Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer.

Klein AP1,2, Wolpin BM3, Risch HA4, Stolzenberg-Solomon RZ5, Mocci E6, Zhang M7, Canzian F8, Childs EJ6, Hoskins JW7, Jermusyk A7, Zhong J7, Chen F6, Albanes D5, Andreotti G5, Arslan AA9,10,11, Babic A3, Bamlet WR12, Beane-Freeman L5, Berndt SI5, Blackford A6, Borges M13, Borgida A14, Bracci PM15, Brais L3, Brennan P16, Brenner H17,18,19, Bueno-de-Mesquita B20,21,22,23, Buring J24,25, Campa D26, Capurso G27, Cavestro GM28, Chaffee KG12, Chung CC5,29, Cleary S14, Cotterchio M30,31, Dijk F32, Duell EJ33, Foretova L34, Fuchs C35, Funel N36, Gallinger S14, M Gaziano JM37,38, Gazouli M39, Giles GG40,41,42, Giovannucci E3, Goggins M13, Goodman GE43, Goodman PJ44, Hackert T45, Haiman C46, Hartge P5, Hasan M47, Hegyi P48, Helzlsouer KJ49, Herman J50, Holcatova I51, Holly EA15, Hoover R5, Hung RJ14, Jacobs EJ52, Jamroziak K53, Janout V54,55, Kaaks R56, Khaw KT57, Klein EA58, Kogevinas M59,60,61,62, Kooperberg C43, Kulke MH3, Kupcinskas J63, Kurtz RJ64, Laheru D6, Landi S26, Lawlor RT65, Lee IM24,66, LeMarchand L67, Lu L4, Malats N68,69, Mambrini A70, Mannisto S71, Milne RL40,41, Mohelníková-Duchoňová B72, Neale RE73, Neoptolemos JP74, Oberg AL12, Olson SH75, Orlow I75, Pasquali C76, Patel AV52, Peters U43, Pezzilli R77, Porta M60,61, Real FX69,78,79, Rothman N5, Scelo G16, Sesso HD24,25, Severi G40,41,80, Shu XO81, Silverman D5, Smith JP82, Soucek P83, Sund M84, Talar-Wojnarowska R85, Tavano F86, Thornquist MD43, Tobias GS5, Van Den Eeden SK87, Vashist Y88, Visvanathan K89, Vodicka P90, Wactawski-Wende J91, Wang Z92, Wentzensen N5, White E43,93, Yu H67, Yu K5, Zeleniuch-Jacquotte A10,94, Zheng W81, Kraft P25,95, Li D96, Chanock S5, Obazee O8, Petersen GM12, Amundadottir LT97.

Author information

Abstract

In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 × 10-8). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 × 10-14), rs2941471 at 8q21.11 (HNF4G, P = 6.60 × 10-10), rs4795218 at 17q12 (HNF1B, P = 1.32 × 10-8), and rs1517037 at 18q21.32 (GRP, P = 3.28 × 10-8). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene.