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

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

Research output: Contribution to journalArticle

129 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)994-1000
Number of pages7
JournalNature Genetics
Volume46
Issue number9
DOIs
Publication statusPublished - 2014

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Genome-Wide Association Study
Pancreatic Neoplasms
Odds Ratio
Confidence Intervals
Alleles
Genome
Exons

ASJC Scopus subject areas

  • Genetics

Cite this

Wolpin, B. M., Rizzato, C., Kraft, P., Kooperberg, C., Petersen, G. M., Wang, Z., ... Amundadottir, L. T. (2014). Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer. Nature Genetics, 46(9), 994-1000. https://doi.org/10.1038/ng.3052

Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer. / Wolpin, Brian M.; Rizzato, Cosmeri; Kraft, Peter; Kooperberg, Charles; Petersen, Gloria M.; Wang, Zhaoming; Arslan, Alan A.; Beane-Freeman, Laura; Bracci, Paige M.; Buring, Julie; Canzian, Federico; Duell, Eric J.; Gallinger, Steven; Giles, Graham G.; Goodman, Gary E.; Goodman, Phyllis J.; Jacobs, Eric J.; Kamineni, Aruna; Klein, Alison P.; Kolonel, Laurence N.; Kulke, Matthew H.; Li, Donghui; Malats, Núria; Olson, Sara H.; Risch, Harvey A.; Sesso, Howard D.; Visvanathan, Kala; White, Emily; Zheng, Wei; Abnet, Christian C.; Albanes, Demetrius; Andreotti, Gabriella; Austin, Melissa A.; Barfield, Richard; Basso, Daniela; Berndt, Sonja I.; Boutron-Ruault, Marie Christine; Brotzman, Michelle; Büchler, Markus W.; Bueno-De-Mesquita, H. Bas; Bugert, Peter; Burdette, Laurie; Campa, Daniele; Caporaso, Neil E.; Capurso, Gabriele; Chung, Charles; Cotterchio, Michelle; Costello, Eithne; Elena, Joanne; Funel, Niccola; Gaziano, J. Michael; Giese, Nathalia A.; Giovannucci, Edward L.; Goggins, Michael; Gorman, Megan J.; Gross, Myron; Haiman, Christopher A.; Hassan, Manal; Helzlsouer, Kathy J.; Henderson, Brian E.; Holly, Elizabeth A.; Hu, Nan; Hunter, David J.; Innocenti, Federico; Jenab, Mazda; Kaaks, Rudolf; Key, Timothy J.; Khaw, Kay Tee; Klein, Eric A.; Kogevinas, Manolis; Krogh, Vittorio; Kupcinskas, Juozas; Kurtz, Robert C.; Lacroix, Andrea; Landi, Maria T.; Landi, Stefano; Le Marchand, Loic; Mambrini, Andrea; Mannisto, Satu; Milne, Roger L.; Nakamura, Yusuke; Oberg, Ann L.; Owzar, Kouros; Patel, Alpa V.; Peeters, Petra H M; Peters, Ulrike; Pezzilli, Raffaele; Piepoli, Ada; Porta, Miquel; Real, Francisco X.; Riboli, Elio; Rothman, Nathaniel; Scarpa, Aldo; Shu, Xiao Ou; Silverman, Debra T.; Soucek, Pavel; Sund, Malin; Talar-Wojnarowska, Renata; Taylor, Philip R.; Theodoropoulos, George E.; Thornquist, Mark; Tjønneland, Anne; Tobias, Geoffrey S.; Trichopoulos, Dimitrios; Vodicka, Pavel; Wactawski-Wende, Jean; Wentzensen, Nicolas; Wu, Chen; Yu, Herbert; Yu, Kai; Zeleniuch-Jacquotte, Anne; Hoover, Robert; Hartge, Patricia; Fuchs, Charles; Chanock, Stephen J.; Stolzenberg-Solomon, Rachael S.; Amundadottir, Laufey T.

In: Nature Genetics, Vol. 46, No. 9, 2014, p. 994-1000.

