Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer

Erica J. Childs, Evelina Mocci, Daniele Campa, Paige M. Bracci, Steven Gallinger, Michael S Goggins, Donghui Li, Rachel E. Neale, Sara H. Olson, Ghislaine Scelo, Laufey T. Amundadottir, William R. Bamlet, Maarten F. Bijlsma, Amanda Blackford, Michael Borges, Paul Brennan, Hermann Brenner, H. Bas Bueno-De-Mesquita, Federico Canzian, Gabriele CapursoGiulia M. Cavestro, Kari G. Chaffee, Stephen J. Chanock, Sean P. Cleary, Michelle Cotterchio, Lenka Foretova, Charles Fuchs, Niccola Funel, Maria Gazouli, Manal Hassan, Joseph M. Herman, Ivana Holcatova, Elizabeth A. Holly, Robert N. Hoover, Rayjean J. Hung, Vladimir Janout, Timothy J. Key, Juozas Kupcinskas, Robert C. Kurtz, Stefano Landi, Lingeng Lu, Ewa Malecka-Panas, Andrea Mambrini, Beatrice Mohelnikova-Duchonova, John P. Neoptolemos, Ann L. Oberg, Irene Orlow, Claudio Pasquali, Raffaele Pezzilli, Cosmeri Rizzato, Amethyst Saldia, Aldo Scarpa, Rachael Z. Stolzenberg-Solomon, Oliver Strobel, Francesca Tavano, Yogesh K. Vashist, Pavel Vodicka, Brian M. Wolpin, Herbert Yu, Gloria M. Petersen, Harvey A. Risch, Alison Klein

Research output: Contribution to journalArticle

Abstract

Pancreatic cancer is the fourth leading cause of cancer death in the developed world. Both inherited high-penetrance mutations in BRCA2 (ref. 2), ATM, PALB2 (ref. 4), BRCA1 (ref. 5), STK11 (ref. 6), CDKN2A and mismatch-repair genes and low-penetrance loci are associated with increased risk. To identify new risk loci, we performed a genome-wide association study on 9,925 pancreatic cancer cases and 11,569 controls, including 4,164 newly genotyped cases and 3,792 controls in 9 studies from North America, Central Europe and Australia. We identified three newly associated regions: 17q25.1 (LINC00673, rs11655237, odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.19-1.34, P = 1.42 × 10-14), 7p13 (SUGCT, rs17688601, OR = 0.88, 95% CI = 0.84-0.92, P = 1.41 × 10-8) and 3q29 (TP63, rs9854771, OR = 0.89, 95% CI = 0.85-0.93, P = 2.35 × 10-8). We detected significant association at 2p13.3 (ETAA1, rs1486134, OR = 1.14, 95% CI = 1.09-1.19, P = 3.36 × 10-9), a region with previous suggestive evidence in Han Chinese. We replicated previously reported associations at 9q34.2 (ABO), 13q22.1 (KLF5), 5p15.33 (TERT and CLPTM1), 13q12.2 (PDX1), 1q32.1 (NR5A2), 7q32.3 (LINC-PINT), 16q23.1 (BCAR1) and 22q12.1 (ZNRF3). Our study identifies new loci associated with pancreatic cancer risk.

Original languageEnglish (US)
Pages (from-to)911-916
Number of pages6
JournalNature Genetics
Volume47
Issue number8
DOIs
StatePublished - Aug 30 2015

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Pancreatic Neoplasms
Odds Ratio
Confidence Intervals
Penetrance
DNA Mismatch Repair
Genome-Wide Association Study
North America
Cause of Death
Mutation
Genes
Neoplasms

