert, Hung, Rayjean J., Jacobs, Eric J., Jamroziak, Krzysztof, Janout, Vladimir, Kaaks, Rudolf, Khaw, Kay-Tee, Klein, Eric A., Kogevinas, Manolis, Kooperberg, Charles, Kulke, Matthew H., Kupcinskas, Juozas, Kurtz, Robert J., Laheru, Daniel, Landi, Stefano, Lawlor, Rita T., Lee, I. -Min, LeMarchand, Loic, Lu, Lingeng, Malats, Nuria, Mambrini, Andrea, Mannisto, Satu, Milne, Roger L., Mohelnikova-Duchonova, Beatrice, Neale, Rachel E., Neoptolemos, John P., Oberg, Ann L., Olson, Sara H., Orlow, Irene, Pasquali, Claudio, Patel, Alpa V., Peters, Ulrike, Pezzilli, Raffaele, Porta, Miquel, Real, Francisco X., Rothman, Nathaniel, Scelo, Ghislaine, Sesso, Howard D., Severi, Gianluca, Shu, Xiao-Ou, Silverman, Debra, Smith, Jill P., Soucek, Pavel, Sund, Malin, Talar-Wojnarowska, Renata, Tavano, Francesca, Thornquist, Mark D., Tobias, Geoffrey S., Van Den Eeden, Stephen K., Vashist, Yogesh, Visvanathan, Kala, Vodicka, Pavel, Wactawski-Wende, Jean, Wang, Zhaoming, Wentzensen, Nicolas, White, Emily, Yu, Herbert, Yu, Kai, Zeleniuch-Jacquotte, Anne, Zheng, Wei, Kraft, Peter, Li, Donghui, Chanock, Stephen, Obazee, Ofure, Petersen, Gloria M., Amundadottir, Laufey T., Klein, Alison P., Wolpin, Brian M., Risch, Harvey A., Stolzenberg-Solomon, Rachael Z., Mocci, Evelina, Zhang, Mingfeng, Canzian, Federico, Childs, Erica J., Hoskins, Jason W., Jermusyk, Ashley, Zhong, Jun, Chen, Fei, Albanes, Demetrius, Andreotti, Gabriella, Arslan, Alan A., Babic, Ana, Bamlet, William R., Beane-Freeman, Laura, Berndt, Sonja I., Blackford, Amanda, Borges, Michael, Borgida, Ayelet, Bracci, Paige M., Brais, Lauren, Brennan, Paul, Brenner, Hermann, Bueno-de-Mesquita, Bas, Buring, Julie, Campa, Daniele, Capurso, Gabriele, Cavestro, Giulia Martina, Chaffee, Kari G., Chung, Charles C., Cleary, Sean, Cotterchio, Michelle, Dijk, Frederike, Duell, Eric J., Foretova, Lenka, Fuchs, Charles, Funel, Niccola, Gallinger, Steven, Gaziano, J. Michael M., Gazouli, Maria, Giles, Graham G., Giovannucci, Edward, Goggins, Michael, Goodman, Gary E., Goodman, Phyllis J., Hackert, Thilo, Haiman, Christopher, Hartge, Patricia, Hasan, Manal, Hegyi, Peter, Helzlsouer, Kathy J., Herman, Joseph, Holcatova, Ivana, Holly, Elizabeth A., Hoover, Robert, Hung, Rayjean J., Jacobs, Eric J., Jamroziak, Krzysztof, Janout, Vladimir, Kaaks, Rudolf, Khaw, Kay-Tee, Klein, Eric A., Kogevinas, Manolis, Kooperberg, Charles, Kulke, Matthew H., Kupcinskas, Juozas, Kurtz, Robert J., Laheru, Daniel, Landi, Stefano, Lawlor, Rita T., Lee, I. -Min, LeMarchand, Loic, Lu, Lingeng, Malats, Nuria, Mambrini, Andrea, Mannisto, Satu, Milne, Roger L., Mohelnikova-Duchonova, Beatrice, Neale, Rachel E., Neoptolemos, John P., Oberg, Ann L., Olson, Sara H., Orlow, Irene, Pasquali, Claudio, Patel, Alpa V., Peters, Ulrike, Pezzilli, Raffaele, Porta, Miquel, Real, Francisco X., Rothman, Nathaniel, Scelo, Ghislaine, Sesso, Howard D., Severi, Gianluca, Shu, Xiao-Ou, Silverman, Debra, Smith, Jill P., Soucek, Pavel, Sund, Malin, Talar-Wojnarowska, Renata, Tavano, Francesca, Thornquist, Mark D., Tobias, Geoffrey S., Van Den Eeden, Stephen K., Vashist, Yogesh, Visvanathan, Kala, Vodicka, Pavel, Wactawski-Wende, Jean, Wang, Zhaoming, Wentzensen, Nicolas, White, Emily, Yu, Herbert, Yu, Kai, Zeleniuch-Jacquotte, Anne, Zheng, Wei, Kraft, Peter, Li, Donghui, Chanock, Stephen, Obazee, Ofure, Petersen, Gloria M., and Amundadottir, Laufey T.

Abstract

In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 x 10(-8)). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PAN-DoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 x 10(-14)), rs2941471 at 8q21.11 (HNF4G, P = 6.60 x 10(-10)), rs4795218 at 17q12 (HNF1B, P = 1.32 x 10(-8)), and rs1517037 at 18q21.32 (GRP, P = 3.28 x 10(-8)). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene.

Published
2018
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25. Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer

Author

MS MDL 1, Klein, Alison P., Wolpin, Brian M., Risch, Harvey A., Stolzenberg-Solomon, Rachael Z., Mocci, Evelina, Zhang, Mingfeng, Canzian, Federico, Childs, Erica J., Hoskins, Jason W., Jermusyk, Ashley, Zhong, Jun, Chen, Fei, Albanes, Demetrius, Andreotti, Gabriella, Arslan, Alan A., Babic, Ana, Bamlet, William R., Beane-Freeman, Laura, Berndt, Sonja I., Blackford, Amanda, Borges, Michael, Borgida, Ayelet, Bracci, Paige M., Brais, Lauren, Brennan, Paul, Brenner, Hermann, Bueno-De-Mesquita, Bas, Buring, Julie, Campa, Daniele, Capurso, Gabriele, Cavestro, Giulia Martina, Chaffee, Kari G., Chung, Charles C., Cleary, Sean, Cotterchio, Michelle, Dijk, Frederike, Duell, Eric J., Foretova, Lenka, Fuchs, Charles, Funel, Niccola, Gallinger, Steven, Gaziano, J. Michael M., Gazouli, Maria, Giles, Graham G., Giovannucci, Edward, Goggins, Michael, Goodman, Gary E., Goodman, Phyllis J., Hackert, Thilo, Haiman, Christopher, Hartge, Patricia, Hasan, Manal, Hegyi, Peter, Helzlsouer, Kathy J., Herman, Joseph, Holcatova, Ivana, Holly, Elizabeth A., Hoover, Robert, Hung, Rayjean J., Jacobs, Eric J., Jamroziak, Krzysztof, Janout, Vladimir, Kaaks, Rudolf, Khaw, Kay Tee, Klein, Eric A., Kogevinas, Manolis, Kooperberg, Charles, Kulke, Matthew H., Kupcinskas, Juozas, Kurtz, Robert J., Laheru, Daniel, Landi, Stefano, Lawlor, Rita T., Lee, I. Min, Lemarchand, Loic, Lu, Lingeng, Malats, Núria, Mambrini, Andrea, Mannisto, Satu, Milne, Roger L., Mohelníková-Duchoňová, Beatrice, Neale, Rachel E., Neoptolemos, John P., Oberg, Ann L., Olson, Sara H., Orlow, Irene, Pasquali, Claudio, Patel, Alpa V., Peters, Ulrike, Pezzilli, Raffaele, Porta, Miquel, Real, Francisco X., Rothman, Nathaniel, Scelo, Ghislaine, Sesso, Howard D., Severi, Gianluca, Shu, Xiao Ou, Silverman, Debra, Smith, Jill P., Soucek, Pavel, Sund, Malin, Talar-Wojnarowska, Renata, Tavano, Francesca, Thornquist, Mark D., Tobias, Geoffrey S., Van Den Eeden, Stephen K., Vashist, Yogesh, Visvanathan, Kala, Vodicka, Pavel, Wactawski-Wende, Jean, Wang, Zhaoming, Wentzensen, Nicolas, White, Emily, Yu, Herbert, Yu, Kai, Zeleniuch-Jacquotte, Anne, Zheng, Wei, Kraft, Peter, Li, Donghui, Chanock, Stephen, Obazee, Ofure, Petersen, Gloria M., Amundadottir, Laufey T., MS MDL 1, Klein, Alison P., Wolpin, Brian M., Risch, Harvey A., Stolzenberg-Solomon, Rachael Z., Mocci, Evelina, Zhang, Mingfeng, Canzian, Federico, Childs, Erica J., Hoskins, Jason W., Jermusyk, Ashley, Zhong, Jun, Chen, Fei, Albanes, Demetrius, Andreotti, Gabriella, Arslan, Alan A., Babic, Ana, Bamlet, William R., Beane-Freeman, Laura, Berndt, Sonja I., Blackford, Amanda, Borges, Michael, Borgida, Ayelet, Bracci, Paige M., Brais, Lauren, Brennan, Paul, Brenner, Hermann, Bueno-De-Mesquita, Bas, Buring, Julie, Campa, Daniele, Capurso, Gabriele, Cavestro, Giulia Martina, Chaffee, Kari G., Chung, Charles C., Cleary, Sean, Cotterchio, Michelle, Dijk, Frederike, Duell, Eric J., Foretova, Lenka, Fuchs, Charles, Funel, Niccola, Gallinger, Steven, Gaziano, J. Michael M., Gazouli, Maria, Giles, Graham G., Giovannucci, Edward, Goggins, Michael, Goodman, Gary E., Goodman, Phyllis J., Hackert, Thilo, Haiman, Christopher, Hartge, Patricia, Hasan, Manal, Hegyi, Peter, Helzlsouer, Kathy J., Herman, Joseph, Holcatova, Ivana, Holly, Elizabeth A., Hoover, Robert, Hung, Rayjean J., Jacobs, Eric J., Jamroziak, Krzysztof, Janout, Vladimir, Kaaks, Rudolf, Khaw, Kay Tee, Klein, Eric A., Kogevinas, Manolis, Kooperberg, Charles, Kulke, Matthew H., Kupcinskas, Juozas, Kurtz, Robert J., Laheru, Daniel, Landi, Stefano, Lawlor, Rita T., Lee, I. Min, Lemarchand, Loic, Lu, Lingeng, Malats, Núria, Mambrini, Andrea, Mannisto, Satu, Milne, Roger L., Mohelníková-Duchoňová, Beatrice, Neale, Rachel E., Neoptolemos, John P., Oberg, Ann L., Olson, Sara H., Orlow, Irene, Pasquali, Claudio, Patel, Alpa V., Peters, Ulrike, Pezzilli, Raffaele, Porta, Miquel, Real, Francisco X., Rothman, Nathaniel, Scelo, Ghislaine, Sesso, Howard D., Severi, Gianluca, Shu, Xiao Ou, Silverman, Debra, Smith, Jill P., Soucek, Pavel, Sund, Malin, Talar-Wojnarowska, Renata, Tavano, Francesca, Thornquist, Mark D., Tobias, Geoffrey S., Van Den Eeden, Stephen K., Vashist, Yogesh, Visvanathan, Kala, Vodicka, Pavel, Wactawski-Wende, Jean, Wang, Zhaoming, Wentzensen, Nicolas, White, Emily, Yu, Herbert, Yu, Kai, Zeleniuch-Jacquotte, Anne, Zheng, Wei, Kraft, Peter, Li, Donghui, Chanock, Stephen, Obazee, Ofure, Petersen, Gloria M., and Amundadottir, Laufey T.