Research output: Contribution to journalArticle

Wolpin, BM, Rizzato, C, Kraft, P, Kooperberg, C, Petersen, GM, Wang, Z, Arslan, AA, Beane-Freeman, L, Bracci, PM, Buring, J, Canzian, F, Duell, EJ, Gallinger, S, Giles, GG, Goodman, GE, Goodman, PJ, Jacobs, EJ, Kamineni, A, Klein, AP, Kolonel, LN, Kulke, MH, Li, D, Malats, N, Olson, SH, Risch, HA, Sesso, HD, Visvanathan, K, White, E, Zheng, W, Abnet, CC, Albanes, D, Andreotti, G, Austin, MA, Barfield, R, Basso, D, Berndt, SI, Boutron-Ruault, MC, Brotzman, M, Büchler, MW, Bueno-De-Mesquita, HB, Bugert, P, Burdette, L, Campa, D, Caporaso, NE, Capurso, G, Chung, C, Cotterchio, M, Costello, E, Elena, J, Funel, N, Gaziano, JM, Giese, NA, Giovannucci, EL, Goggins, M, Gorman, MJ, Gross, M, Haiman, CA, Hassan, M, Helzlsouer, KJ, Henderson, BE, Holly, EA, Hu, N, Hunter, DJ, Innocenti, F, Jenab, M, Kaaks, R, Key, TJ, Khaw, KT, Klein, EA, Kogevinas, M, Krogh, V, Kupcinskas, J, Kurtz, RC, Lacroix, A, Landi, MT, Landi, S, Le Marchand, L, Mambrini, A, Mannisto, S, Milne, RL, Nakamura, Y, Oberg, AL, Owzar, K, Patel, AV, Peeters, PHM, Peters, U, Pezzilli, R, Piepoli, A, Porta, M, Real, FX, Riboli, E, Rothman, N, Scarpa, A, Shu, XO, Silverman, DT, Soucek, P, Sund, M, Talar-Wojnarowska, R, Taylor, PR, Theodoropoulos, GE, Thornquist, M, Tjønneland, A, Tobias, GS, Trichopoulos, D, Vodicka, P, Wactawski-Wende, J, Wentzensen, N, Wu, C, Yu, H, Yu, K, Zeleniuch-Jacquotte, A, Hoover, R, Hartge, P, Fuchs, C, Chanock, SJ, Stolzenberg-Solomon, RS & Amundadottir, LT 2014, 'Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer', Nature Genetics, vol. 46, no. 9, pp. 994-1000. https://doi.org/10.1038/ng.3052
Wolpin BM, Rizzato C, Kraft P, Kooperberg C, Petersen GM, Wang Z et al. Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer. Nature Genetics. 2014;46(9):994-1000. https://doi.org/10.1038/ng.3052
Wolpin, Brian M. ; Rizzato, Cosmeri ; Kraft, Peter ; Kooperberg, Charles ; Petersen, Gloria M. ; Wang, Zhaoming ; Arslan, Alan A. ; Beane-Freeman, Laura ; Bracci, Paige M. ; Buring, Julie ; Canzian, Federico ; Duell, Eric J. ; Gallinger, Steven ; Giles, Graham G. ; Goodman, Gary E. ; Goodman, Phyllis J. ; Jacobs, Eric J. ; Kamineni, Aruna ; Klein, Alison P. ; Kolonel, Laurence N. ; Kulke, Matthew H. ; Li, Donghui ; Malats, Núria ; Olson, Sara H. ; Risch, Harvey A. ; Sesso, Howard D. ; Visvanathan, Kala ; White, Emily ; Zheng, Wei ; Abnet, Christian C. ; Albanes, Demetrius ; Andreotti, Gabriella ; Austin, Melissa A. ; Barfield, Richard ; Basso, Daniela ; Berndt, Sonja I. ; Boutron-Ruault, Marie Christine ; Brotzman, Michelle ; Büchler, Markus W. ; Bueno-De-Mesquita, H. Bas ; Bugert, Peter ; Burdette, Laurie ; Campa, Daniele ; Caporaso, Neil E. ; Capurso, Gabriele ; Chung, Charles ; Cotterchio, Michelle ; Costello, Eithne ; Elena, Joanne ; Funel, Niccola ; Gaziano, J. Michael ; Giese, Nathalia A. ; Giovannucci, Edward L. ; Goggins, Michael ; Gorman, Megan J. ; Gross, Myron ; Haiman, Christopher A. ; Hassan, Manal ; Helzlsouer, Kathy J. ; Henderson, Brian E. ; Holly, Elizabeth A. ; Hu, Nan ; Hunter, David J. ; Innocenti, Federico ; Jenab, Mazda ; Kaaks, Rudolf ; Key, Timothy J. ; Khaw, Kay Tee ; Klein, Eric A. ; Kogevinas, Manolis ; Krogh, Vittorio ; Kupcinskas, Juozas ; Kurtz, Robert C. ; Lacroix, Andrea ; Landi, Maria T. ; Landi, Stefano ; Le Marchand, Loic ; Mambrini, Andrea ; Mannisto, Satu ; Milne, Roger L. ; Nakamura, Yusuke ; Oberg, Ann L. ; Owzar, Kouros ; Patel, Alpa V. ; Peeters, Petra H M ; Peters, Ulrike ; Pezzilli, Raffaele ; Piepoli, Ada ; Porta, Miquel ; Real, Francisco X. ; Riboli, Elio ; Rothman, Nathaniel ; Scarpa, Aldo ; Shu, Xiao Ou ; Silverman, Debra T. ; Soucek, Pavel ; Sund, Malin ; Talar-Wojnarowska, Renata ; Taylor, Philip R. ; Theodoropoulos, George E. ; Thornquist, Mark ; Tjønneland, Anne ; Tobias, Geoffrey S. ; Trichopoulos, Dimitrios ; Vodicka, Pavel ; Wactawski-Wende, Jean ; Wentzensen, Nicolas ; Wu, Chen ; Yu, Herbert ; Yu, Kai ; Zeleniuch-Jacquotte, Anne ; Hoover, Robert ; Hartge, Patricia ; Fuchs, Charles ; Chanock, Stephen J. ; Stolzenberg-Solomon, Rachael S. ; Amundadottir, Laufey T. / Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer. In: Nature Genetics. 2014 ; Vol. 46, No. 9. pp. 994-1000.
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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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T1 - Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer

