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 E. 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,Howard D. Sesso,Kala Visvanathan,Emily White,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 C. Chung,Michelle Cotterchio,Eithne Costello,Joanne W. Elena,Niccola Funel,J. Michael Gaziano,J. Michael Gaziano,J. Michael Gaziano,Nathalia Giese,Edward Giovannucci,Michael Goggins,Megan J. Gorman,Myron D. Gross,Christopher A. Haiman,Manal M. 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 Z. LaCroix,Maria Teresa Landi,Stefano Landi,Loic Le Marchand,Andrea Mambrini,Satu Männistö,Roger L. Milne,Yusuke Nakamura,Ann L. Oberg,Kouros Owzar,Alpa V. Patel,Petra H.M. Peeters,Petra H.M. Peeters,Ulrike Peters,Raffaele Pezzilli,Ada Piepoli,Miquel Porta,Miquel Porta,Francisco X. Real,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 Theodoropoulos,Mark D. 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 N. Hoover,Patricia Hartge,Charles S. Fuchs,Stephen J. Chanock,Rachael S. Stolzenberg-Solomon,Laufey T. Amundadottir +123 more
TLDR
This study identified multiple new susceptibility alleles for pancreatic cancer that are worthy of follow-up studies and an independent signal in exon 2 of TERT at the established region 5p15.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.read more
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A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33
Gloria M. Petersen,Laufey T. Amundadottir,Charles S. Fuchs,Peter Kraft,Rachael Z. Stolzenberg-Solomon,Kevin B. Jacobs,Kevin B. Jacobs,Alan A. Arslan,H. Bas Bueno-de-Mesquita,Steven Gallinger,Myron D. Gross,Kathy J. Helzlsouer,Elizabeth A. Holly,Eric J. Jacobs,Alison P. Klein,Andrea Z. LaCroix,Donghui Li,Margaret T. Mandelson,Sara H. Olson,Harvey A. Risch,Wei Zheng,Demetrius Albanes,William R. Bamlet,Christine D. Berg,Marie-Christine Boutron-Ruault,Julie E. Buring,Paige M. Bracci,Federico Canzian,Sandra Clipp,Michelle Cotterchio,Mariza de Andrade,Eric J. Duell,J. Michael Gaziano,J. Michael Gaziano,Edward Giovannucci,Michael Goggins,Göran Hallmans,Susan E. Hankinson,Manal Hassan,Barbara V. Howard,David J. Hunter,Amy K. Hutchinson,Amy K. Hutchinson,Mazda Jenab,Rudolf Kaaks,Charles Kooperberg,Vittorio Krogh,Robert C. Kurtz,Shannon M. Lynch,Robert R. McWilliams,Julie B. Mendelsohn,Dominique S. Michaud,Dominique S. Michaud,Hemang Parikh,Alpa V. Patel,Petra H.M. Peeters,Petra H.M. Peeters,Aleksandar Rajkovic,Elio Riboli,Laudina Rodríguez,Daniela Seminara,Xiao-Ou Shu,Gilles Thomas,Gilles Thomas,Anne Tjønneland,Geoffrey S. Tobias,Dimitrios Trichopoulos,Dimitrios Trichopoulos,Stephen K. Van Den Eeden,Jarmo Virtamo,Jean Wactawski-Wende,Zhaoming Wang,Zhaoming Wang,Brian M. Wolpin,Herbert Yu,Kai Yu,Anne Zeleniuch-Jacquotte,Joseph F. Fraumeni,Robert N. Hoover,Patricia Hartge,Stephen J. Chanock,Stephen J. Chanock,Stephen J. Chanock +82 more
TL;DR: This study has identified common susceptibility loci for pancreatic cancer that warrant follow-up studies and identified eight SNPs that map to three loci on chromosomes 13q22.1, 1q32.1 and 5p15.1 that are associated with multiple cancers.