Published
2018

26. Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer

Author

Klein, Alison P., primary, Wolpin, Brian M., additional, Risch, Harvey A., additional, Stolzenberg-Solomon, Rachael Z., additional, Mocci, Evelina, additional, Zhang, Mingfeng, additional, Canzian, Federico, additional, Childs, Erica J., additional, Hoskins, Jason W., additional, Jermusyk, Ashley, additional, Zhong, Jun, additional, Chen, Fei, additional, Albanes, Demetrius, additional, Andreotti, Gabriella, additional, Arslan, Alan A., additional, Babic, Ana, additional, Bamlet, William R., additional, Beane-Freeman, Laura, additional, Berndt, Sonja I., additional, Blackford, Amanda, additional, Borges, Michael, additional, Borgida, Ayelet, additional, Bracci, Paige M., additional, Brais, Lauren, additional, Brennan, Paul, additional, Brenner, Hermann, additional, Bueno-de-Mesquita, Bas, additional, Buring, Julie, additional, Campa, Daniele, additional, Capurso, Gabriele, additional, Cavestro, Giulia Martina, additional, Chaffee, Kari G., additional, Chung, Charles C., additional, Cleary, Sean, additional, Cotterchio, Michelle, additional, Dijk, Frederike, additional, Duell, Eric J., additional, Foretova, Lenka, additional, Fuchs, Charles, additional, Funel, Niccola, additional, Gallinger, Steven, additional, M. Gaziano, J. Michael, additional, Gazouli, Maria, additional, Giles, Graham G., additional, Giovannucci, Edward, additional, Goggins, Michael, additional, Goodman, Gary E., additional, Goodman, Phyllis J., additional, Hackert, Thilo, additional, Haiman, Christopher, additional, Hartge, Patricia, additional, Hasan, Manal, additional, Hegyi, Peter, additional, Helzlsouer, Kathy J., additional, Herman, Joseph, additional, Holcatova, Ivana, additional, Holly, Elizabeth A., additional, Hoover, Robert, additional, Hung, Rayjean J., additional, Jacobs, Eric J., additional, Jamroziak, Krzysztof, additional, Janout, Vladimir, additional, Kaaks, Rudolf, additional, Khaw, Kay-Tee, additional, Klein, Eric A., additional, Kogevinas, Manolis, additional, Kooperberg, Charles, additional, Kulke, Matthew H., additional, Kupcinskas, Juozas, additional, Kurtz, Robert J., additional, Laheru, Daniel, additional, Landi, Stefano, additional, Lawlor, Rita T., additional, Lee, I.-Min, additional, LeMarchand, Loic, additional, Lu, Lingeng, additional, Malats, Núria, additional, Mambrini, Andrea, additional, Mannisto, Satu, additional, Milne, Roger L., additional, Mohelníková-Duchoňová, Beatrice, additional, Neale, Rachel E., additional, Neoptolemos, John P., additional, Oberg, Ann L., additional, Olson, Sara H., additional, Orlow, Irene, additional, Pasquali, Claudio, additional, Patel, Alpa V., additional, Peters, Ulrike, additional, Pezzilli, Raffaele, additional, Porta, Miquel, additional, Real, Francisco X., additional, Rothman, Nathaniel, additional, Scelo, Ghislaine, additional, Sesso, Howard D., additional, Severi, Gianluca, additional, Shu, Xiao-Ou, additional, Silverman, Debra, additional, Smith, Jill P., additional, Soucek, Pavel, additional, Sund, Malin, additional, Talar-Wojnarowska, Renata, additional, Tavano, Francesca, additional, Thornquist, Mark D., additional, Tobias, Geoffrey S., additional, Van Den Eeden, Stephen K., additional, Vashist, Yogesh, additional, Visvanathan, Kala, additional, Vodicka, Pavel, additional, Wactawski-Wende, Jean, additional, Wang, Zhaoming, additional, Wentzensen, Nicolas, additional, White, Emily, additional, Yu, Herbert, additional, Yu, Kai, additional, Zeleniuch-Jacquotte, Anne, additional, Zheng, Wei, additional, Kraft, Peter, additional, Li, Donghui, additional, Chanock, Stephen, additional, Obazee, Ofure, additional, Petersen, Gloria M., additional, and Amundadottir, Laufey T., additional

Published
2018
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27. Common genetic variants associated with pancreatic adenocarcinoma may also modify risk of pancreatic neuroendocrine neoplasms

Author

Obazee, Ofure, primary, Capurso, Gabriele, additional, Tavano, Francesca, additional, Archibugi, Livia, additional, De Bonis, Antonio, additional, Greenhalf, William, additional, Key, Tim, additional, Pasquali, Claudio, additional, Milanetto, Anna Caterina, additional, Hackert, Thilo, additional, Fogar, Paola, additional, Liço, Valbona, additional, Dervenis, Christos, additional, Lawlor, Rita T, additional, Landoni, Luca, additional, Gazouli, Maria, additional, Zambon, Carlo Federico, additional, Funel, Niccola, additional, Strobel, Oliver, additional, Jamroziak, Krzysztof, additional, Cantù, Cinzia, additional, Małecka-Panas, Ewa, additional, Landi, Stefano, additional, Neoptolemos, John P, additional, Basso, Daniela, additional, Talar-Wojnarowska, Renata, additional, Rinzivillo, Maria, additional, Andriulli, Angelo, additional, Canzian, Federico, additional, and Campa, Daniele, additional

Published
2017
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28. Lack of Association for Reported Endocrine Pancreatic Cancer Risk Loci in the PANDoRA Consortium

Author

Campa, Daniele, primary, Obazee, Ofure, additional, Pastore, Manuela, additional, Panzuto, Francesco, additional, Liço, Valbona, additional, Greenhalf, William, additional, Katzke, Verena, additional, Tavano, Francesca, additional, Costello, Eithne, additional, Corbo, Vincenzo, additional, Talar-Wojnarowska, Renata, additional, Strobel, Oliver, additional, Zambon, Carlo Federico, additional, Neoptolemos, John P., additional, Zerboni, Giulia, additional, Kaaks, Rudolf, additional, Key, Timothy J., additional, Lombardo, Carlo, additional, Jamroziak, Krzysztof, additional, Gioffreda, Domenica, additional, Hackert, Thilo, additional, Khaw, Kay-Tee, additional, Landi, Stefano, additional, Milanetto, Anna Caterina, additional, Landoni, Luca, additional, Lawlor, Rita T., additional, Bambi, Franco, additional, Pirozzi, Felice, additional, Basso, Daniela, additional, Pasquali, Claudio, additional, Capurso, Gabriele, additional, and Canzian, Federico, additional

Published
2017
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29. Rare BRCA2 K3326X increases susceptibility to sporadic pancreatic ductal adenocarcinoma: A PANDoRA study

Author

Obazee, Ofure, primary, Carpurso, Gabriele, additional, Adriulli, Angelo, additional, Soucek, Pavel, additional, Malecka-Panas, Ewa, additional, Kupcinskas, Juozas, additional, Kaaks, Rudolf, additional, Gazouli, Maria, additional, Hackert, Thilo, additional, Lawlor, Rita T., additional, Cavestro, Giulia Martina, additional, Pasquali, Claudio, additional, Brenner, Hermann, additional, Campa, Daniele, additional, Pezzilli, Raffaelle, additional, Mambrini, Andrea, additional, Mohelnikova-Duchonova, Beatrice, additional, Boggi, Ugo, additional, Izbicki, Jakob R., additional, Vodicka, Pavel, additional, Iskierka-Jazdzewska, Elzbieta, additional, and Canzian, Federico, additional

Published
2017
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30. Genetic determinants of telomere length and risk of pancreatic cancer: a PANDoRA study

Author

Campa, Daniele, primary, Matarazzi, Martina, additional, Pezzilli, Raffaele, additional, Boggi, Ugo, additional, Capurso, Gabriele, additional, Talar-Wojnarowska, Renata, additional, Kupcinskas, Juozas, additional, Hackert, Thilo, additional, Vodicka, Pavel, additional, Brenner, Hermann, additional, Khaw, Kay-Tee, additional, Key, Timothy J., additional, Landi, Stefano, additional, Rizzato, Cosmeri, additional, Tavano, Francesca, additional, Gentiluomo, Manuel, additional, Costello, Eithne, additional, Mambrini, Andrea, additional, Lawlor, Rita T., additional, Soucek, Pavel, additional, Kaaks, Rudolf, additional, Milanetto, Anna Caterina, additional, Obazee, Ofure, additional, Dijk, Frederike, additional, Vashist, Yogesh K., additional, Cavestro, Giulia M., additional, Hegyi, Peter, additional, and Canzian, Federico, additional

Published
2017
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31. Do pancreatic adenocarcinomas and neuroendocrine neoplasms share genetic susceptibility a PANDoRA study

Author

Canzian, Federico, primary, Capurso, Gabriele, additional, Andriulli, Angelo, additional, Neoptolemos, John P., additional, Malecka-Panas, Ewa, additional, Kaaks, Rudolf, additional, Gazouli, Maria, additional, Strobel, Oliver, additional, Scarpa, Aldo, additional, Pasquali, Claudio, additional, Landi, Stefano, additional, Boggi, Ugo, additional, Khaw, Kay-Tee, additional, Key, Tim J., additional, Campa, Daniele, additional, and Obazee, Ofure, additional

Published
2017
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32. Abstract 3411: Rare BRCA2 K3326X increases susceptibility to sporadic pancreatic ductal adenocarcinoma: a PANDoRA study

Author

Obazee, Ofure M., primary, Capurso, Gabriele, additional, Andriulli, Angelo, additional, Soucek, Pavel, additional, Panas, Ewa Małecka-, additional, Kupcinskas, Juozas, additional, Kaaks, Rudolf, additional, Gazouli, Maria, additional, Hackert, Thilo, additional, Scarpa, Aldo, additional, Cavestro, Giulia M., additional, Pasquali, Claudio, additional, Brenner, Hermann, additional, Campa, Daniele, additional, Pezzilli, Raffaele, additional, Mambrini, Andrea, additional, Duchonova, Beatrice Mohelnikova-, additional, Boggi, Ugo, additional, Izbicki, Jakob, additional, Vodicka, Pavel, additional, Iskierka-Jazdzewska, Elzbieta, additional, and Canzian, Federico, additional

Published
2017
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33. Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study.

