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

0451945 - ÚEM 2016 RIV US eng J - Článek v odborném periodiku
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. - Foretová, L. - Fuchs, Ch. - Funel, N. - Gazouli, M. - Hassan, M. - Herman, J.M. - Holcatová, I. - Holly, E. A. - Hoover, R.N. - Hung, R.J. - Janout, V. - Key, T.J. - Kupcinskas, J. - Kurtz, R. C. - Landi, S. - Lu, S. - Malecka-Panas, E. - Mambrini, A. - Mohelníková-Duchoňová, B. - Neoptolemos, J.P. - Oberg, A. L. - Orlow, I. - Pasquali, C. - Pezzilli, R. - Rizzato, C. - Saldia, A. - Scarpa, A. - Stolzenberg-Solomon, R. S. - Strobel, O. - Tavano, F. - Vashist, Y.K. - Vodička, Pavel - Wolpin, B. M. - Yu, H. - Petersen, G. - Risch, H. A. - Klein, A. P.
Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer.
Nature Genetics. Roč. 47, č. 8 (2015), s. 911-918. ISSN 1061-4036. E-ISSN 1546-1718
Grant CEP: GA MZd NR9422; GA ČR GAP301/12/1734
Institucionální podpora: RVO:68378041
Klíčová slova: genome-wide association * genotype imputation * lung adenocarcinoma * cigarette-smoking * genetic-variation * alpha-gene * risk * loci * population * mutations
Kód oboru RIV: EB - Genetika a molekulární biologie
Impakt faktor: 31.616, rok: 2015

Pancreatic cancer is the fourth leading cause of cancer death in the developed world(1). Both inherited high-penetrance mutations in BRCA2 (ref. 2), ATM(3), PALB2 (ref. 4), BRCA1 (ref. 5), STK11 (ref. 6), CDKN2A(7) and mismatch-repair genes(8) and low-penetrance loci are associated with increased risk(9-12). 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 x 10(-14)), 7p13 (SUGCT, rs17688601, OR = 0.88, 95% CI = 0.84-0.92, P = 1.41 x 10(-8)) and 3q29 (TP63, rs9854771, OR = 0.89, 95% CI = 0.85-0.93, P = 2.35 x 10(-8)). We detected significant association at 2p13.3 (ETAA1, rs1486134, OR = 1.14, 95% CI = 1.09-1.19, P = 3.36 x 10(-9)), a region with previous suggestive evidence in Han Chinese(12). We replicated previously reported associations at 9q34.2 (ABO)(9), 13q22.1 (KLF5)(10), 5p15.33 (TERT and CLPTM1)(10,11), 13q12.2 (PDX1)(11), 1q32.1 (NR5A2)(10), 7q32.3 (LINC-PINT)(11), 16q23.1 (BCAR1)(11) and 22q12.1 (ZNRF3)(11). Our study identifies new loci associated with pancreatic cancer risk.
Trvalý link: http://hdl.handle.net/11104/0253105