Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer

Wolpin, Brian M.; Bm, Wolpin; Rizzato, Cosmeri; Kraft, Peter; Kooperberg, Charles; Petersen, Gloria M.; Gm, Petersen; Wang, Zhaoming; Arslan, Alan A.; Beane-Freeman, Laura; Pm, Bracci; Bracci, Paige M.; Buring, Julie; Ej, Duell; Canzian, Federico; Duell, Eric J.; Gallinger, Steven; Gg, Giles; Giles, Graham G.; Goodman, Gary E.; Ge, Goodman; Goodman, Phyllis J.; Pj, Goodman; Jacobs, Eric J.; Ej, Jacobs; Kamineni, Aruna; Klein, Alison P.; Ap, Klein; Kolonel, Laurence N.; Ln, Kolonel; Kulke, Matthew H.; Mh, Kulke; Li, Donghui; Malats, Núria; Olson, Sara H.; Sh, Olson; Risch, Harvey A.; Ha, Risch; Sesso, Howard D.; Visvanathan, Kala; Hd, Sesso; White, Emily; Zheng, Wei; Cc, Abnet; Abnet, Christian C.; Albanes, Demetrius; Andreotti, Gabriella; Austin, Melissa A.; Ma, Austin; Barfield, Richard; Basso, Daniela; Berndt, Sonja I.; Si, Berndt; Boutron-Ruault, Marie-Christine; Mc, Boutron Ruault; Brotzman, Michelle; Büchler, Markus W.; Buechler, Markus W.; Mw, B?chler; Bueno-De-Mesquita, H. Bas; Bugert, Peter; Bas Bueno de Mesquita, H.; Burdette, Laurie; Campa, Daniele; Hb, Bueno de Mesquita; Caporaso, Neil E.; Capurso, Gabriele; Ne, Caporaso; Chung, Charles; Cotterchio, Michelle; Costello, Eithne; Elena, Joanne; Funel, Niccola; Jm, Gaziano; Michael Gaziano, J.; Gaziano, J. Michael; Giese, Nathalia A.; Na, Giese; Giovannucci, Edward L.; Goggins, Michael; El, Giovannucci; Gorman, Megan J.; Gross, Myron; Mj, Gorman; Haiman, Christopher A.; Hassan, Manal; Ca, Haiman; Helzlsouer, Kathy J.; Henderson, Brian E.; Kj, Helzlsouer; Holly, Elizabeth A.; Hu, Nan; Be, Henderson; Hunter, David J.; Innocenti, Federico; Ea, Holly; Jenab, Mazda; Kaaks, Rudolf; Key, Timothy J.; Dj, Hunter; Khaw, Kay-Tee; Klein, Eric A.; Tj, Key; Kogevinas, Manolis; Krogh, Vittorio; Kt, Khaw; Kupcinskas, Juozas; Kurtz, Robert C.; Ea, Klein; LaCroix, Andrea; Landi, Maria T.; Rc, Kurtz; Landi, Stefano; Le Marchand, Loic; Mambrini, Andrea; Mt, Landi; Mannisto, Satu; Milne, Roger L.; Marchand, Loic Le; Nakamura, Yusuke; Oberg, Ann L.; Rl, Milne; Owzar, Kouros; Patel, Alpa V.; Al, Oberg; Peeters, Petra H. M.; Peters, Ulrike; Av, Patel; Pezzilli, Raffaele; Piepoli, Ada; Ph, Peeters; Porta, Miquel; Real, Francisco X.; Fx, Real; Riboli, Elio; Rothman, Nathaniel; Scarpa, Aldo; Shu, Xiao-Ou; Xo, Shu; Silverman, Debra T.; Dt, Silverman; Soucek, Pavel; Sund, Malin; Talar-Wojnarowska, Renata; Taylor, Philip R.; Pr, Taylor; Theodoropoulos, George E.; Ge, Theodoropoulos; Thornquist, Mark; Tjønneland, Anne; Tj?nneland, A.; Tobias, Geoffrey S.; Trichopoulos, Dimitrios; Gs, Tobias; Vodicka, Pavel; Wactawski-Wende, Jean; Wentzensen, Nicolas; Wu, Chen; Yu, Herbert; Yu, Kai; Zeleniuch-Jacquotte, Anne; Hoover, Robert; Sj, Chanock; Hartge, Patricia; Fuchs, Charles; Rs, Stolzenberg Solomon; Chanock, Stephen J.; Stolzenberg-Solomon, Rachael S.; Lt, Amundadottir; Amundadottir, Laufey T.; Aa, Arslan