Author

Campa, Daniele, Matarazzi, Martina, Greenhalf, William, Bijlsma, Maarten, Saum, Kai‐Uwe, Pasquali, Claudio, Laarhoven, Hanneke, Szentesi, Andrea, Federici, Francesca, Vodicka, Pavel, Funel, Niccola, Pezzilli, Raffaele, Bueno‐de‐Mesquita, H. Bas, Vodickova, Ludmila, Basso, Daniela, Obazee, Ofure, Hackert, Thilo, Soucek, Pavel, Cuk, Katarina, and Kaiser, Jörg

Abstract

Telomere deregulation is a hallmark of cancer. Telomere length measured in lymphocytes (LTL) has been shown to be a risk marker for several cancers. For pancreatic ductal adenocarcinoma (PDAC) consensus is lacking whether risk is associated with long or short telomeres. Mendelian randomization approaches have shown that a score built from SNPs associated with LTL could be used as a robust risk marker. We explored this approach in a large scale study within the PANcreatic Disease ReseArch (PANDoRA) consortium. We analyzed 10 SNPs (ZNF676‐rs409627, TERT‐rs2736100, CTC1‐rs3027234, DHX35‐rs6028466, PXK‐rs6772228, NAF1‐rs7675998, ZNF208‐rs8105767, OBFC1‐rs9420907, ACYP2‐rs11125529 and TERC‐rs10936599) alone and combined in a LTL genetic score ("teloscore", which explains 2.2% of the telomere variability) in relation to PDAC risk in 2,374 cases and 4,326 controls. We identified several associations with PDAC risk, among which the strongest were with the TERT‐rs2736100 SNP (OR = 1.54; 95%CI 1.35–1.76; p = 1.54 × 10−10) and a novel one with the NAF1‐rs7675998 SNP (OR = 0.80; 95%CI 0.73–0.88; p = 1.87 × 10−6, ptrend = 3.27 × 10−7). The association of short LTL, measured by the teloscore, with PDAC risk reached genome‐wide significance (p = 2.98 × 10−9 for highest vs. lowest quintile; p = 1.82 × 10−10 as a continuous variable). In conclusion, we present a novel genome‐wide candidate SNP for PDAC risk (TERT‐rs2736100), a completely new signal (NAF1‐rs7675998) approaching genome‐wide significance and we report a strong association between the teloscore and risk of pancreatic cancer, suggesting that telomeres are a potential risk factor for pancreatic cancer. What's new? How does lymphocyte telomere length affect pancreatic cancer risk? These authors analyzed 10 SNPs associated with telomere length and their relationship with pancreatic cancer risk, using data from the Pancreatic Disease Research (PANDoRA) consortium. Each patient received a "teloscore" based on the combined SNP data, and it turned out that a low teloscore ‐ predicting a short telomere ‐ was associated with increased pancreatic cancer risk. The researchers also identified for the first time a significant genome‐wide association between a SNP, TERT‐rs2736100, and increased pancreatic cancer risk. They also discovered a completely novel association between a SNP, NAF1‐rs7675998, and decreased risk. [ABSTRACT FROM AUTHOR]

Published
2019
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34. Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21

Author

Zhang, Mingfeng, Wang, Zhaoming, Obazee, Ofure, Jia, Jinping, Childs, Erica J., Hoskins, Jason, Figlioli, Gisella, Mocci, Evelina, Collins, Irene, Chung, Charles C., Hautman, Christopher, Arslan, Alan A., Beane-Freeman, Laura, Bracci, Paige M., Buring, Julie, Duell, Eric J., Gallinger, Steven, Giles, Graham G., Goodman, Gary E., Goodman, Phyllis J., Kamineni, Aruna, Kolonel, Laurence N., Kulke, Matthew H., Malats, Nuria, Olson, Sara H., Sesso, Howard D., Visvanathan, Kala, White, Emily, Zheng, Wei, Abnet, Christian C., Albanes, Demetrius, Andreotti, Gabriella, Brais, Lauren, Bueno-de-Mesquita, H. Bas, Basso, Daniela, Berndt, Sonja I., Boutron-Ruault, Marie-Christine, Bijlsma, Maarten F., Brenner, Hermann, Burdette, Laurie, Campa, Daniele, Caporaso, Neil E., Capurso, Gabriele, Cavestro, Giulia Martina, Cotterchio, Michelle, Costello, Eithne, Elena, Joanne, Boggi, Ugo, Gaziano, J. Michael, Gazouli, Maria, Giovannucci, Edward L., Goggins, Michael, Gross, Myron, Haiman, Christopher A., Hassan, Manal, Helzlsouer, Kathy J., Hu, Nan, Hunter, David J., Iskierka-Jazdzewska, Elzbieta, Jenab, Mazda, Kaaks, Rudolf, Key, Timothy J., Khaw, Kay-Tee, Klein, Eric A., Kogevinas, Manolis, Krogh, Vittorio, Kupcinskas, Juozas, Kurtz, Robert C., Landi, Maria T., Landi, Stefano, Le Marchand, Loic, Mambrini, Andrea, Mannisto, Satu, Milne, Roger L., Neale, Rachel E., Oberg, Ann L., Panico, Salvatore, Patel, Alpa V., Peeters, Petra H. M., Peters, Ulrike, Pezzilli, Raffaele, Porta, Miquel, Purdue, Mark, Ramon Quiros, J., Riboli, Elio, Rothman, Nathaniel, Scarpa, Aldo, Scelo, Ghislaine, Shu, Xiao-Ou, Silverman, Debra T., Soucek, Pavel, Strobel, Oliver, Sund, Malin, Malecka-Panas, Ewa, Taylor, Philip R., Tavano, Francesca, Travis, Ruth C., Thornquist, Mark, Tjonneland, Anne, Tobias, Geoffrey S., Trichopoulos, Dimitrios, Vashist, Yogesh, Vodicka, Pavel, Wactawski-Wende, Jean, Wentzensen, Nicolas, Yu, Herbert, Yu, Kai, Zeleniuch-Jacquotte, Anne, Kooperberg, Charles, Risch, Harvey A., Jacobs, Eric J., Li, Donghui, Fuchs, Charles, Hoover, Robert, Hartge, Patricia, Chanock, Stephen J., Petersen, Gloria M., Stolzenberg-Solomon, Rachael S., Wolpin, Brian M., Kraft, Peter, Klein, Alison P., Canzian, Federico, Amundadottir, Laufey T., Zhang, Mingfeng, Wang, Zhaoming, Obazee, Ofure, Jia, Jinping, Childs, Erica J., Hoskins, Jason, Figlioli, Gisella, Mocci, Evelina, Collins, Irene, Chung, Charles C., Hautman, Christopher, Arslan, Alan A., Beane-Freeman, Laura, Bracci, Paige M., Buring, Julie, Duell, Eric J., Gallinger, Steven, Giles, Graham G., Goodman, Gary E., Goodman, Phyllis J., Kamineni, Aruna, Kolonel, Laurence N., Kulke, Matthew H., Malats, Nuria, Olson, Sara H., Sesso, Howard D., Visvanathan, Kala, White, Emily, Zheng, Wei, Abnet, Christian C., Albanes, Demetrius, Andreotti, Gabriella, Brais, Lauren, Bueno-de-Mesquita, H. Bas, Basso, Daniela, Berndt, Sonja I., Boutron-Ruault, Marie-Christine, Bijlsma, Maarten F., Brenner, Hermann, Burdette, Laurie, Campa, Daniele, Caporaso, Neil E., Capurso, Gabriele, Cavestro, Giulia Martina, Cotterchio, Michelle, Costello, Eithne, Elena, Joanne, Boggi, Ugo, Gaziano, J. Michael, Gazouli, Maria, Giovannucci, Edward L., Goggins, Michael, Gross, Myron, Haiman, Christopher A., Hassan, Manal, Helzlsouer, Kathy J., Hu, Nan, Hunter, David J., Iskierka-Jazdzewska, Elzbieta, Jenab, Mazda, Kaaks, Rudolf, Key, Timothy J., Khaw, Kay-Tee, Klein, Eric A., Kogevinas, Manolis, Krogh, Vittorio, Kupcinskas, Juozas, Kurtz, Robert C., Landi, Maria T., Landi, Stefano, Le Marchand, Loic, Mambrini, Andrea, Mannisto, Satu, Milne, Roger L., Neale, Rachel E., Oberg, Ann L., Panico, Salvatore, Patel, Alpa V., Peeters, Petra H. M., Peters, Ulrike, Pezzilli, Raffaele, Porta, Miquel, Purdue, Mark, Ramon Quiros, J., Riboli, Elio, Rothman, Nathaniel, Scarpa, Aldo, Scelo, Ghislaine, Shu, Xiao-Ou, Silverman, Debra T., Soucek, Pavel, Strobel, Oliver, Sund, Malin, Malecka-Panas, Ewa, Taylor, Philip R., Tavano, Francesca, Travis, Ruth C., Thornquist, Mark, Tjonneland, Anne, Tobias, Geoffrey S., Trichopoulos, Dimitrios, Vashist, Yogesh, Vodicka, Pavel, Wactawski-Wende, Jean, Wentzensen, Nicolas, Yu, Herbert, Yu, Kai, Zeleniuch-Jacquotte, Anne, Kooperberg, Charles, Risch, Harvey A., Jacobs, Eric J., Li, Donghui, Fuchs, Charles, Hoover, Robert, Hartge, Patricia, Chanock, Stephen J., Petersen, Gloria M., Stolzenberg-Solomon, Rachael S., Wolpin, Brian M., Kraft, Peter, Klein, Alison P., Canzian, Federico, and Amundadottir, Laufey T.

