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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number556
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

Fingerprint

genome
loci
Pancreatic Neoplasms
Meta-Analysis
Genes
cancer
Genome
magnetic permeability
Pancreatic Diseases
Quantitative Trait Loci
Neoplasm Genes
Genome-Wide Association Study
death
genes
Alleles
Research

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Klein, A., Wolpin, B. M., Risch, H. A., Stolzenberg-Solomon, R. Z., Mocci, E., Zhang, M., ... Amundadottir, L. T. (2018). Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer. Nature Communications, 9(1), [556]. https://doi.org/10.1038/s41467-018-02942-5

Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer. / Klein, Alison; 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 S; 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.

In: Nature Communications, Vol. 9, No. 1, 556, 01.12.2018.

Research output: Contribution to journalArticle

Klein, A, Wolpin, BM, Risch, HA, Stolzenberg-Solomon, RZ, Mocci, E, Zhang, M, Canzian, F, Childs, EJ, Hoskins, JW, Jermusyk, A, Zhong, J, Chen, F, Albanes, D, Andreotti, G, Arslan, AA, Babic, A, Bamlet, WR, Beane-Freeman, L, Berndt, SI, Blackford, A, Borges, M, Borgida, A, Bracci, PM, Brais, L, Brennan, P, Brenner, H, Bueno-De-Mesquita, B, Buring, J, Campa, D, Capurso, G, Cavestro, GM, Chaffee, KG, Chung, CC, Cleary, S, Cotterchio, M, Dijk, F, Duell, EJ, Foretova, L, Fuchs, C, Funel, N, Gallinger, S, Gaziano, JMM, Gazouli, M, Giles, GG, Giovannucci, E, Goggins, MS, Goodman, GE, Goodman, PJ, Hackert, T, Haiman, C, Hartge, P, Hasan, M, Hegyi, P, Helzlsouer, KJ, Herman, J, Holcatova, I, Holly, EA, Hoover, R, Hung, RJ, Jacobs, EJ, Jamroziak, K, Janout, V, Kaaks, R, Khaw, KT, Klein, EA, Kogevinas, M, Kooperberg, C, Kulke, MH, Kupcinskas, J, Kurtz, RJ, Laheru, D, Landi, S, Lawlor, RT, Lee, IM, Lemarchand, L, Lu, L, Malats, N, Mambrini, A, Mannisto, S, Milne, RL, Mohelníková-Duchoňová, B, Neale, RE, Neoptolemos, JP, Oberg, AL, Olson, SH, Orlow, I, Pasquali, C, Patel, AV, Peters, U, Pezzilli, R, Porta, M, Real, FX, Rothman, N, Scelo, G, Sesso, HD, Severi, G, Shu, XO, Silverman, D, Smith, JP, Soucek, P, Sund, M, Talar-Wojnarowska, R, Tavano, F, Thornquist, MD, Tobias, GS, Van Den Eeden, SK, Vashist, Y, Visvanathan, K, Vodicka, P, Wactawski-Wende, J, Wang, Z, Wentzensen, N, White, E, Yu, H, Yu, K, Zeleniuch-Jacquotte, A, Zheng, W, Kraft, P, Li, D, Chanock, S, Obazee, O, Petersen, GM & Amundadottir, LT 2018, 'Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer', Nature Communications, vol. 9, no. 1, 556. https://doi.org/10.1038/s41467-018-02942-5
Klein, Alison ; 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 S ; 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. / Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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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.",
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AU - Risch, Harvey A.

AU - Stolzenberg-Solomon, Rachael Z.

AU - Mocci, Evelina

AU - Zhang, Mingfeng

AU - Canzian, Federico

AU - Childs, Erica J.

AU - Hoskins, Jason W.

AU - Jermusyk, Ashley

AU - Zhong, Jun

AU - Chen, Fei

AU - Albanes, Demetrius

AU - Andreotti, Gabriella

AU - Arslan, Alan A.

