Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer
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Publication date
2015-08-30
Authors
Childs, Erica J
Mocci, Evelina
Campa, Daniele
Bracci, Paige M
Gallinger, Steven
Goggins, Michael
Li, Donghui
Neale, Rachel E
Olson, Sara H
Scelo, Ghislaine
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Document Type
Letter
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taverne
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.
Keywords
Taverne, Genetics
Citation
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 2015, 'Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer', Nature Genetics, vol. 47, no. 8, pp. 911-916. https://doi.org/10.1038/ng.3341