Abstract

Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10(-15)), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10(-9)) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10(-8)). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 (NR5A2), chr8q24.21 (MYC) and chr5p15.33 (CLPTM1L-TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal (n = 10) and tumor (n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10(-8)). This finding was validated in a second set of paired (n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10(-4)-2.0x10(-3)). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology.

Published
2016
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35. Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21

Author

MS MDL 1, Epi Kanker Team 1, JC onderzoeksprogramma Kanker, Cancer, Zhang, Mingfeng, Wang, Zhaoming, Obazee, Ofure, Jia, Jinping, Childs, Erica J, Hoskins, Jason, Figlioli, Gisella, Mocci, Evelina, Collins, Irene, Chung, Charles C, Hautman, Christopher, Arslan, Alan A, Beane-Freeman, Laura, Bracci, Paige M, Buring, Julie, Duell, Eric J, Gallinger, Steven, Giles, Graham G, Goodman, Gary E, Goodman, Phyllis J, Kamineni, Aruna, Kolonel, Laurence N, Kulke, Matthew H, Malats, Núria, Olson, Sara H, Sesso, Howard D, Visvanathan, Kala, White, Emily, Zheng, Wei, Abnet, Christian C, Albanes, Demetrius, Andreotti, Gabriella, Brais, Lauren, Bueno-de-Mesquita, H Bas, Basso, Daniela, Berndt, Sonja I, Boutron-Ruault, Marie-Christine, Bijlsma, Maarten F, Brenner, Hermann, Burdette, Laurie, Campa, Daniele, Caporaso, Neil E, Capurso, Gabriele, Cavestro, Giulia Martina, Cotterchio, Michelle, Costello, Eithne, Elena, Joanne, Boggi, Ugo, Gaziano, J Michael, Gazouli, Maria, Giovannucci, Edward L, Goggins, Michael, Gross, Myron, Haiman, Christopher A, Hassan, Manal, Helzlsouer, Kathy J, Hu, Nan, Hunter, David J, Iskierka-Jazdzewska, Elzbieta, Jenab, Mazda, Kaaks, Rudolf, Key, Timothy J, Khaw, Kay-Tee, Klein, Eric A, Kogevinas, Manolis, Krogh, Vittorio, Kupcinskas, Juozas, Kurtz, Robert C, Landi, Maria T, Landi, Stefano, Le Marchand, Loic, Mambrini, Andrea, Mannisto, Satu, Milne, Roger L, Neale, Rachel E, Oberg, Ann L, Panico, Salvatore, Patel, Alpa V, Peeters, Petra H M, Peters, Ulrike, Pezzilli, Raffaele, Porta, Miquel, Purdue, Mark, Quiros, J Ramón, Riboli, Elio, Rothman, Nathaniel, Scarpa, Aldo, Scelo, Ghislaine, Shu, Xiao-Ou, Silverman, Debra T, Soucek, Pavel, Strobel, Oliver, Sund, Malin, Małecka-Panas, Ewa, Taylor, Philip R, Tavano, Francesca, Travis, Ruth C, Thornquist, Mark, Tjønneland, Anne, Tobias, Geoffrey S, Trichopoulos, Dimitrios, Vashist, Yogesh, Vodicka, Pavel, Wactawski-Wende, Jean, Wentzensen, Nicolas, Yu, Herbert, Yu, Kai, Zeleniuch-Jacquotte, Anne, Kooperberg, Charles, Risch, Harvey A, Jacobs, Eric J, Li, Donghui, Fuchs, Charles, Hoover, Robert, Hartge, Patricia, Chanock, Stephen J, Petersen, Gloria M, Stolzenberg-Solomon, Rachael S, Wolpin, Brian M, Kraft, Peter, Klein, Alison P, Canzian, Federico, Amundadottir, Laufey T, MS MDL 1, Epi Kanker Team 1, JC onderzoeksprogramma Kanker, Cancer, Zhang, Mingfeng, Wang, Zhaoming, Obazee, Ofure, Jia, Jinping, Childs, Erica J, Hoskins, Jason, Figlioli, Gisella, Mocci, Evelina, Collins, Irene, Chung, Charles C, Hautman, Christopher, Arslan, Alan A, Beane-Freeman, Laura, Bracci, Paige M, Buring, Julie, Duell, Eric J, Gallinger, Steven, Giles, Graham G, Goodman, Gary E, Goodman, Phyllis J, Kamineni, Aruna, Kolonel, Laurence N, Kulke, Matthew H, Malats, Núria, Olson, Sara H, Sesso, Howard D, Visvanathan, Kala, White, Emily, Zheng, Wei, Abnet, Christian C, Albanes, Demetrius, Andreotti, Gabriella, Brais, Lauren, Bueno-de-Mesquita, H Bas, Basso, Daniela, Berndt, Sonja I, Boutron-Ruault, Marie-Christine, Bijlsma, Maarten F, Brenner, Hermann, Burdette, Laurie, Campa, Daniele, Caporaso, Neil E, Capurso, Gabriele, Cavestro, Giulia Martina, Cotterchio, Michelle, Costello, Eithne, Elena, Joanne, Boggi, Ugo, Gaziano, J Michael, Gazouli, Maria, Giovannucci, Edward L, Goggins, Michael, Gross, Myron, Haiman, Christopher A, Hassan, Manal, Helzlsouer, Kathy J, Hu, Nan, Hunter, David J, Iskierka-Jazdzewska, Elzbieta, Jenab, Mazda, Kaaks, Rudolf, Key, Timothy J, Khaw, Kay-Tee, Klein, Eric A, Kogevinas, Manolis, Krogh, Vittorio, Kupcinskas, Juozas, Kurtz, Robert C, Landi, Maria T, Landi, Stefano, Le Marchand, Loic, Mambrini, Andrea, Mannisto, Satu, Milne, Roger L, Neale, Rachel E, Oberg, Ann L, Panico, Salvatore, Patel, Alpa V, Peeters, Petra H M, Peters, Ulrike, Pezzilli, Raffaele, Porta, Miquel, Purdue, Mark, Quiros, J Ramón, Riboli, Elio, Rothman, Nathaniel, Scarpa, Aldo, Scelo, Ghislaine, Shu, Xiao-Ou, Silverman, Debra T, Soucek, Pavel, Strobel, Oliver, Sund, Malin, Małecka-Panas, Ewa, Taylor, Philip R, Tavano, Francesca, Travis, Ruth C, Thornquist, Mark, Tjønneland, Anne, Tobias, Geoffrey S, Trichopoulos, Dimitrios, Vashist, Yogesh, Vodicka, Pavel, Wactawski-Wende, Jean, Wentzensen, Nicolas, Yu, Herbert, Yu, Kai, Zeleniuch-Jacquotte, Anne, Kooperberg, Charles, Risch, Harvey A, Jacobs, Eric J, Li, Donghui, Fuchs, Charles, Hoover, Robert, Hartge, Patricia, Chanock, Stephen J, Petersen, Gloria M, Stolzenberg-Solomon, Rachael S, Wolpin, Brian M, Kraft, Peter, Klein, Alison P, Canzian, Federico, and Amundadottir, Laufey T

Published
2016

36. Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21

Author

Zhang, Mingfeng, primary, Wang, Zhaoming, additional, Obazee, Ofure, additional, Jia, Jinping, additional, Childs, Erica J., additional, Hoskins, Jason, additional, Figlioli, Gisella, additional, Mocci, Evelina, additional, Collins, Irene, additional, Chung, Charles C., additional, Hautman, Christopher, additional, Arslan, Alan A., additional, Beane-Freeman, Laura, additional, Bracci, Paige M., additional, Buring, Julie, additional, Duell, Eric J., additional, Gallinger, Steven, additional, Giles, Graham G., additional, Goodman, Gary E., additional, Goodman, Phyllis J., additional, Kamineni, Aruna, additional, Kolonel, Laurence N., additional, Kulke, Matthew H., additional, Malats, Núria, additional, Olson, Sara H., additional, Sesso, Howard D., additional, Visvanathan, Kala, additional, White, Emily, additional, Zheng, Wei, additional, Abnet, Christian C., additional, Albanes, Demetrius, additional, Andreotti, Gabriella, additional, Brais, Lauren, additional, Bueno-de-Mesquita, H. Bas, additional, Basso, Daniela, additional, Berndt, Sonja I., additional, Boutron-Ruault, Marie-Christine, additional, Bijlsma, Maarten F., additional, Brenner, Hermann, additional, Burdette, Laurie, additional, Campa, Daniele, additional, Caporaso, Neil E., additional, Capurso, Gabriele, additional, Cavestro, Giulia Martina, additional, Cotterchio, Michelle, additional, Costello, Eithne, additional, Elena, Joanne, additional, Boggi, Ugo, additional, Gaziano, J. Michael, additional, Gazouli, Maria, additional, Giovannucci, Edward L., additional, Goggins, Michael, additional, Gross, Myron, additional, Haiman, Christopher A., additional, Hassan, Manal, additional, Helzlsouer, Kathy J., additional, Hu, Nan, additional, Hunter, David J., additional, Iskierka-Jazdzewska, Elzbieta, additional, Jenab, Mazda, additional, Kaaks, Rudolf, additional, Key, Timothy J., additional, Khaw, Kay-Tee, additional, Klein, Eric A., additional, Kogevinas, Manolis, additional, Krogh, Vittorio, additional, Kupcinskas, Juozas, additional, Kurtz, Robert C., additional, Landi, Maria T., additional, Landi, Stefano, additional, Le Marchand, Loic, additional, Mambrini, Andrea, additional, Mannisto, Satu, additional, Milne, Roger L., additional, Neale, Rachel E., additional, Oberg, Ann L., additional, Panico, Salvatore, additional, Patel, Alpa V., additional, Peeters, Petra H. M., additional, Peters, Ulrike, additional, Pezzilli, Raffaele, additional, Porta, Miquel, additional, Purdue, Mark, additional, Quiros, J. Ramón, additional, Riboli, Elio, additional, Rothman, Nathaniel, additional, Scarpa, Aldo, additional, Scelo, Ghislaine, additional, Shu, Xiao-Ou, additional, Silverman, Debra T., additional, Soucek, Pavel, additional, Strobel, Oliver, additional, Sund, Malin, additional, Małecka-Panas, Ewa, additional, Taylor, Philip R., additional, Tavano, Francesca, additional, Travis, Ruth C., additional, Thornquist, Mark, additional, Tjønneland, Anne, additional, Tobias, Geoffrey S., additional, Trichopoulos, Dimitrios, additional, Vashist, Yogesh, additional, Vodicka, Pavel, additional, Wactawski-Wende, Jean, additional, Wentzensen, Nicolas, additional, Yu, Herbert, additional, Yu, Kai, additional, Zeleniuch-Jacquotte, Anne, additional, Kooperberg, Charles, additional, Risch, Harvey A., additional, Jacobs, Eric J., additional, Li, Donghui, additional, Fuchs, Charles, additional, Hoover, Robert, additional, Hartge, Patricia, additional, Chanock, Stephen J., additional, Petersen, Gloria M., additional, Stolzenberg-Solomon, Rachael S., additional, Wolpin, Brian M., additional, Kraft, Peter, additional, Klein, Alison P., additional, Canzian, Federico, additional, and Amundadottir, Laufey T., additional

