Περίληψη:
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. © 2015 Nature America, Inc. All rights reserved.
Συγγραφείς:
Childs, E.J.
Mocci, E.
Campa, D.
Bracci, P.M.
Gallinger, S.
Goggins, M.
Li, D.
Neale, R.E.
Olson, S.H.
Scelo, G.
Amundadottir, L.T.
Bamlet, W.R.
Bijlsma, M.F.
Blackford, A.
Borges, M.
Brennan, P.
Brenner, H.
Bueno-De-Mesquita, H.B.
Canzian, F.
Capurso, G.
Cavestro, G.M.
Chaffee, K.G.
Chanock, S.J.
Cleary, S.P.
Cotterchio, M.
Foretova, L.
Fuchs, C.
Funel, N.
Gazouli, M.
Hassan, M.
Herman, J.M.
Holcatova, I.
Holly, E.A.
Hoover, R.N.
Hung, R.J.
Janout, V.
Key, T.J.
Kupcinskas, J.
Kurtz, R.C.
Landi, S.
Lu, L.
Malecka-Panas, E.
Mambrini, A.
Mohelnikova-Duchonova, B.
Neoptolemos, J.P.
Oberg, A.L.
Orlow, I.
Pasquali, C.
Pezzilli, R.
Rizzato, C.
Saldia, A.
Scarpa, A.
Stolzenberg-Solomon, R.Z.
Strobel, O.
Tavano, F.
Vashist, Y.K.
Vodicka, P.
Wolpin, B.M.
Yu, H.
Petersen, G.M.
Risch, H.A.
Klein, A.P.
Λέξεις-κλειδιά:
E1A associated p300 protein; hepatocyte nuclear factor 1; hepatocyte nuclear factor 3alpha; hepatocyte nuclear factor 3beta; protein; RAD21 protein; unclassified drug, Article; cancer risk; controlled study; gene linkage disequilibrium; gene locus; genetic association; genetic susceptibility; genetic variability; genotype; human; major clinical study; pancreas adenocarcinoma; pancreas cancer; phenotype; phenotypic variation; priority journal; quantitative trait locus; single nucleotide polymorphism; smoking; tissues; aged; Australia; chromosome 17; chromosome 2; chromosome 3; chromosome 7; clinical trial; Europe; female; gene frequency; genetic predisposition; genetics; male; middle aged; multicenter study; North America; pancreas tumor; procedures; risk factor; single nucleotide polymorphism, Aged; Australia; Chromosomes, Human, Pair 17; Chromosomes, Human, Pair 2; Chromosomes, Human, Pair 3; Chromosomes, Human, Pair 7; Europe; Female; Gene Frequency; Genetic Loci; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Humans; Male; Middle Aged; North America; Pancreatic Neoplasms; Polymorphism, Single Nucleotide; Risk Factors