ASJC Scopus subject areas

  • Genetics

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Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer. / Childs, Erica J.; Mocci, Evelina; Campa, Daniele; Bracci, Paige M.; Gallinger, Steven; Goggins, Michael S; Li, Donghui; Neale, Rachel E.; Olson, Sara H.; Scelo, Ghislaine; Amundadottir, Laufey T.; Bamlet, William R.; Bijlsma, Maarten F.; Blackford, Amanda; Borges, Michael; Brennan, Paul; Brenner, Hermann; Bueno-De-Mesquita, H. Bas; Canzian, Federico; Capurso, Gabriele; Cavestro, Giulia M.; Chaffee, Kari G.; Chanock, Stephen J.; Cleary, Sean P.; Cotterchio, Michelle; Foretova, Lenka; Fuchs, Charles; Funel, Niccola; Gazouli, Maria; Hassan, Manal; Herman, Joseph M.; Holcatova, Ivana; Holly, Elizabeth A.; Hoover, Robert N.; Hung, Rayjean J.; Janout, Vladimir; Key, Timothy J.; Kupcinskas, Juozas; Kurtz, Robert C.; Landi, Stefano; Lu, Lingeng; Malecka-Panas, Ewa; Mambrini, Andrea; Mohelnikova-Duchonova, Beatrice; Neoptolemos, John P.; Oberg, Ann L.; Orlow, Irene; Pasquali, Claudio; Pezzilli, Raffaele; Rizzato, Cosmeri; Saldia, Amethyst; Scarpa, Aldo; Stolzenberg-Solomon, Rachael Z.; Strobel, Oliver; Tavano, Francesca; Vashist, Yogesh K.; Vodicka, Pavel; Wolpin, Brian M.; Yu, Herbert; Petersen, Gloria M.; Risch, Harvey A.; Klein, Alison.

In: Nature Genetics, Vol. 47, No. 8, 30.08.2015, p. 911-916.