Published
2016
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37. Novel pancreatic cancer susceptibility loci discovered through genome-wide association studies

Author

Stolzenberg-Solomon, Rachael, Wolpin, Brian, Klein, Alison P., Amundadottir, Laufey T., Canzian, Federico, Campa, Daniele, Obazee, Ofure, Rizzato, Cosmeri, Gazouli, Maria, Cavestro, Giulia Martina, Scarpa, Aldo, Moz, Stefania, Pezzilli, Raffaele, Mambrini, Andrea, Boggi, Ugo, Capurso, Gabriele, Archibugi, Livia, Bambi, Franco, Andriulli, Angelo, Soucek, Pavel, Vodicka, Pavel, Mohelnikova-Duchonova, Beatrice, Lovecek, Martin, Hackert, Thilo, Neoptolemos, John P., Strobel, Oliver, Vashist, Yogesh K., Izbicki, Jakob R., Kaaks, Rudolf, Brenner, Hermann, Hegyi, Peter, Busch, Olivier, Bueno-de-Mesquita, H. Bas, Peeters, Petra H.M., Malecka-Panas, Ewa, Jamroziak, Krzysztof, Kupcinskas, Juozas, Costello, Eithne, Khaw, Kay-Tee, and Key, Timothy J.

Published
2018
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38. Exome sequencing identifies germline variants in DIS3in familial multiple myeloma

Author

Pertesi, Maroulio, Vallée, Maxime, Wei, Xiaomu, Revuelta, Maria V., Galia, Perrine, Demangel, Delphine, Oliver, Javier, Foll, Matthieu, Chen, Siwei, Perrial, Emeline, Garderet, Laurent, Corre, Jill, Leleu, Xavier, Boyle, Eileen M., Decaux, Olivier, Rodon, Philippe, Kolb, Brigitte, Slama, Borhane, Mineur, Philippe, Voog, Eric, Le Bris, Catherine, Fontan, Jean, Maigre, Michel, Beaumont, Marie, Azais, Isabelle, Sobol, Hagay, Vignon, Marguerite, Royer, Bruno, Perrot, Aurore, Fuzibet, Jean-Gabriel, Dorvaux, Véronique, Anglaret, Bruno, Cony-Makhoul, Pascale, Berthou, Christian, Desquesnes, Florence, Pegourie, Brigitte, Leyvraz, Serge, Mosser, Laurent, Frenkiel, Nicole, Augeul-Meunier, Karine, Leduc, Isabelle, Leyronnas, Cécile, Voillat, Laurent, Casassus, Philippe, Mathiot, Claire, Cheron, Nathalie, Paubelle, Etienne, Moreau, Philippe, Bignon, Yves–Jean, Joly, Bertrand, Bourquard, Pascal, Caillot, Denis, Naman, Hervé, Rigaudeau, Sophie, Marit, Gérald, Macro, Margaret, Lambrecht, Isabelle, Cliquennois, Manuel, Vincent, Laure, Helias, Philippe, Avet-Loiseau, Hervé, Moreno, Victor, Reis, Rui Manuel, Varkonyi, Judit, Kruszewski, Marcin, Vangsted, Annette Juul, Jurczyszyn, Artur, Zaucha, Jan Maciej, Sainz, Juan, Krawczyk-Kulis, Malgorzata, Wątek, Marzena, Pelosini, Matteo, Iskierka-Jażdżewska, Elzbieta, Grząśko, Norbert, Martinez-Lopez, Joaquin, Jerez, Andrés, Campa, Daniele, Buda, Gabriele, Lesueur, Fabienne, Dudziński, Marek, García-Sanz, Ramón, Nagler, Arnon, Rymko, Marcin, Jamroziak, Krzysztof, Butrym, Aleksandra, Canzian, Federico, Obazee, Ofure, Nilsson, Björn, Klein, Robert J., Lipkin, Steven M., McKay, James D., and Dumontet, Charles

Published
2019
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39. Abstract 1337: The UGT1A6_19_GG genotype is associated with increased breast cancer risk based on a two-stage study.

Author

Obazee, Ofure M., primary, Justenhoven, Christina, additional, Winter, Stefan, additional, Rabstein, Sylvia, additional, Lotz, Anne, additional, Harth, Volker, additional, Pesch, Beate, additional, Brüning, Thomas, additional, Baisch, Christian, additional, Hartikainen, Jaana M., additional, Mannermaa, Arto, additional, Winqvist, Robert, additional, Fasching, Peter, additional, Hall, Per, additional, Chang-Claude, Jenny, additional, Hamann, Ute, additional, Ko, Yon-Dschun, additional, and Brauch, Hiltrud, additional

Published
2013
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40. The UGT1A6_19_GG genotype is a breast cancer risk factor

Author

Justenhoven, Christina, primary, Obazee, Ofure, additional, Winter, Stefan, additional, Rabstein, Sylvia, additional, Lotz, Anne, additional, Harth, Volker, additional, Pesch, Beate, additional, Brüning, Thomas, additional, Baisch, Christian, additional, Hartikainen, Jaana M., additional, Mannermaa, Arto, additional, Kosma, Veli-Matti, additional, Kataja, Vesa, additional, Winqvist, Robert, additional, Pylkäs, Katri, additional, Jukkola-Vuorinen, Arja, additional, Grip, Mervi, additional, Fasching, Peter A., additional, Beckmann, Matthias, additional, Ekici, Arif B., additional, Hein, Alexander, additional, Hall, Per, additional, Li, Jingmei, additional, Chang-Claude, Jenny, additional, Flesch-Janys, Dieter, additional, Seibold, Petra, additional, Rudolph, Anja, additional, Hamann, Ute, additional, Ko, Yon-Dschun, additional, and Brauch, Hiltrud, additional

Published
2013
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41. The postmenopausal hormone replacement therapy-related breast cancer risk is decreased in women carrying the CYP2C19*17 variant

Author

Justenhoven, Christina, primary, Obazee, Ofure, additional, Winter, Stefan, additional, Couch, Fergus J., additional, Olson, Janet E., additional, Hall, Per, additional, Hannelius, Ulf, additional, Li, Jingmei, additional, Humphreys, Keith, additional, Severi, Gianluca, additional, Giles, Graham, additional, Southey, Melissa, additional, Baglietto, Laura, additional, Fasching, Peter A., additional, Beckmann, Matthias W., additional, Ekici, Arif B., additional, Hamann, Ute, additional, Baisch, Christian, additional, Harth, Volker, additional, Rabstein, Sylvia, additional, Lotz, Anne, additional, Pesch, Beate, additional, Brüning, Thomas, additional, Ko, Yon-Dschun, additional, and Brauch, Hiltrud, additional

Published
2011
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42. Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer

Author

Klein, Alison P, Wolpin, Brian M, Risch, Harvey A, Stolzenberg-Solomon, Rachael Z, Mocci, Evelina, Zhang, Mingfeng, Canzian, Federico, Childs, Erica J, Hoskins, Jason W, Jermusyk, Ashley, Zhong, Jun, Chen, Fei, Albanes, Demetrius, Andreotti, Gabriella, Arslan, Alan A, Babic, Ana, Bamlet, William R, Beane-Freeman, Laura, Berndt, Sonja I, Blackford, Amanda, Borges, Michael, Borgida, Ayelet, Bracci, Paige M, Brais, Lauren, Brennan, Paul, Brenner, Hermann, Bueno-De-Mesquita, Bas, Buring, Julie, Campa, Daniele, Capurso, Gabriele, Cavestro, Giulia Martina, Chaffee, Kari G, Chung, Charles C, Cleary, Sean, Cotterchio, Michelle, Dijk, Frederike, Duell, Eric J, Foretova, Lenka, Fuchs, Charles, Funel, Niccola, Gallinger, Steven, M Gaziano, J Michael, Gazouli, Maria, Giles, Graham G, Giovannucci, Edward, Goggins, Michael, Goodman, Gary E, Goodman, Phyllis J, Hackert, Thilo, Haiman, Christopher, Hartge, Patricia, Hasan, Manal, Hegyi, Peter, Helzlsouer, Kathy J, Herman, Joseph, Holcatova, Ivana, Holly, Elizabeth A, Hoover, Robert, Hung, Rayjean J, Jacobs, Eric J, Jamroziak, Krzysztof, Janout, Vladimir, Kaaks, Rudolf, Khaw, Kay-Tee, Klein, Eric A, Kogevinas, Manolis, Kooperberg, Charles, Kulke, Matthew H, Kupcinskas, Juozas, Kurtz, Robert J, Laheru, Daniel, Landi, Stefano, Lawlor, Rita T, Lee, I-Min, LeMarchand, Loic, Lu, Lingeng, Malats, Núria, Mambrini, Andrea, Mannisto, Satu, Milne, Roger L, Mohelníková-Duchoňová, Beatrice, Neale, Rachel E, Neoptolemos, John P, Oberg, Ann L, Olson, Sara H, Orlow, Irene, Pasquali, Claudio, Patel, Alpa V, Peters, Ulrike, Pezzilli, Raffaele, Porta, Miquel, Real, Francisco X, Rothman, Nathaniel, Scelo, Ghislaine, Sesso, Howard D, Severi, Gianluca, Shu, Xiao-Ou, Silverman, Debra, Smith, Jill P, Soucek, Pavel, Sund, Malin, Talar-Wojnarowska, Renata, Tavano, Francesca, Thornquist, Mark D, Tobias, Geoffrey S, Van Den Eeden, Stephen K, Vashist, Yogesh, Visvanathan, Kala, Vodicka, Pavel, Wactawski-Wende, Jean, Wang, Zhaoming, Wentzensen, Nicolas, White, Emily, Yu, Herbert, Yu, Kai, Zeleniuch-Jacquotte, Anne, Zheng, Wei, Kraft, Peter, Li, Donghui, Chanock, Stephen, Obazee, Ofure, Petersen, Gloria M, and Amundadottir, Laufey T