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Alan Arslan
Wolpin et al., 2014

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Nature Research, Nature Genetics, 9(46), p. 994-1000, 2014

DOI: 10.1038/ng.3052

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@article{Wolpin2014,
  abstract = {We performed a multistage genome-wide association study including 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Four new loci reached genome-wide significance: rs6971499 at 7q32.3 (LINC-PINT, per-allele odds ratio (OR) = 0.79, 95% confidence interval (CI) 0.74-0.84, P = 3.0 × 10(-12)), rs7190458 at 16q23.1 (BCAR1/CTRB1/CTRB2, OR = 1.46, 95% CI 1.30-1.65, P = 1.1 × 10(-10)), rs9581943 at 13q12.2 (PDX1, OR = 1.15, 95% CI 1.10-1.20, P = 2.4 × 10(-9)) and rs16986825 at 22q12.1 (ZNRF3, OR = 1.18, 95% CI 1.12-1.25, P = 1.2 × 10(-8)). We identified an independent signal in exon 2 of TERT at the established region 5p15.33 (rs2736098, OR = 0.80, 95% CI 0.76-0.85, P = 9.8 × 10(-14)). We also identified a locus at 8q24.21 (rs1561927, P = 1.3 × 10(-7)) that approached genome-wide significance located 455 kb telomeric of PVT1. Our study identified multiple new susceptibility alleles for pancreatic cancer that are worthy of follow-up studies.},
  author = {Wolpin, Brian M. and Bm, Wolpin and Rizzato, Cosmeri and Kraft, Peter and Kooperberg, Charles and Petersen, Gloria M. and Gm, Petersen and Wang, Zhaoming and Arslan, Alan A. and Beane-Freeman, Laura and Pm, Bracci and Bracci, Paige M. and Buring, Julie and Ej, Duell and Canzian, Federico and Duell, Eric J. and Gallinger, Steven and Gg, Giles and Giles, Graham G. and Goodman, Gary E. and Ge, Goodman and Goodman, Phyllis J. and Pj, Goodman and Jacobs, Eric J. and Ej, Jacobs and Kamineni, Aruna and Klein, Alison P. and Ap, Klein and Kolonel, Laurence N. and Ln, Kolonel and Kulke, Matthew H. and Mh, Kulke and Li, Donghui and Malats, Núria and Olson, Sara H. and Sh, Olson and Risch, Harvey A. and Ha, Risch and Sesso, Howard D. and Visvanathan, Kala and Hd, Sesso and White, Emily and Zheng, Wei and Cc, Abnet and Abnet, Christian C. and Albanes, Demetrius and Andreotti, Gabriella and Austin, Melissa A. and Ma, Austin and Barfield, Richard and Basso, Daniela and Berndt, Sonja I. and Si, Berndt and Boutron-Ruault, Marie-Christine and Mc, Boutron Ruault and Brotzman, Michelle and Büchler, Markus W. and Buechler, Markus W. and Mw, B?chler and Bueno-De-Mesquita, H. Bas and Bugert, Peter and Bas Bueno de Mesquita, H. and Burdette, Laurie and Campa, Daniele and Hb, Bueno de Mesquita and Caporaso, Neil E. and Capurso, Gabriele and Ne, Caporaso and Chung, Charles and Cotterchio, Michelle and Costello, Eithne and Elena, Joanne and Funel, Niccola and Jm, Gaziano and Michael Gaziano, J. and Gaziano, J. Michael and Giese, Nathalia A. and Na, Giese and Giovannucci, Edward L. and Goggins, Michael and El, Giovannucci and Gorman, Megan J. and Gross, Myron and Mj, Gorman and Haiman, Christopher A. and Hassan, Manal and Ca, Haiman and Helzlsouer, Kathy J. and Henderson, Brian E. and Kj, Helzlsouer and Holly, Elizabeth A. and Hu, Nan and Be, Henderson and Hunter, David J. and Innocenti, Federico and Ea, Holly and Jenab, Mazda and Kaaks, Rudolf and Key, Timothy J. and Dj, Hunter and Khaw, Kay-Tee and Klein, Eric A. and Tj, Key and Kogevinas, Manolis and Krogh, Vittorio and Kt, Khaw and Kupcinskas, Juozas and Kurtz, Robert C. and Ea, Klein and LaCroix, Andrea and Landi, Maria T. and Rc, Kurtz and Landi, Stefano and Le Marchand, Loic and Mambrini, Andrea and Mt, Landi and Mannisto, Satu and Milne, Roger L. and Marchand, Loic Le and Nakamura, Yusuke and Oberg, Ann L. and Rl, Milne and Owzar, Kouros and Patel, Alpa V. and Al, Oberg and Peeters, Petra H. M. and Peters, Ulrike and Av, Patel and Pezzilli, Raffaele and Piepoli, Ada and Ph, Peeters and Porta, Miquel and Real, Francisco X. and Fx, Real and Riboli, Elio and Rothman, Nathaniel and Scarpa, Aldo and Shu, Xiao-Ou and Xo, Shu and Silverman, Debra T. and Dt, Silverman and Soucek, Pavel and Sund, Malin and Talar-Wojnarowska, Renata and Taylor, Philip R. and Pr, Taylor and Theodoropoulos, George E. and Ge, Theodoropoulos and Thornquist, Mark and Tjønneland, Anne and Tj?nneland, A. and Tobias, Geoffrey S. and Trichopoulos, Dimitrios and Gs, Tobias and Vodicka, Pavel and Wactawski-Wende, Jean and Wentzensen, Nicolas and Wu, Chen and Yu, Herbert and Yu, Kai and Zeleniuch-Jacquotte, Anne and Hoover, Robert and Sj, Chanock and Hartge, Patricia and Fuchs, Charles and Rs, Stolzenberg Solomon and Chanock, Stephen J. and Stolzenberg-Solomon, Rachael S. and Lt, Amundadottir and Amundadottir, Laufey T. and Aa, Arslan},
  doi = {10.1038/ng.3052},
  journal = {Nature Genetics},
  month = {aug},
  pages = {994-1000},
  title = {Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer},
  url = {http://www.nature.com/articles/ng.3052.pdf},
  volume = {46},
  year = {2014}
}

