Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer Journal Article
| Authors: | 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. |
| Article 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. © 2015 Nature America, Inc. All rights reserved. |
| Keywords: | controlled study; unclassified drug; major clinical study; single nucleotide polymorphism; cancer risk; pancreas cancer; phenotype; hepatocyte nuclear factor 3alpha; protein; gene locus; genetic association; genetic variability; genotype; smoking; genetic susceptibility; pancreas adenocarcinoma; phenotypic variation; quantitative trait locus; tissues; e1a associated p300 protein; hepatocyte nuclear factor 3beta; gene linkage disequilibrium; hepatocyte nuclear factor 1; human; priority journal; article; rad21 protein |
| Journal Title: | Nature Genetics |
| Volume: | 47 |
| Issue: | 8 |
| ISSN: | 1061-4036 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2015-08-01 |
| Start Page: | 911 |
| End Page: | 916 |
| Language: | English |
| DOI: | 10.1038/ng.3341 |
| PROVIDER: | scopus |
| PMCID: | PMC4520746 |
| PUBMED: | 26098869 |
| DOI/URL: | |
| Notes: | Export Date: 2 September 2015 -- Source: Scopus |
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