Subjects
Intracellular Signaling Peptides and Proteins, Proteins, Polymorphism, Single Nucleotide, 3. Good health, Pancreatic Neoplasms, Repressor Proteins, Hepatocyte Nuclear Factor 4, Tensins, Databases, Genetic, Humans, Intercellular Signaling Peptides and Proteins, Genetic Predisposition to Disease, Carcinoma, Pancreatic Ductal, Genome-Wide Association Study, Hepatocyte Nuclear Factor 1-beta
Abstract

In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 × 10-8). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 × 10-14), rs2941471 at 8q21.11 (HNF4G, P = 6.60 × 10-10), rs4795218 at 17q12 (HNF1B, P = 1.32 × 10-8), and rs1517037 at 18q21.32 (GRP, P = 3.28 × 10-8). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene.

43. Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21

Author

Zhang, Mingfeng, Wang, Zhaoming, Obazee, Ofure, Jia, Jinping, Childs, Erica J, Hoskins, Jason, Figlioli, Gisella, Mocci, Evelina, Collins, Irene, Chung, Charles C, Hautman, Christopher, Arslan, Alan A, Beane-Freeman, Laura, Bracci, Paige M, Buring, Julie, Duell, Eric J, Gallinger, Steven, Giles, Graham G, Goodman, Gary E, Goodman, Phyllis J, Kamineni, Aruna, Kolonel, Laurence N, Kulke, Matthew H, Malats, Núria, Olson, Sara H, Sesso, Howard D, Visvanathan, Kala, White, Emily, Zheng, Wei, Abnet, Christian C, Albanes, Demetrius, Andreotti, Gabriella, Brais, Lauren, Bueno-De-Mesquita, H Bas, Basso, Daniela, Berndt, Sonja I, Boutron-Ruault, Marie-Christine, Bijlsma, Maarten F, Brenner, Hermann, Burdette, Laurie, Campa, Daniele, Caporaso, Neil E, Capurso, Gabriele, Cavestro, Giulia Martina, Cotterchio, Michelle, Costello, Eithne, Elena, Joanne, Boggi, Ugo, Gaziano, J Michael, Gazouli, Maria, Giovannucci, Edward L, Goggins, Michael, Gross, Myron, Haiman, Christopher A, Hassan, Manal, Helzlsouer, Kathy J, Hu, Nan, Hunter, David J, Iskierka-Jazdzewska, Elzbieta, Jenab, Mazda, Kaaks, Rudolf, Key, Timothy J, Khaw, Kay-Tee, Klein, Eric A, Kogevinas, Manolis, Krogh, Vittorio, Kupcinskas, Juozas, Kurtz, Robert C, Landi, Maria T, Landi, Stefano, Le Marchand, Loic, Mambrini, Andrea, Mannisto, Satu, Milne, Roger L, Neale, Rachel E, Oberg, Ann L, Panico, Salvatore, Patel, Alpa V, Peeters, Petra HM, Peters, Ulrike, Pezzilli, Raffaele, Porta, Miquel, Purdue, Mark, Quiros, J Ramón, Riboli, Elio, Rothman, Nathaniel, Scarpa, Aldo, Scelo, Ghislaine, Shu, Xiao-Ou, Silverman, Debra T, Soucek, Pavel, Strobel, Oliver, Sund, Malin, Małecka-Panas, Ewa, Taylor, Philip R, Tavano, Francesca, Travis, Ruth C, Thornquist, Mark, Tjønneland, Anne, Tobias, Geoffrey S, Trichopoulos, Dimitrios, Vashist, Yogesh, Vodicka, Pavel, Wactawski-Wende, Jean, Wentzensen, Nicolas, Yu, Herbert, Yu, Kai, Zeleniuch-Jacquotte, Anne, Kooperberg, Charles, Risch, Harvey A, Jacobs, Eric J, Li, Donghui, Fuchs, Charles, Hoover, Robert, Hartge, Patricia, Chanock, Stephen J, Petersen, Gloria M, Stolzenberg-Solomon, Rachael S, Wolpin, Brian M, Kraft, Peter, Klein, Alison P, Canzian, Federico, and Amundadottir, Laufey T

Subjects
Genotype, NR5A2, pancreatic cancer, Datasets as Topic, imputation, Polymorphism, Single Nucleotide, 3. Good health, Pancreatic Neoplasms, fine-mapping, Chromosomes, Human, Pair 1, GWAS, Chromosomes, Human, Pair 5, Humans, Genetic Predisposition to Disease, Chromosomes, Human, Pair 8, Genome-Wide Association Study
Abstract

Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10 -15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10 -9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10 -8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 ( NR5A2), chr8q24.21 ( MYC) and chr5p15.33 ( CLPTM1L- TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal ( n = 10) and tumor ( n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10 -8). This finding was validated in a second set of paired ( n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10 -4-2.0x10 -3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology.

44. Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21

Author

Anne Tjønneland, Jason W. Hoskins, Kala Visvanathan, Yogesh K. Vashist, Dimitrios Trichopoulos, Matthew H. Kulke, Ruth C. Travis, Charles S. Fuchs, Herbert Yu, Kai Yu, Phyllis J. Goodman, Michael Goggins, Jean Wactawski-Wende, Laurie Burdette, Joanne W. Elena, Andrea Mambrini, Petra H.M. Peeters, H. Bas Bueno-de-Mesquita, Maria Teresa Landi, Ulrike Peters, Mingfeng Zhang, Laurence N. Kolonel, Hermann Brenner, Elżbieta Iskierka-Jażdżewska, Robert C. Kurtz, Stephen J. Chanock, Marie-Christine Boutron-Ruault, Ann L. Oberg, Elio Riboli, Maarten F. Bijlsma, Eric J. Jacobs, Manolis Kogevinas, Evelina Mocci, Steven Gallinger, Jinping Jia, Mark P. Purdue, Raffaele Pezzilli, Harvey A. Risch, Demetrius Albanes, Irene Collins, Maria Gazouli, Michelle Cotterchio, Oliver Strobel, Erica J. Childs, Charles C. Chung, Geoffrey S. Tobias, J. Ramón Quirós, Núria Malats, Robert N. Hoover, Pavel Vodicka, Brian M. Wolpin, Ugo Boggi, Patricia Hartge, Gloria M. Petersen, Peter Kraft, Christopher Hautman, Gary E. Goodman, Manal Hassan, Donghui Li, Howard D. Sesso, Malin Sund, Julie E. Buring, Loic Le Marchand, Wei Zheng, Xiao-Ou Shu, Ewa Małecka-Panas, Pavel Soucek, Salvatore Panico, Nicolas Wentzensen, Graham G. Giles, Alpa V. Patel, Daniele Campa, Myron D. Gross, Ghislaine Scelo, J. Michael Gaziano, Juozas Kupcinskas, Debra T. Silverman, Laufey T. Amundadottir, Rachael S. Stolzenberg-Solomon, Neil E. Caporaso, Mazda Jenab, Sara H. Olson, Stefano Landi, Giulia Martina Cavestro, Aruna Kamineni, Laura Beane-Freeman, Roger L. Milne, Rachel E. Neale, Aldo Scarpa, Kathy J. Helzlsouer, Miquel Porta, Emily White, Eric J. Duell, Paige M. Bracci, Nan Hu, Federico Canzian, Eric A. Klein, Gabriele Capurso, Anne Zeleniuch-Jacquotte, Eithne Costello, David J. Hunter, Rudolf Kaaks, Sonja I. Berndt, Kay-Tee Khaw, Nathaniel Rothman, Christian C. Abnet, Francesca Tavano, Christopher A. Haiman, Zhaoming Wang, Ofure Obazee, Alan A. Arslan, Edward Giovannucci, Alison P. Klein, Daniela Basso, Charles Kooperberg, Philip R. Taylor, Satu Männistö, Timothy J. Key, Mark D. Thornquist, Gabriella Andreotti, Lauren K. Brais, Gisella Figlioli, Vittorio Krogh, University Medical Center Utrecht, Imperial College Trust, Cancer Research UK, Medical Research Council UK (MRC), National Institute for Health Research (NIHR), Cancer Research UK (Reino Unido), Medical Research Council (Reino Unido), National Institute for Health Research (Reino Unido), Zhang, Mingfeng, Wang, Zhaoming, Obazee, Ofure, Jia, Jinping, Childs, Erica J, Hoskins, Jason, Figlioli, Gisella, Mocci, Evelina, Collins, Irene, Chung, Charles C, Hautman, Christopher, Arslan, Alan A, Beane Freeman, Laura, Bracci, Paige M, Buring, Julie, Duell, Eric J, Gallinger, Steven, Giles, Graham G, Goodman, Gary E, Goodman, Phyllis J, Kamineni, Aruna, Kolonel, Laurence N, Kulke, Matthew H, Malats, Núria, Olson, Sara H, Sesso, Howard D, Visvanathan, Kala, White, Emily, Zheng, Wei, Abnet, Christian C, Albanes, Demetriu, Andreotti, Gabriella, Brais, Lauren, Bueno de Mesquita, H. Ba, Basso, Daniela, Berndt, Sonja I, Boutron Ruault, Marie Christine, Bijlsma, Maarten F, Brenner, Hermann, Burdette, Laurie, Campa, Daniele, Caporaso, Neil E, Capurso, Gabriele, Cavestro, Giulia Martina, Cotterchio, Michelle, Costello, Eithne, Elena, Joanne, Boggi, Ugo, Gaziano, J. Michael, Gazouli, Maria, Giovannucci, Edward L, Goggins, Michael, Gross, Myron, Haiman, Christopher A, Hassan, Manal, Helzlsouer, Kathy J, Hu, Nan, Hunter, David J, Iskierka Jazdzewska, Elzbieta, Jenab, Mazda, Kaaks, Rudolf, Key, Timothy J, Khaw, Kay Tee, Klein, Eric A, Kogevinas, Manoli, Krogh, Vittorio, Kupcinskas, Juoza, Kurtz, Robert C, Landi, Maria T, Landi, Stefano, Le Marchand, Loic, Mambrini, Andrea, Mannisto, Satu, Milne, Roger L, Neale, Rachel E, Oberg, Ann L, Panico, Salvatore, Patel, Alpa V, Peeters, Petra H. M, Peters, Ulrike, Pezzilli, Raffaele, Porta, Miquel, Purdue, Mark, Quiros, J. Ramón, Riboli, Elio, Rothman, Nathaniel, Scarpa, Aldo, Scelo, Ghislaine, Shu, Xiao Ou, Silverman, Debra T, Soucek, Pavel, Strobel, Oliver, Sund, Malin, Małecka Panas, Ewa, Taylor, Philip R, Tavano, Francesca, Travis, Ruth C, Thornquist, Mark, Tjønneland, Anne, Tobias, Geoffrey S, Trichopoulos, Dimitrio, Vashist, Yogesh, Vodicka, Pavel, Wactawski Wende, Jean, Wentzensen, Nicola, Yu, Herbert, Yu, Kai, Zeleniuch Jacquotte, Anne, Kooperberg, Charle, Risch, Harvey A, Jacobs, Eric J, Li, Donghui, Fuchs, Charle, Hoover, Robert, Hartge, Patricia, Chanock, Stephen J, Petersen, Gloria M, Stolzenberg Solomon, Rachael S, Wolpin, Brian M, Kraft, Peter, Klein, Alison P, Canzian, Federico, Amundadottir, Laufey T., Khaw, Kay-Tee [0000-0002-8802-2903], Apollo - University of Cambridge Repository, CCA -Cancer Center Amsterdam, Center of Experimental and Molecular Medicine, Radiotherapy, Zhang, M, Wang, Z, Obazee, O, Jia, J, Childs, Ej, Hoskins, J, Figlioli, G, Mocci, E, Collins, I, Chung, Cc, Hautman, C, Arslan, Aa, Beane Freeman, L, Bracci, Pm, Buring, J, Duell, Ej, Gallinger, S, Giles, Gg, Goodman, Ge, Goodman, Pj, Kamineni, A, Kolonel, Ln, Kulke, Mh, Malats, N, Olson, Sh, Sesso, Hd, Visvanathan, K, White, E, Zheng, W, Abnet, Cc, Albanes, D, Andreotti, G, Brais, L, Bueno de Mesquita, Hb, Basso, D, Berndt, Si, Boutron Ruault, Mc, Bijlsma, Mf, Brenner, H, Burdette, L, Campa, D, Caporaso, Ne, Capurso, G, Cavestro, GIULIA MARTINA, Cotterchio, M, Costello, E, Elena, J, Boggi, U, Gaziano, Jm, Gazouli, M, Giovannucci, El, Goggins, M, Gross, M, Haiman, Ca, Hassan, M, Helzlsouer, Kj, Hu, N, Hunter, Dj, Iskierka Jazdzewska, E, Jenab, M, Kaaks, R, Key, Tj, Khaw, Kt, Klein, Ea, Kogevinas, M, Krogh, V, Kupcinskas, J, Kurtz, Rc, Landi, Mt, Landi, S, Le Marchand, L, Mambrini, A, Mannisto, S, Milne, Rl, Neale, Re, Oberg, Al, Panico, S, Patel, Av, Peeters, Ph, Peters, U, Pezzilli, R, Porta, M, Purdue, M, Quiros, Jr, Riboli, E, Rothman, N, Scarpa, A, Scelo, G, Shu, Xo, Silverman, Dt, Soucek, P, Strobel, O, Sund, M, Małecka Panas, E, Taylor, Pr, Tavano, F, Travis, Rc, Thornquist, M, Tjønneland, A, Tobias, G, Trichopoulos, D, Vashist, Y, Vodicka, P, Wactawski Wende, J, Wentzensen, N, Yu, H, Yu, K, Zeleniuch Jacquotte, A, Kooperberg, C, Risch, Ha, Jacobs, Ej, Li, D, Fuchs, C, Hoover, R, Hartge, P, Chanock, Sj, Petersen, Gm, Stolzenberg Solomon, R, Wolpin, Bm, Kraft, P, Klein, Ap, Canzian, F, and Amundadottir, L. T.

