Premium
Genome‐wide association study identifies an early onset pancreatic cancer risk locus
Author(s) -
Campa Daniele,
Gentiluomo Manuel,
Obazee Ofure,
Ballerini Alba,
Vodickova Ludmila,
Hegyi Péter,
Soucek Pavel,
Brenner Hermann,
Milanetto Anna Caterina,
Landi Stefano,
Gao Xin,
Bozzato Dania,
Capurso Gabriele,
Tavano Francesca,
Vashist Yogesh,
Hackert Thilo,
Bambi Franco,
Bursi Simona,
Oliverius Martin,
Gioffreda Domenica,
Schöttker Ben,
Ivanauskas Audrius,
MohelnikovaDuchonova Beatrice,
Darvasi Erika,
Pezzilli Raffaele,
MałeckaPanas Ewa,
Strobel Oliver,
Gazouli Maria,
Katzke Verena,
Szentesi Andrea,
Cavestro Giulia Martina,
Farkas Gyula,
Izbicki Jakob R.,
Moz Stefania,
Archibugi Livia,
Hlavac Viktor,
Vincze Áron,
TalarWojnarowska Renata,
Rusev Borislav,
Kupcinskas Juozas,
Greenhalf Bill,
Dijk Frederike,
Giese Nathalia,
Boggi Ugo,
Andriulli Angelo,
Busch Olivier R,
Vanella Giuseppe,
Vodicka Pavel,
Nentwich Michael,
Lawlor Rita T.,
Theodoropoulos George E,
Jamroziak Krzysztof,
Zuppardo Raffaella Alessia,
Moletta Lucia,
Ginocchi Laura,
Kaaks Rudolf,
Neoptolemos John P,
Lucchesi Maurizio,
Canzian Federico
Publication year - 2020
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.33004
Subject(s) - genome wide association study , pancreatic cancer , single nucleotide polymorphism , genetic association , disease , in silico , locus (genetics) , biology , oncology , medicine , age of onset , cancer , genetics , gene , genotype
Early onset pancreatic cancer (EOPC) is a rare disease with a very high mortality rate. Almost nothing is known on the genetic susceptibility of EOPC, therefore, we performed a genome‐wide association study (GWAS) to identify novel genetic variants specific for patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) at younger ages. In the first phase, conducted on 821 cases with age of onset ≤60 years, of whom 198 with age of onset ≤50, and 3227 controls from PanScan I‐II, we observed four SNPs (rs7155613, rs2328991, rs4891017 and rs12610094) showing an association with EOPC risk ( P < 1 × 10 −4 ). We replicated these SNPs in the PANcreatic Disease ReseArch (PANDoRA) consortium and used additional in silico data from PanScan III and PanC4. Among these four variants rs2328991 was significant in an independent set of 855 cases with age of onset ≤60 years, of whom 265 with age of onset ≤50, and 4142 controls from the PANDoRA consortium while in the in silico data, we observed no statistically significant association. However, the resulting meta‐analysis supported the association ( P = 1.15 × 10 −4 ). In conclusion, we propose a novel variant rs2328991 to be involved in EOPC risk. Even though it was not possible to find a mechanistic link between the variant and the function, the association is supported by a solid statistical significance obtained in the largest study on EOPC genetics present so far in the literature.