Research output: Contribution to journalArticle

Childs, EJ, Mocci, E, Campa, D, Bracci, PM, Gallinger, S, Goggins, MS, Li, D, Neale, RE, Olson, SH, Scelo, G, Amundadottir, LT, Bamlet, WR, Bijlsma, MF, Blackford, A, Borges, M, Brennan, P, Brenner, H, Bueno-De-Mesquita, HB, Canzian, F, Capurso, G, Cavestro, GM, Chaffee, KG, Chanock, SJ, Cleary, SP, Cotterchio, M, Foretova, L, Fuchs, C, Funel, N, Gazouli, M, Hassan, M, Herman, JM, Holcatova, I, Holly, EA, Hoover, RN, Hung, RJ, Janout, V, Key, TJ, Kupcinskas, J, Kurtz, RC, Landi, S, Lu, L, Malecka-Panas, E, Mambrini, A, Mohelnikova-Duchonova, B, Neoptolemos, JP, Oberg, AL, Orlow, I, Pasquali, C, Pezzilli, R, Rizzato, C, Saldia, A, Scarpa, A, Stolzenberg-Solomon, RZ, Strobel, O, Tavano, F, Vashist, YK, Vodicka, P, Wolpin, BM, Yu, H, Petersen, GM, Risch, HA & Klein, A 2015, 'Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer', Nature Genetics, vol. 47, no. 8, pp. 911-916. https://doi.org/10.1038/ng.3341
Childs, Erica J. ; Mocci, Evelina ; Campa, Daniele ; Bracci, Paige M. ; Gallinger, Steven ; Goggins, Michael S ; Li, Donghui ; Neale, Rachel E. ; Olson, Sara H. ; Scelo, Ghislaine ; Amundadottir, Laufey T. ; Bamlet, William R. ; Bijlsma, Maarten F. ; Blackford, Amanda ; Borges, Michael ; Brennan, Paul ; Brenner, Hermann ; Bueno-De-Mesquita, H. Bas ; Canzian, Federico ; Capurso, Gabriele ; Cavestro, Giulia M. ; Chaffee, Kari G. ; Chanock, Stephen J. ; Cleary, Sean P. ; Cotterchio, Michelle ; Foretova, Lenka ; Fuchs, Charles ; Funel, Niccola ; Gazouli, Maria ; Hassan, Manal ; Herman, Joseph M. ; Holcatova, Ivana ; Holly, Elizabeth A. ; Hoover, Robert N. ; Hung, Rayjean J. ; Janout, Vladimir ; Key, Timothy J. ; Kupcinskas, Juozas ; Kurtz, Robert C. ; Landi, Stefano ; Lu, Lingeng ; Malecka-Panas, Ewa ; Mambrini, Andrea ; Mohelnikova-Duchonova, Beatrice ; Neoptolemos, John P. ; Oberg, Ann L. ; Orlow, Irene ; Pasquali, Claudio ; Pezzilli, Raffaele ; Rizzato, Cosmeri ; Saldia, Amethyst ; Scarpa, Aldo ; Stolzenberg-Solomon, Rachael Z. ; Strobel, Oliver ; Tavano, Francesca ; Vashist, Yogesh K. ; Vodicka, Pavel ; Wolpin, Brian M. ; Yu, Herbert ; Petersen, Gloria M. ; Risch, Harvey A. ; Klein, Alison. / Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer. In: Nature Genetics. 2015 ; Vol. 47, No. 8. pp. 911-916.
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title = "Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer",
abstract = "Pancreatic cancer is the fourth leading cause of cancer death in the developed world. Both inherited high-penetrance mutations in BRCA2 (ref. 2), ATM, PALB2 (ref. 4), BRCA1 (ref. 5), STK11 (ref. 6), CDKN2A and mismatch-repair genes and low-penetrance loci are associated with increased risk. To identify new risk loci, we performed a genome-wide association study on 9,925 pancreatic cancer cases and 11,569 controls, including 4,164 newly genotyped cases and 3,792 controls in 9 studies from North America, Central Europe and Australia. We identified three newly associated regions: 17q25.1 (LINC00673, rs11655237, odds ratio (OR) = 1.26, 95{\%} confidence interval (CI) = 1.19-1.34, P = 1.42 × 10-14), 7p13 (SUGCT, rs17688601, OR = 0.88, 95{\%} CI = 0.84-0.92, P = 1.41 × 10-8) and 3q29 (TP63, rs9854771, OR = 0.89, 95{\%} CI = 0.85-0.93, P = 2.35 × 10-8). We detected significant association at 2p13.3 (ETAA1, rs1486134, OR = 1.14, 95{\%} CI = 1.09-1.19, P = 3.36 × 10-9), a region with previous suggestive evidence in Han Chinese. We replicated previously reported associations at 9q34.2 (ABO), 13q22.1 (KLF5), 5p15.33 (TERT and CLPTM1), 13q12.2 (PDX1), 1q32.1 (NR5A2), 7q32.3 (LINC-PINT), 16q23.1 (BCAR1) and 22q12.1 (ZNRF3). Our study identifies new loci associated with pancreatic cancer risk.",
author = "Childs, {Erica J.} and Evelina Mocci and Daniele Campa and Bracci, {Paige M.} and Steven Gallinger and Goggins, {Michael S} and Donghui Li and Neale, {Rachel E.} and Olson, {Sara H.} and Ghislaine Scelo and Amundadottir, {Laufey T.} and Bamlet, {William R.} and Bijlsma, {Maarten F.} and Amanda Blackford and Michael Borges and Paul Brennan and Hermann Brenner and Bueno-De-Mesquita, {H. Bas} and Federico Canzian and Gabriele Capurso and Cavestro, {Giulia M.} and Chaffee, {Kari G.} and Chanock, {Stephen J.} and Cleary, {Sean P.} and Michelle Cotterchio and Lenka Foretova and Charles Fuchs and Niccola Funel and Maria Gazouli and Manal Hassan and Herman, {Joseph M.} and Ivana Holcatova and Holly, {Elizabeth A.} and Hoover, {Robert N.} and Hung, {Rayjean J.} and Vladimir Janout and Key, {Timothy J.} and Juozas Kupcinskas and Kurtz, {Robert C.} and Stefano Landi and Lingeng Lu and Ewa Malecka-Panas and Andrea Mambrini and Beatrice Mohelnikova-Duchonova and Neoptolemos, {John P.} and Oberg, {Ann L.} and Irene Orlow and Claudio Pasquali and Raffaele Pezzilli and Cosmeri Rizzato and Amethyst Saldia and Aldo Scarpa and Stolzenberg-Solomon, {Rachael Z.} and Oliver Strobel and Francesca Tavano and Vashist, {Yogesh K.} and Pavel Vodicka and Wolpin, {Brian M.} and Herbert Yu and Petersen, {Gloria M.} and Risch, {Harvey A.} and Alison Klein",
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T1 - Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer

AU - Childs, Erica J.

AU - Mocci, Evelina

AU - Campa, Daniele

AU - Bracci, Paige M.

AU - Gallinger, Steven

AU - Goggins, Michael S

AU - Li, Donghui

AU - Neale, Rachel E.

AU - Olson, Sara H.

AU - Scelo, Ghislaine

AU - Amundadottir, Laufey T.

AU - Bamlet, William R.

AU - Bijlsma, Maarten F.

AU - Blackford, Amanda

AU - Borges, Michael

AU - Brennan, Paul

AU - Brenner, Hermann

AU - Bueno-De-Mesquita, H. Bas

AU - Canzian, Federico

AU - Capurso, Gabriele

AU - Cavestro, Giulia M.

AU - Chaffee, Kari G.

AU - Chanock, Stephen J.

AU - Cleary, Sean P.

