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. Kolonel; Matthew 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

doi:10.1038/ng.3052

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

Quantitative Health Sciences

Research output: Contribution to journal › Article › peer-review

178 Scopus citations

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 language	English (US)
Pages (from-to)	994-1000
Number of pages	7
Journal	Nature Genetics
Volume	46
Issue number	9
DOIs	https://doi.org/10.1038/ng.3052
State	Published - 2014

ASJC Scopus subject areas

Genetics

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10.1038/ng.3052

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Wolpin, B. M., Rizzato, C., Kraft, P., Kooperberg, C., Petersen, G. M., Wang, Z., Arslan, A. A., Beane-Freeman, L., Bracci, P. M., Buring, J., Canzian, F., Duell, E. J., Gallinger, S., Giles, G. G., Goodman, G. E., Goodman, P. J., Jacobs, E. J., Kamineni, A., Klein, A. P., ... 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

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

@article{1839c61b78f64d63a818dfc71a497932,

title = "Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer",

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 Cosmeri Rizzato and Peter Kraft and Charles Kooperberg and Petersen, {Gloria M.} and Zhaoming Wang and Arslan, {Alan A.} and Laura Beane-Freeman and Bracci, {Paige M.} and Julie Buring and Federico Canzian and Duell, {Eric J.} and Steven Gallinger and Giles, {Graham G.} and Goodman, {Gary E.} and Goodman, {Phyllis J.} and Jacobs, {Eric J.} and Aruna Kamineni and Klein, {Alison P.} and Kolonel, {Laurence N.} and Kulke, {Matthew H.} and Donghui Li and N{\'u}ria Malats and Olson, {Sara H.} and Risch, {Harvey A.} and Sesso, {Howard D.} and Kala Visvanathan and Emily White and Wei Zheng and Abnet, {Christian C.} and Demetrius Albanes and Gabriella Andreotti and Austin, {Melissa A.} and Richard Barfield and Daniela Basso and Berndt, {Sonja I.} and Boutron-Ruault, {Marie Christine} and Michelle Brotzman and B{\"u}chler, {Markus W.} and Bueno-De-Mesquita, {H. Bas} and Peter Bugert and Laurie Burdette and Daniele Campa and Caporaso, {Neil E.} and Gabriele Capurso and Charles Chung and Michelle Cotterchio and Eithne Costello and Joanne Elena and Niccola Funel and Gaziano, {J. Michael} and Giese, {Nathalia A.} and Giovannucci, {Edward L.} and Michael Goggins and Gorman, {Megan J.} and Myron Gross and Haiman, {Christopher A.} and Manal Hassan and Helzlsouer, {Kathy J.} and Henderson, {Brian E.} and Holly, {Elizabeth A.} and Nan Hu and Hunter, {David J.} and Federico Innocenti and Mazda Jenab and Rudolf Kaaks and Key, {Timothy J.} and Khaw, {Kay Tee} and Klein, {Eric A.} and Manolis Kogevinas and Vittorio Krogh and Juozas Kupcinskas and Kurtz, {Robert C.} and Andrea Lacroix and Landi, {Maria T.} and Stefano Landi and {Le Marchand}, Loic and Andrea Mambrini and Satu Mannisto and Milne, {Roger L.} and Yusuke Nakamura and Oberg, {Ann L.} and Kouros Owzar and Patel, {Alpa V.} and Peeters, {Petra H.M.} and Ulrike Peters and Raffaele Pezzilli and Ada Piepoli and Miquel Porta and Real, {Francisco X.} and Elio Riboli and Nathaniel Rothman and Aldo Scarpa and Shu, {Xiao Ou} and Silverman, {Debra T.} and Pavel Soucek and Malin Sund and Renata Talar-Wojnarowska and Taylor, {Philip R.} and Theodoropoulos, {George E.} and Mark Thornquist and Anne Tj{\o}nneland and Tobias, {Geoffrey S.} and Dimitrios Trichopoulos and Pavel Vodicka and Jean Wactawski-Wende and Nicolas Wentzensen and Chen Wu and Herbert Yu and Kai Yu and Anne Zeleniuch-Jacquotte and Robert Hoover and Patricia Hartge and Charles Fuchs and Chanock, {Stephen J.} and Stolzenberg-Solomon, {Rachael S.} and Amundadottir, {Laufey T.}",

note = "Funding Information: This project was funded in whole or in part with federal funds from the National Cancer Institute (NCI), US National Institutes of Health (NIH) under contract number HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the US Department of Health and Human Services, and mention of trade names, commercial products or organizations does not imply endorsement by the US government. Major support for PanScan III sample identification and processing was provided by the Lustgarten Foundation for Pancreatic Cancer Research. Additional support was received from NIH/NCI K07 CA140790, the American Society of Clinical Oncology Conquer Cancer Foundation, the Howard Hughes Medical Institute, the Lustgarten Foundation, the Robert T. and Judith B. Hale Fund for Pancreatic Cancer Research and Promises for Purple to B.M.W. A full list of acknowledgments for each participating study is provided in the Supplementary Note. Publisher Copyright: {\textcopyright} 2014 Nature America, Inc. All rights reserved.",

year = "2014",

doi = "10.1038/ng.3052",

language = "English (US)",

volume = "46",

pages = "994--1000",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "9",

}

TY - JOUR

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.

N1 - Funding Information: This project was funded in whole or in part with federal funds from the National Cancer Institute (NCI), US National Institutes of Health (NIH) under contract number HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the US Department of Health and Human Services, and mention of trade names, commercial products or organizations does not imply endorsement by the US government. Major support for PanScan III sample identification and processing was provided by the Lustgarten Foundation for Pancreatic Cancer Research. Additional support was received from NIH/NCI K07 CA140790, the American Society of Clinical Oncology Conquer Cancer Foundation, the Howard Hughes Medical Institute, the Lustgarten Foundation, the Robert T. and Judith B. Hale Fund for Pancreatic Cancer Research and Promises for Purple to B.M.W. A full list of acknowledgments for each participating study is provided in the Supplementary Note. Publisher Copyright: © 2014 Nature America, Inc. All rights reserved.

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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U2 - 10.1038/ng.3052

DO - 10.1038/ng.3052

M3 - Article

C2 - 25086665

AN - SCOPUS:84938423709

VL - 46

SP - 994

EP - 1000

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 9

ER -

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

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