Journal ArticleDOI
Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases A Mendelian Randomization Study
Philip C Haycock,Stephen Burgess,Aayah Nounu,Jie Zheng,G N Okoli,Jack Bowden,Kaitlin H Wade,Nicholas J. Timpson,David M. Evans,Peter Willeit,Abraham Aviv,Tom R. Gaunt,Gibran Hemani,Massimo Mangino,Hayley P Ellis,Kathreena M Kurian,Karen A. Pooley,Rosalind A. Eeles,Jeffrey E. Lee,Shenying Fang,Wei V. Chen,Matthew Law,Lisa Bowdler,Mark M. Iles,Qiong Yang,Bradford B. Worrall,Hugh S. Markus,Rayjean J. Hung,Christopher I. Amos,Amanda B. Spurdle,Deborah J. Thompson,Tracy A. O'Mara,Brian M. Wolpin,Laufey T. Amundadottir,Rachael Z. Stolzenberg-Solomon,Antonia Trichopoulou,N. Charlotte Onland-Moret,Eiliv Lund,Eric J. Duell,Federico Canzian,Gianluca Severi,Kim Overvad,Marc J. Gunter,Rosario Tumino,Ulrika Svenson,Andre M. van Rij,Annette F. Baas,Matthew J. Bown,Nilesh J. Samani,Femke N G van t'Hof,Gerard Tromp,Gregory T. Jones,Helena Kuivaniemi,James R. Elmore,Mattias Johansson,James McKay,Ghislaine Scelo,Robert Carreras-Torres,Valerie Gaborieau,Paul Brennan,Paige M. Bracci,Rachel E. Neale,Sara H. Olson,Steven Gallinger,Donghui Li,Gloria M. Petersen,Harvey A. Risch,Alison P. Klein,Jiali Han,Christian C. Abnet,Neal D. Freedman,Philip R. Taylor,John M. Maris,Katja K.H. Aben,Lambertus A. Kiemeney,Sita H. Vermeulen,John K. Wiencke,Kyle M. Walsh,Margaret Wrensch,Terri Rice,Clare Turnbull,Kevin Litchfield,Lavinia Paternoster,Marie Standl,Gonçalo R. Abecasis,John Paul SanGiovanni,Yong Li,Vladan Mijatovic,Yadav Sapkota,Siew-Kee Low,Krina T. Zondervan,Grant W. Montgomery,Dale R. Nyholt,David A. van Heel,Karen A. Hunt,Dan E. Arking,Foram N. Ashar,Nona Sotoodehnia,Daniel Woo,Jonathan Rosand,Mary E. Comeau,W. Mark Brown,Edwin K. Silverman,John E. Hokanson,Michael H. Cho,Jennie Hui,Manuel A. R. Ferreira,Philip J. Thompson,Alanna C. Morrison,Janine F. Felix,Nicholas L. Smith,Angela M. Christiano,Lynn Petukhova,Regina C. Betz,Xing Fan,Xuejun Zhang,Caihong Zhu,Carl D. Langefeld,Susan D. Thompson,Feijie Wang,Xu Lin,David A. Schwartz,Tasha E. Fingerlin,Jerome I. Rotter,Mary Frances Cotch,Richard A. Jensen,Matthias Munz,Henrik Dommisch,Arne S. Schaefer,Fang Han,Hanna Ollila,Ryan P. Hillary,Omar M. E. Albagha,Stuart H. Ralston,Chenjie Zeng,Wei Zheng,Xiao-Ou Shu,André Reis,Steffen Uebe,Ulrike Hüffmeier,Yoshiya Kawamura,Takeshi Otowa,Tsukasa Sasaki,Martin L. Hibberd,Sonia Davila,Gang Xie,Katherine A. Siminovitch,Jin-Xin Bei,Yi Xin Zeng,Asta Försti,Bowang Chen,Stefano Landi,Andre Franke,Annegret Fischer,David Ellinghaus,Carlos Flores,Imre Noth,Shwu-Fan Ma,Jia Nee Foo,Jianjun Liu,Jong-Won Kim,David G. Cox,Olivier Delattre,Olivier Mirabeau,Christine F. Skibola,Clara S. Tang,Merce Garcia-Barcelo,Kai-Ping Chang,Wen-Hui Su,Yu-Sun Chang,Nicholas G. Martin,Scott D. Gordon,Tracey D. Wade,Chaeyoung Lee,Michiaki Kubo,Pei-Chieng Cha,Yusuke Nakamura,Daniel Levy,Masayuki Kimura,Shih-Jen Hwang,Steven C. Hunt,Tim D. Spector,Nicole Soranzo,Ani Manichaikul,R. Graham Barr,Bratati Kahali,Elizabeth K. Speliotes,Laura M. Yerges-Armstrong,Ching-Yu Cheng,Jost B. Jonas,Tien Yin Wong,Isabella Fogh,Kuang Lin,John Powell,Kenneth Rice,Caroline L Relton,Richard M. Martin,George Davey Smith +197 more
TL;DR: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases, as well as single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population.
Journal ArticleDOI
Pancreatic cancer biology and genetics from an evolutionary perspective
TL;DR: The wide-ranging aspects of pancreatic cancer research are gathered into a single concept rooted in Darwinian evolution, with the goal of identifying novel insights and opportunities for study.
Journal ArticleDOI
Genome-wide association studies of cancer: current insights and future perspectives
TL;DR: Genome-wide association studies have shown that common genetic variation contributes substantially to the heritable risk of many common cancers, and deciphering the functional and biological basis of associations is challenging and is in part a barrier to fully unlocking the potential of GWAS.
Book ChapterDOI
Epidemiology of pancreatic cancer
TL;DR: This article found that periodontal infection and gastric ulcers may increase the risk of pancreatic cancer, while allergies may decrease risk, but few observational studies have had tumor tissue to address these questions.
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A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33
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