Subjects
0301 basic medicine, Candidate gene, Pancreatic disease, GENETIC SUSCEPTIBILITY, pancreatic cancer, Datasets as Topic, Genome-wide association study, imputation, TRET, 0302 clinical medicine, Fine-mapping, GWAS, Imputation, NR5A2, Pancreatic cancer, Oncology, Genotype, Genetics, 3. Good health, fine-mapping, Chromosomes, Human, Pair 1, 030220 oncology & carcinogenesis, Chromosomes, Human, Pair 5, Chromosomes, Human, Pair 8, 616.37-006.6 [udc], BLADDER-CANCER, Single-nucleotide polymorphism, GENOTYPE IMPUTATION, BREAST, Polymorphism, Single Nucleotide, 03 medical and health sciences, Journal Article, medicine, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Pàncrees -- Càncer, Cancer och onkologi, LONG-RANGE INTERACTION, business.industry, medicine.disease, Pancreatic neoplasms, genetics, Polymorphism, single nucleotide, RISK LOCI, Fold change, COMMON VARIANT, Cromosomes, Pancreatic Neoplasms, 030104 developmental biology, Cancer and Oncology, business, Imputation (genetics), LRH-1, Priority Research Paper, Genome-Wide Association Study
Abstract

Altres ajuts: The authors acknowledge the contribution of the staff of the Cancer Genomics Research Laboratory (CGR) at the National Cancer Institute, NIH, for their help throughout the project. This work was supported by the Intramural Research Program of the US National Institutes of Health (NIH), National Cancer Institute. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. Additional acknowledgements for individual participating studies are listed in the Supplemental Materials. Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88×10 −15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22×10 −9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70×10 −8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 (NR5A2), chr8q24.21 (MYC) and chr5p15.33 (CLPTM1L - TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal (n = 10) and tumor (n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7×10 −8). This finding was validated in a second set of paired (n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5×10 −4 -2.0×10 −3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology.