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Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer

Journal article published in 2014 by Brian M. Wolpin, Wolpin Bm, Cosmeri Rizzato, Peter Kraft, Charles Kooperberg, Gloria M. Petersen, Petersen Gm, Zhaoming Wang, Alan A. Arslan

, Laura Beane-Freeman, Bracci Pm, Paige M. Bracci, Julie Buring, Duell Ej, Federico Canzian and other authors. Brian M. Wolpin, Wolpin Bm, Cosmeri Rizzato, Peter Kraft, Charles Kooperberg, Gloria M. Petersen, Petersen Gm, Zhaoming Wang, Alan A. Arslan

, Laura Beane-Freeman, Bracci Pm, Paige M. Bracci, Julie Buring, Duell Ej, Federico Canzian, Eric J. Duell

, Steven Gallinger, Giles Gg, Graham G. Giles

, Gary E. Goodman, Goodman Ge, Phyllis J. Goodman, Goodman Pj, Eric J. Jacobs, Jacobs Ej, Aruna Kamineni, Alison P. Klein, Klein Ap, Laurence N. Kolonel, Kolonel Ln, Matthew H. Kulke, Kulke Mh, Donghui Li, Núria Malats, Sara H. Olson, Olson Sh, Harvey A. Risch, Risch Ha, Howard D. Sesso, Kala Visvanathan, Sesso Hd, Emily White, Wei Zheng, Abnet Cc, Christian C. Abnet