AU - Babic, Ana

AU - Bamlet, William R.

AU - Beane-Freeman, Laura

AU - Berndt, Sonja I.

AU - Blackford, Amanda

AU - Borges, Michael

AU - Borgida, Ayelet

AU - Bracci, Paige M.

AU - Brais, Lauren

AU - Brennan, Paul

AU - Brenner, Hermann

AU - Bueno-De-Mesquita, Bas

AU - Buring, Julie

AU - Campa, Daniele

AU - Capurso, Gabriele

AU - Cavestro, Giulia Martina

AU - Chaffee, Kari G.

AU - Chung, Charles C.

AU - Cleary, Sean

AU - Cotterchio, Michelle

AU - Dijk, Frederike

AU - Duell, Eric J.

AU - Foretova, Lenka

AU - Fuchs, Charles

AU - Funel, Niccola

AU - Gallinger, Steven

AU - Gaziano, J. Michael M.

AU - Gazouli, Maria

AU - Giles, Graham G.

AU - Giovannucci, Edward

AU - Goggins, Michael S

AU - Goodman, Gary E.

AU - Goodman, Phyllis J.

AU - Hackert, Thilo

AU - Haiman, Christopher

AU - Hartge, Patricia

AU - Hasan, Manal

AU - Hegyi, Peter

AU - Helzlsouer, Kathy J.

AU - Herman, Joseph

AU - Holcatova, Ivana

AU - Holly, Elizabeth A.

AU - Hoover, Robert

AU - Hung, Rayjean J.

AU - Jacobs, Eric J.

AU - Jamroziak, Krzysztof

AU - Janout, Vladimir

AU - Kaaks, Rudolf

AU - Khaw, Kay Tee

AU - Klein, Eric A.

AU - Kogevinas, Manolis

AU - Kooperberg, Charles

AU - Kulke, Matthew H.

AU - Kupcinskas, Juozas

AU - Kurtz, Robert J.

AU - Laheru, Daniel

AU - Landi, Stefano

AU - Lawlor, Rita T.

AU - Lee, I. Min

AU - Lemarchand, Loic

AU - Lu, Lingeng

AU - Malats, Núria

AU - Mambrini, Andrea

AU - Mannisto, Satu

AU - Milne, Roger L.

AU - Mohelníková-Duchoňová, Beatrice

AU - Neale, Rachel E.

AU - Neoptolemos, John P.

AU - Oberg, Ann L.

AU - Olson, Sara H.

AU - Orlow, Irene

AU - Pasquali, Claudio

AU - Patel, Alpa V.

AU - Peters, Ulrike

AU - Pezzilli, Raffaele

AU - Porta, Miquel

AU - Real, Francisco X.

AU - Rothman, Nathaniel

AU - Scelo, Ghislaine

AU - Sesso, Howard D.

AU - Severi, Gianluca

AU - Shu, Xiao Ou

AU - Silverman, Debra

AU - Smith, Jill P.

AU - Soucek, Pavel

AU - Sund, Malin

AU - Talar-Wojnarowska, Renata

AU - Tavano, Francesca

AU - Thornquist, Mark D.

AU - Tobias, Geoffrey S.

AU - Van Den Eeden, Stephen K.

AU - Vashist, Yogesh

AU - Visvanathan, Kala

AU - Vodicka, Pavel

AU - Wactawski-Wende, Jean

AU - Wang, Zhaoming

AU - Wentzensen, Nicolas

AU - White, Emily

AU - Yu, Herbert

AU - Yu, Kai

AU - Zeleniuch-Jacquotte, Anne

AU - Zheng, Wei

AU - Kraft, Peter

AU - Li, Donghui

AU - Chanock, Stephen

AU - Obazee, Ofure

AU - Petersen, Gloria M.

AU - Amundadottir, Laufey T.

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N2 - 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.

AB - 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.

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