Published
2016

45. Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer

Author

Christopher A. Haiman, Herbert Yu, Lauren K. Brais, Gabriele Capurso, Eric J. Duell, Michelle Cotterchio, Núria Malats, Beatrice Mohelníková-Duchoňová, Claudio Pasquali, Gary E. Goodman, Giulia Martina Cavestro, Kala Visvanathan, Sean P. Cleary, Jill P. Smith, Jean Wactawski-Wende, Rita T. Lawlor, Gianluca Severi, J. Michael Gaziano, Kathy J. Helzlsouer, Charles C. Chung, Harvey A. Risch, Stephen K. Van Den Eeden, Elizabeth A. Holly, Bas Bueno-de-Mesquita, Patricia Hartge, Fei Chen, Mark D. Thornquist, Hermann Brenner, Ulrike Peters, Ghislaine Scelo, Steven Gallinger, Sonja I. Berndt, Howard D. Sesso, Lenka Foretova, Laufey T. Amundadottir, Mingfeng Zhang, Federico Canzian, Rudolf Kaaks, Stephen J. Chanock, Nicolas Wentzensen, Ann L. Oberg, Eric J. Jacobs, Peter Kraft, Rayjean J. Hung, Evelina Mocci, Maria Gazouli, Francesca Tavano, Michael Borges, Zhaoming Wang, Alan A. Arslan, Wei Zheng, Ayelet Borgida, Paige M. Bracci, Jason W. Hoskins, William R. Bamlet, Juozas Kupcinskas, Joseph M. Herman, Demetrius Albanes, Charles S. Fuchs, Nathaniel Rothman, Niccola Funel, Pavel Soucek, Edward Giovannucci, Paul Brennan, Thilo Hackert, Jun Zhong, Manolis Kogevinas, Robert N. Hoover, Michael Goggins, Amanda L. Blackford, Robert J. Kurtz, Malin Sund, Roger L. Milne, Stefano Landi, Francisco X. Real, Emily White, Miquel Porta, Ivana Holcatova, Kari G. Chaffee, Vladimir Janout, Charles Kooperberg, Péter Hegyi, Frederike Dijk, Yogesh K. Vashist, Andrea Mambrini, Matthew H. Kulke, I. Min Lee, Kai Yu, Alison P. Klein, Phyllis J. Goodman, Donghui Li, Julie E. Buring, Debra T. Silverman, Ana Babic, John P. Neoptolemos, Erica J. Childs, Alpa V. Patel, Sara H. Olson, Brian M. Wolpin, Krzysztof Jamroziak, Gloria M. Petersen, Xiao-Ou Shu, Renata Talar-Wojnarowska, Rachel E. Neale, Daniel A. Laheru, Kay-Tee Khaw, Eric A. Klein, Ashley Jermusyk, Graham G. Giles, Daniele Campa, Laura Beane-Freeman, Rachael Z. Stolzenberg-Solomon, Raffaele Pezzilli, Geoffrey S. Tobias, Pavel Vodicka, Irene Orlow, Anne Zeleniuch-Jacquotte, Ofure Obazee, Satu Männistö, Lingeng Lu, Manal Hasan, Loic LeMarchand, Gabriella Andreotti, CCA - Cancer biology and immunology, Pathology, Lung Cancer Research Foundation, Sol Goldman Pancreas Cancer Research Center, Geoffrey Beene Foundation, Arnold and Arlene Goldstein Family Foundation, National Health and Medical Research Council (Australia), Czech Science Foundation, Joan Rombauer Pancreatic Cancer Foundation, NIH - National Cancer Institute (NCI) (Estados Unidos), Instituto de Salud Carlos III, Ministerio de Ciencia y Tecnología (España), Red Temática de Investigación Cooperativa en Cáncer (España), Centro de Investigación Biomédica en Red - CIBERESP (Epidemiología y Salud Pública), Mocci, Evelina [0000-0002-7101-9556], Canzian, Federico [0000-0002-4261-4583], Chaffee, Kari G [0000-0002-7313-1875], Dijk, Frederike [0000-0003-3970-6601], Gazouli, Maria [0000-0002-3295-6811], Jacobs, Eric J [0000-0002-8458-7659], Klein, Eric A [0000-0002-1783-0698], Lu, Lingeng [0000-0001-9871-0809], Malats, Núria [0000-0003-2538-3784], Milne, Roger L [0000-0001-5764-7268], Neoptolemos, John P [0000-0002-6201-7399], Oberg, Ann L [0000-0003-2539-9807], Pezzilli, Raffaele [0000-0001-9827-7451], Porta, Miquel [0000-0003-1684-7428], Real, Francisco X [0000-0001-9501-498X], Sund, Malin [0000-0002-7516-9543], Tobias, Geoffrey S [0000-0002-2878-8253], Van Den Eeden, Stephen K [0000-0002-5599-8387], Yu, Herbert [0000-0003-3950-4815], Zheng, Wei [0000-0003-1226-070X], Obazee, Ofure [0000-0001-8791-5008], Amundadottir, Laufey T [0000-0003-1859-8971], Apollo - University of Cambridge Repository, Klein, Alison P., Wolpin, Brian M., Risch, Harvey A., Stolzenberg-Solomon, Rachael Z., Mocci, Evelina, Zhang, Mingfeng, Canzian, Federico, Childs, Erica J., Hoskins, Jason W., Jermusyk, Ashley, Zhong, Jun, Chen, Fei, Albanes, Demetriu, Andreotti, Gabriella, Arslan, Alan A., Babic, Ana, Bamlet, William R., Beane-Freeman, Laura, Berndt, Sonja I., Blackford, Amanda, Borges, Michael, Borgida, Ayelet, Bracci, Paige M., Brais, Lauren, Brennan, Paul, Brenner, Hermann, Bueno-De-Mesquita, Ba, Buring, Julie, Campa, Daniele, Capurso, Gabriele, Cavestro, Giulia Martina, Chaffee, Kari G., Chung, Charles C., Cleary, Sean, Cotterchio, Michelle, Dijk, Frederike, Duell, Eric J., Foretova, Lenka, Fuchs, Charle, Funel, Niccola, Gallinger, Steven, Gaziano, J. Michael M., Gazouli, Maria, Giles, Graham G., Giovannucci, Edward, Goggins, Michael, Goodman, Gary E., Goodman, Phyllis J., Hackert, Thilo, Haiman, Christopher, Hartge, Patricia, Hasan, Manal, Hegyi, Peter, Helzlsouer, Kathy J., Herman, Joseph, Holcatova, Ivana, Holly, Elizabeth A., Hoover, Robert, Hung, Rayjean J., Jacobs, Eric J., Jamroziak, Krzysztof, Janout, Vladimir, Kaaks, Rudolf, Khaw, Kay-Tee, Klein, Eric A., Kogevinas, Manoli, Kooperberg, Charle, Kulke, Matthew H., Kupcinskas, Juoza, Kurtz, Robert J., Laheru, Daniel, Landi, Stefano, Lawlor, Rita T., Lee, I. -Min, Lemarchand, Loic, Lu, Lingeng, Malats, Núria, Mambrini, Andrea, Mannisto, Satu, Milne, Roger L., Mohelníková-Duchoňová, Beatrice, Neale, Rachel E., Neoptolemos, John P., Oberg, Ann L., Olson, Sara H., Orlow, Irene, Pasquali, Claudio, Patel, Alpa V., Peters, Ulrike, Pezzilli, Raffaele, Porta, Miquel, Real, Francisco X., Rothman, Nathaniel, Scelo, Ghislaine, Sesso, Howard D., Severi, Gianluca, Shu, Xiao-Ou, Silverman, Debra, Smith, Jill P., Soucek, Pavel, Sund, Malin, Talar-Wojnarowska, Renata, Tavano, Francesca, Thornquist, Mark D., Tobias, Geoffrey S., Van Den Eeden, Stephen K., Vashist, Yogesh, Visvanathan, Kala, Vodicka, Pavel, Wactawski-Wende, Jean, Wang, Zhaoming, Wentzensen, Nicola, White, Emily, Yu, Herbert, Yu, Kai, Zeleniuch-Jacquotte, Anne, Zheng, Wei, Kraft, Peter, Li, Donghui, Chanock, Stephen, Obazee, Ofure, Petersen, Gloria M., and Amundadottir, Laufey T.

Subjects
0301 basic medicine, Oncology, Genetics and Molecular Biology (all), Pancreatic disease, Chemistry(all), General Physics and Astronomy, Genome-wide association study, Disease, Biochemistry, DISEASE, Tensins, Databases, Genetic, IMPUTATION, 03.02. Klinikai orvostan, lcsh:Science, Càncer, Pancreas cancer, GENE-EXPRESSION, Cancer, RISK, Multidisciplinary, Chemistry (all), Pancreatic Neoplasm, Intracellular Signaling Peptides and Proteins, HNF1B, 3. Good health, TRANSCRIPTION FACTORS, Hepatocyte Nuclear Factor 4, Intercellular Signaling Peptides and Proteins, Human, Carcinoma, Pancreatic Ductal, medicine.medical_specialty, Science, Physics and Astronomy(all), Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Physics and Astronomy (all), Cancer epidemiology, Pancreatic cancer, Internal medicine, medicine, Carcinoma, Humans, Genetic Predisposition to Disease, Allele, Càncer de pàncrees, Hepatocyte Nuclear Factor 1-beta, Cancer och onkologi, Biochemistry, Genetics and Molecular Biology (all), business.industry, Biochemistry, Genetics and Molecular Biology(all), Protein, Proteins, ADENOCARCINOMA, General Chemistry, Repressor Protein, medicine.disease, Pancreatic Neoplasms, Repressor Proteins, BODY-MASS INDEX, 030104 developmental biology, Tensin, Cancer and Oncology, Expression quantitative trait loci, lcsh:Q, business, ASSOCIATION ANALYSES, Genetics and Molecular Biology(all), Genome-Wide Association Study
Abstract

In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 × 10−8). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 × 10−14), rs2941471 at 8q21.11 (HNF4G, P = 6.60 × 10−10), rs4795218 at 17q12 (HNF1B, P = 1.32 × 10−8), and rs1517037 at 18q21.32 (GRP, P = 3.28 × 10−8). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene., Genetic variants associated with susceptibility to pancreatic cancer have been identified using genome wide association studies (GWAS). Here, the authors combine data from over 9000 patients and perform a meta-analysis to identify five novel loci linked to pancreatic cancer.

46. A Transcriptome-Wide Association Study Identifies Novel Candidate Susceptibility Genes for Pancreatic Cancer.

Author

Zhong J, Jermusyk A, Wu L, Hoskins JW, Collins I, Mocci E, Zhang M, Song L, Chung CC, Zhang T, Xiao W, Albanes D, Andreotti G, Arslan AA, Babic A, Bamlet WR, Beane-Freeman L, Berndt S, Borgida A, Bracci PM, Brais L, Brennan P, Bueno-de-Mesquita B, Buring J, Canzian F, Childs EJ, Cotterchio M, Du M, Duell EJ, Fuchs C, Gallinger S, Gaziano JM, Giles GG, Giovannucci E, Goggins M, Goodman GE, Goodman PJ, Haiman C, Hartge P, Hasan M, Helzlsouer KJ, Holly EA, Klein EA, Kogevinas M, Kurtz RJ, LeMarchand L, Malats N, Männistö S, Milne R, Neale RE, Ng K, Obazee O, Oberg AL, Orlow I, Patel AV, Peters U, Porta M, Rothman N, Scelo G, Sesso HD, Severi G, Sieri S, Silverman D, Sund M, Tjønneland A, Thornquist MD, Tobias GS, Trichopoulou A, Van Den Eeden SK, Visvanathan K, Wactawski-Wende J, Wentzensen N, White E, Yu H, Yuan C, Zeleniuch-Jacquotte A, Hoover R, Brown K, Kooperberg C, Risch HA, Jacobs EJ, Li D, Yu K, Shu XO, Chanock SJ, Wolpin BM, Stolzenberg-Solomon RZ, Chatterjee N, Klein AP, Smith JP, Kraft P, Shi J, Petersen GM, Zheng W, and Amundadottir LT

Subjects
Databases, Genetic, Gene Expression, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Transcriptome, Pancreatic Neoplasms genetics
Abstract

Background: Although 20 pancreatic cancer susceptibility loci have been identified through genome-wide association studies in individuals of European ancestry, much of its heritability remains unexplained and the genes responsible largely unknown., Methods: To discover novel pancreatic cancer risk loci and possible causal genes, we performed a pancreatic cancer transcriptome-wide association study in Europeans using three approaches: FUSION, MetaXcan, and Summary-MulTiXcan. We integrated genome-wide association studies summary statistics from 9040 pancreatic cancer cases and 12 496 controls, with gene expression prediction models built using transcriptome data from histologically normal pancreatic tissue samples (NCI Laboratory of Translational Genomics [n = 95] and Genotype-Tissue Expression v7 [n = 174] datasets) and data from 48 different tissues (Genotype-Tissue Expression v7, n = 74-421 samples)., Results: We identified 25 genes whose genetically predicted expression was statistically significantly associated with pancreatic cancer risk (false discovery rate < .05), including 14 candidate genes at 11 novel loci (1p36.12: CELA3B; 9q31.1: SMC2, SMC2-AS1; 10q23.31: RP11-80H5.9; 12q13.13: SMUG1; 14q32.33: BTBD6; 15q23: HEXA; 15q26.1: RCCD1; 17q12: PNMT, CDK12, PGAP3; 17q22: SUPT4H1; 18q11.22: RP11-888D10.3; and 19p13.11: PGPEP1) and 11 at six known risk loci (5p15.33: TERT, CLPTM1L, ZDHHC11B; 7p14.1: INHBA; 9q34.2: ABO; 13q12.2: PDX1; 13q22.1: KLF5; and 16q23.1: WDR59, CFDP1, BCAR1, TMEM170A). The association for 12 of these genes (CELA3B, SMC2, and PNMT at novel risk loci and TERT, CLPTM1L, INHBA, ABO, PDX1, KLF5, WDR59, CFDP1, and BCAR1 at known loci) remained statistically significant after Bonferroni correction., Conclusions: By integrating gene expression and genotype data, we identified novel pancreatic cancer risk loci and candidate functional genes that warrant further investigation., (Published by Oxford University Press 2020. This work is written by US Government employees and is in the public domain in the US.)

Published
2020
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