, Demetrius Albanes, Gabriella Andreotti, Melissa A. Austin, Austin Ma, Richard Barfield, Daniela Basso, Sonja I. Berndt, Berndt Si, Marie-Christine Boutron-Ruault, Boutron Ruault Mc, Michelle Brotzman, Markus W. Büchler, Markus W. Buechler, B?chler Mw, H. Bas Bueno-De-Mesquita, Peter Bugert, H. Bas Bueno de Mesquita, Laurie Burdette, Daniele Campa, Bueno de Mesquita Hb, Neil E. Caporaso, Gabriele Capurso

, Caporaso Ne, Charles Chung, Michelle Cotterchio, Eithne Costello, Joanne Elena, Niccola Funel

, Gaziano Jm, J. Michael Gaziano, J. Michael Gaziano, Nathalia A. Giese, Giese Na, Edward L. Giovannucci, Michael Goggins, Giovannucci El, Megan J. Gorman, Myron Gross, Gorman Mj, Christopher A. Haiman, Manal Hassan, Haiman Ca, Kathy J. Helzlsouer, Brian E. Henderson, Helzlsouer Kj, Elizabeth A. Holly, Nan Hu, Henderson Be, David J. Hunter, Federico Innocenti, Holly Ea, Mazda Jenab

, Rudolf Kaaks, Timothy J. Key, Hunter Dj, Kay-Tee Khaw, Eric A. Klein, Key Tj, Manolis Kogevinas, Vittorio Krogh, Khaw Kt, Juozas Kupcinskas

, Robert C. Kurtz, Klein Ea, Andrea LaCroix, Maria T. Landi, Kurtz Rc, Stefano Landi, Loic Le Marchand, Andrea Mambrini, Landi Mt, Satu Mannisto, Roger L. Milne, Loic Le Marchand, Yusuke Nakamura, Ann L. Oberg, Milne Rl, Kouros Owzar, Alpa V. Patel, Oberg Al, Petra H. M. Peeters, Ulrike Peters, Patel Av, Raffaele Pezzilli, Ada Piepoli, Peeters Ph, Miquel Porta

, Francisco X. Real

, Real Fx, Elio Riboli, Nathaniel Rothman, Aldo Scarpa

, Xiao-Ou Shu, Shu Xo, Debra T. Silverman, Silverman Dt, Pavel Soucek

, Malin Sund, Renata Talar-Wojnarowska, Philip R. Taylor, Taylor Pr, George E. Theodoropoulos, Theodoropoulos Ge, Mark Thornquist, Anne Tjønneland, A. Tj?nneland, Geoffrey S. Tobias, Dimitrios Trichopoulos, Tobias Gs, Pavel Vodicka, Jean Wactawski-Wende, Nicolas Wentzensen, Chen Wu

, Herbert Yu

, Kai Yu, Anne Zeleniuch-Jacquotte

, Robert Hoover, Chanock Sj, Patricia Hartge, Charles Fuchs, Stolzenberg Solomon Rs, Stephen J. Chanock, Rachael S. Stolzenberg-Solomon, Amundadottir Lt, Laufey T. Amundadottir

, Arslan Aa

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Abstract

We performed a multistage genome-wide association study including 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Four new loci reached genome-wide significance: rs6971499 at 7q32.3 (LINC-PINT, per-allele odds ratio (OR) = 0.79, 95% confidence interval (CI) 0.74-0.84, P = 3.0 × 10(-12)), rs7190458 at 16q23.1 (BCAR1/CTRB1/CTRB2, OR = 1.46, 95% CI 1.30-1.65, P = 1.1 × 10(-10)), rs9581943 at 13q12.2 (PDX1, OR = 1.15, 95% CI 1.10-1.20, P = 2.4 × 10(-9)) and rs16986825 at 22q12.1 (ZNRF3, OR = 1.18, 95% CI 1.12-1.25, P = 1.2 × 10(-8)). We identified an independent signal in exon 2 of TERT at the established region 5p15.33 (rs2736098, OR = 0.80, 95% CI 0.76-0.85, P = 9.8 × 10(-14)). We also identified a locus at 8q24.21 (rs1561927, P = 1.3 × 10(-7)) that approached genome-wide significance located 455 kb telomeric of PVT1. Our study identified multiple new susceptibility alleles for pancreatic cancer that are worthy of follow-up studies.

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Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer

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