AU - Cotterchio, Michelle

AU - Foretova, Lenka

AU - Fuchs, Charles

AU - Funel, Niccola

AU - Gazouli, Maria

AU - Hassan, Manal

AU - Herman, Joseph M.

AU - Holcatova, Ivana

AU - Holly, Elizabeth A.

AU - Hoover, Robert N.

AU - Hung, Rayjean J.

AU - Janout, Vladimir

AU - Key, Timothy J.

AU - Kupcinskas, Juozas

AU - Kurtz, Robert C.

AU - Landi, Stefano

AU - Lu, Lingeng

AU - Malecka-Panas, Ewa

AU - Mambrini, Andrea

AU - Mohelnikova-Duchonova, Beatrice

AU - Neoptolemos, John P.

AU - Oberg, Ann L.

AU - Orlow, Irene

AU - Pasquali, Claudio

AU - Pezzilli, Raffaele

AU - Rizzato, Cosmeri

AU - Saldia, Amethyst

AU - Scarpa, Aldo

AU - Stolzenberg-Solomon, Rachael Z.

AU - Strobel, Oliver

AU - Tavano, Francesca

AU - Vashist, Yogesh K.

AU - Vodicka, Pavel

AU - Wolpin, Brian M.

AU - Yu, Herbert

AU - Petersen, Gloria M.

AU - Risch, Harvey A.

AU - Klein, Alison

PY - 2015/8/30

Y1 - 2015/8/30

N2 - Pancreatic cancer is the fourth leading cause of cancer death in the developed world. Both inherited high-penetrance mutations in BRCA2 (ref. 2), ATM, PALB2 (ref. 4), BRCA1 (ref. 5), STK11 (ref. 6), CDKN2A and mismatch-repair genes and low-penetrance loci are associated with increased risk. To identify new risk loci, we performed a genome-wide association study on 9,925 pancreatic cancer cases and 11,569 controls, including 4,164 newly genotyped cases and 3,792 controls in 9 studies from North America, Central Europe and Australia. We identified three newly associated regions: 17q25.1 (LINC00673, rs11655237, odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.19-1.34, P = 1.42 × 10-14), 7p13 (SUGCT, rs17688601, OR = 0.88, 95% CI = 0.84-0.92, P = 1.41 × 10-8) and 3q29 (TP63, rs9854771, OR = 0.89, 95% CI = 0.85-0.93, P = 2.35 × 10-8). We detected significant association at 2p13.3 (ETAA1, rs1486134, OR = 1.14, 95% CI = 1.09-1.19, P = 3.36 × 10-9), a region with previous suggestive evidence in Han Chinese. We replicated previously reported associations at 9q34.2 (ABO), 13q22.1 (KLF5), 5p15.33 (TERT and CLPTM1), 13q12.2 (PDX1), 1q32.1 (NR5A2), 7q32.3 (LINC-PINT), 16q23.1 (BCAR1) and 22q12.1 (ZNRF3). Our study identifies new loci associated with pancreatic cancer risk.

AB - Pancreatic cancer is the fourth leading cause of cancer death in the developed world. Both inherited high-penetrance mutations in BRCA2 (ref. 2), ATM, PALB2 (ref. 4), BRCA1 (ref. 5), STK11 (ref. 6), CDKN2A and mismatch-repair genes and low-penetrance loci are associated with increased risk. To identify new risk loci, we performed a genome-wide association study on 9,925 pancreatic cancer cases and 11,569 controls, including 4,164 newly genotyped cases and 3,792 controls in 9 studies from North America, Central Europe and Australia. We identified three newly associated regions: 17q25.1 (LINC00673, rs11655237, odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.19-1.34, P = 1.42 × 10-14), 7p13 (SUGCT, rs17688601, OR = 0.88, 95% CI = 0.84-0.92, P = 1.41 × 10-8) and 3q29 (TP63, rs9854771, OR = 0.89, 95% CI = 0.85-0.93, P = 2.35 × 10-8). We detected significant association at 2p13.3 (ETAA1, rs1486134, OR = 1.14, 95% CI = 1.09-1.19, P = 3.36 × 10-9), a region with previous suggestive evidence in Han Chinese. We replicated previously reported associations at 9q34.2 (ABO), 13q22.1 (KLF5), 5p15.33 (TERT and CLPTM1), 13q12.2 (PDX1), 1q32.1 (NR5A2), 7q32.3 (LINC-PINT), 16q23.1 (BCAR1) and 22q12.1 (ZNRF3). Our study identifies new loci associated with pancreatic cancer risk.

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