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 | |
| State | Published - 2014 |
ASJC Scopus subject areas
- Genetics
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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 journal › Article › peer-review
}
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.
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.
UR - http://www.scopus.com/inward/record.url?scp=84938423709&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84938423709&partnerID=8YFLogxK
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 -