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

Alison P. 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 Blackford; Michael 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 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

doi:10.1038/s41467-018-02942-5

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

Alison P. 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 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

Department of Paediatrics, Obstetrics and Gynaecology, and Preventive Medicine and Public Health

Research output: Contribution to journal › Article › Research

199 Citations (Scopus)

Abstract

© 2018 The Author(s). 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 language	English
Article number	556
Journal	Nature Communications
Volume	9
DOIs	https://doi.org/10.1038/s41467-018-02942-5
Publication status	Published - 1 Dec 2018

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Klein, A. P., Wolpin, B. M., Risch, H. A., Stolzenberg-Solomon, R. Z., Mocci, E., Zhang, M., Canzian, F., Childs, E. J., Hoskins, J. W., Jermusyk, A., Zhong, J., Chen, F., Albanes, D., Andreotti, G., Arslan, A. A., Babic, A., Bamlet, W. R., Beane-Freeman, L., Berndt, S. I., ... Soucek, P. (2018). Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer. Nature Communications, 9, Article 556. https://doi.org/10.1038/s41467-018-02942-5

@article{e77878a582064d979a8030f614a78c1e,

title = "Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer",

abstract = "{\textcopyright} 2018 The Author(s). 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.",

author = "Klein, {Alison P.} and Wolpin, {Brian M.} and Risch, {Harvey A.} and Stolzenberg-Solomon, {Rachael Z.} and Evelina Mocci and Mingfeng Zhang and Federico Canzian and Childs, {Erica J.} and Hoskins, {Jason W.} and Ashley Jermusyk and Jun Zhong and Fei Chen and Demetrius Albanes and Gabriella Andreotti and Arslan, {Alan A.} and Ana Babic and Bamlet, {William R.} and Laura Beane-Freeman and Berndt, {Sonja I.} and Amanda Blackford and Michael Borges and Ayelet Borgida and Bracci, {Paige M.} and Lauren Brais and Paul Brennan and Hermann Brenner and Bas Bueno-De-Mesquita and Julie Buring and Daniele Campa and Gabriele Capurso and Cavestro, {Giulia Martina} and Chaffee, {Kari G.} and Chung, {Charles C.} and Sean Cleary and Michelle Cotterchio and Frederike Dijk and Duell, {Eric J.} and Lenka Foretova and Charles Fuchs and Niccola Funel and Steven Gallinger and Gaziano, {J. Michael M.} and Maria Gazouli and Giles, {Graham G.} and Edward Giovannucci and Michael Goggins and Goodman, {Gary E.} and Goodman, {Phyllis J.} and Thilo Hackert and Christopher Haiman and Patricia Hartge and Manal Hasan and Peter Hegyi and Helzlsouer, {Kathy J.} and Joseph Herman and Ivana Holcatova and Holly, {Elizabeth A.} and Robert Hoover and Hung, {Rayjean J.} and Jacobs, {Eric J.} and Krzysztof Jamroziak and Vladimir Janout and Rudolf Kaaks and Khaw, {Kay Tee} and Klein, {Eric A.} and Manolis Kogevinas and Charles Kooperberg and Kulke, {Matthew H.} and Juozas Kupcinskas and Kurtz, {Robert J.} and Daniel Laheru and Stefano Landi and Lawlor, {Rita T.} and Lee, {I. Min} and Loic Lemarchand and Lingeng Lu and N{\'u}ria Malats and Andrea Mambrini and Satu Mannisto and Milne, {Roger L.} and Beatrice Moheln{\'i}kov{\'a}-Ducho{\v n}ov{\'a} and Neale, {Rachel E.} and Neoptolemos, {John P.} and Oberg, {Ann L.} and Olson, {Sara H.} and Irene Orlow and Claudio Pasquali and Patel, {Alpa V.} and Ulrike Peters and Raffaele Pezzilli and Miquel Porta and Real, {Francisco X.} and Nathaniel Rothman and Ghislaine Scelo and Sesso, {Howard D.} and Gianluca Severi and Shu, {Xiao Ou} and Debra Silverman and Smith, {Jill P.} and Pavel Soucek",

year = "2018",

month = dec,

day = "1",

doi = "10.1038/s41467-018-02942-5",

language = "English",

volume = "9",

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Klein, AP, 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, M, 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 2018, 'Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer', Nature Communications, vol. 9, 556. https://doi.org/10.1038/s41467-018-02942-5

TY - JOUR

T1 - Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer

AU - Klein, Alison P.

AU - Wolpin, Brian M.

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

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

PY - 2018/12/1

Y1 - 2018/12/1

N2 - © 2018 The Author(s). 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 - © 2018 The Author(s). 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.

U2 - 10.1038/s41467-018-02942-5

DO - 10.1038/s41467-018-02942-5

M3 - Article

C2 - 29422604

SN - 2041-1723

VL - 9

JO - Nature Communications

JF - Nature Communications

M1 - 556

ER -

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

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