AU - Wolpin, Brian M.

AU - Rizzato, Cosmeri

AU - Kraft, Peter

AU - Kooperberg, Charles

AU - Petersen, Gloria M.

AU - Wang, Zhaoming

AU - Arslan, Alan A.

AU - Beane-Freeman, Laura

AU - Bracci, Paige M.

AU - Buring, Julie

AU - Canzian, Federico

AU - Duell, Eric J.

AU - Gallinger, Steven

AU - Giles, Graham G.

AU - Goodman, Gary E.

AU - Goodman, Phyllis J.

AU - Jacobs, Eric J.

AU - Kamineni, Aruna

AU - Klein, Alison P.

AU - Kolonel, Laurence N.

AU - Kulke, Matthew H.

AU - Li, Donghui

AU - Malats, Núria

AU - Olson, Sara H.

AU - Risch, Harvey A.

AU - Sesso, Howard D.

AU - Visvanathan, Kala

AU - White, Emily

AU - Zheng, Wei

AU - Abnet, Christian C.

AU - Albanes, Demetrius

AU - Andreotti, Gabriella

AU - Austin, Melissa A.

AU - Barfield, Richard

AU - Basso, Daniela

AU - Berndt, Sonja I.

AU - Boutron-Ruault, Marie Christine

AU - Brotzman, Michelle

AU - Büchler, Markus W.

AU - Bueno-De-Mesquita, H. Bas

AU - Bugert, Peter

AU - Burdette, Laurie

AU - Campa, Daniele

AU - Caporaso, Neil E.

AU - Capurso, Gabriele

AU - Chung, Charles

AU - Cotterchio, Michelle

AU - Costello, Eithne

AU - Elena, Joanne

AU - Funel, Niccola

AU - Gaziano, J. Michael

AU - Giese, Nathalia A.

AU - Giovannucci, Edward L.

AU - Goggins, Michael

AU - Gorman, Megan J.

AU - Gross, Myron

AU - Haiman, Christopher A.

AU - Hassan, Manal

AU - Helzlsouer, Kathy J.

AU - Henderson, Brian E.

AU - Holly, Elizabeth A.

AU - Hu, Nan

AU - Hunter, David J.

AU - Innocenti, Federico

AU - Jenab, Mazda

AU - Kaaks, Rudolf

AU - Key, Timothy J.

AU - Khaw, Kay Tee

AU - Klein, Eric A.

AU - Kogevinas, Manolis

AU - Krogh, Vittorio

AU - Kupcinskas, Juozas

AU - Kurtz, Robert C.

AU - Lacroix, Andrea

AU - Landi, Maria T.

AU - Landi, Stefano

AU - Le Marchand, Loic

AU - Mambrini, Andrea

AU - Mannisto, Satu

AU - Milne, Roger L.

AU - Nakamura, Yusuke

AU - Oberg, Ann L.

AU - Owzar, Kouros

AU - Patel, Alpa V.

AU - Peeters, Petra H M

AU - Peters, Ulrike

AU - Pezzilli, Raffaele

AU - Piepoli, Ada

AU - Porta, Miquel

AU - Real, Francisco X.

AU - Riboli, Elio

AU - Rothman, Nathaniel

AU - Scarpa, Aldo

AU - Shu, Xiao Ou

AU - Silverman, Debra T.

AU - Soucek, Pavel

AU - Sund, Malin

AU - Talar-Wojnarowska, Renata

AU - Taylor, Philip R.

AU - Theodoropoulos, George E.

AU - Thornquist, Mark

AU - Tjønneland, Anne

AU - Tobias, Geoffrey S.

AU - Trichopoulos, Dimitrios

AU - Vodicka, Pavel

AU - Wactawski-Wende, Jean

AU - Wentzensen, Nicolas

AU - Wu, Chen

AU - Yu, Herbert

AU - Yu, Kai

AU - Zeleniuch-Jacquotte, Anne

AU - Hoover, Robert

AU - Hartge, Patricia

AU - Fuchs, Charles

AU - Chanock, Stephen J.

AU - Stolzenberg-Solomon, Rachael S.

AU - Amundadottir, Laufey T.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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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