A pleiotropic variant in DNAJB4 is associated with multiple myeloma risk

Research output: Contribution to journalJournal articleResearchpeer-review

Documents

  • Fulltext

    Final published version, 869 KB, PDF document

  • Marco Dicanio
  • Matteo Giaccherini
  • Alyssa Clay-Gilmour
  • Angelica Macauda
  • Juan Sainz
  • Mitchell J. Machiela
  • Malwina Rybicka-Ramos
  • Aaron D. Norman
  • Agata Tyczyńska
  • Stephen J. Chanock
  • Torben Barington
  • Shaji K. Kumar
  • Parveen Bhatti
  • Wendy Cozen
  • Elizabeth E. Brown
  • Anna Suska
  • Eva K. Haastrup
  • Robert Z. Orlowski
  • Marek Dudziński
  • Ramon Garcia-Sanz
  • Marcin Kruszewski
  • Joaquin Martinez-Lopez
  • Katia Beider
  • Elżbieta Iskierka-Jazdzewska
  • Matteo Pelosini
  • Sonja I. Berndt
  • Małgorzata Raźny
  • Krzysztof Jamroziak
  • S. Vincent Rajkumar
  • Artur Jurczyszyn
  • Pilar Garrido Collado
  • Ulla Vogel
  • Jonathan N. Hofmann
  • Mario Petrini
  • Aleksandra Butrym
  • Susan L. Slager
  • Elad Ziv
  • Edyta Subocz
  • Graham G. Giles
  • Niels Frost Andersen
  • Grzegorz Mazur
  • Marzena Watek
  • Fabienne Lesueur
  • Michelle A.T. Hildebrandt
  • Daria Zawirska
  • Lene Hyldahl Ebbesen
  • Herlander Marques
  • Federica Gemignani
  • Charles Dumontet
  • Judit Várkonyi
  • Gabriele Buda
  • Arnon Nagler
  • Agnieszka Druzd-Sitek
  • Xifeng Wu
  • Katalin Kadar
  • Nicola J. Camp
  • Norbert Grzasko
  • Rosalie G. Waller
  • Celine Vachon
  • Federico Canzian
  • Daniele Campa

Pleiotropy, which consists of a single gene or allelic variant affecting multiple unrelated traits, is common across cancers, with evidence for genome-wide significant loci shared across cancer and noncancer traits. This feature is particularly relevant in multiple myeloma (MM) because several susceptibility loci that have been identified to date are pleiotropic. Therefore, the aim of this study was to identify novel pleiotropic variants involved in MM risk using 28 684 independent single nucleotide polymorphisms (SNPs) from GWAS Catalog that reached a significant association (P < 5 × 10−8) with their respective trait. The selected SNPs were analyzed in 2434 MM cases and 3446 controls from the International Lymphoma Epidemiology Consortium (InterLymph). The 10 SNPs showing the strongest associations with MM risk in InterLymph were selected for replication in an independent set of 1955 MM cases and 1549 controls from the International Multiple Myeloma rESEarch (IMMEnSE) consortium and 418 MM cases and 147 282 controls from the FinnGen project. The combined analysis of the three studies identified an association between DNAJB4-rs34517439-A and an increased risk of developing MM (OR = 1.22, 95%CI 1.13-1.32, P = 4.81 × 10−7). rs34517439-A is associated with a modified expression of the FUBP1 gene, which encodes a multifunctional DNA and RNA-binding protein that it was observed to influence the regulation of various genes involved in cell cycle regulation, among which various oncogenes and oncosuppressors. In conclusion, with a pleiotropic scan approach we identified DNAJB4-rs34517439 as a potentially novel MM risk locus.

Original languageEnglish
JournalInternational Journal of Cancer
Volume152
Issue number2
Pages (from-to)239-248
Number of pages10
ISSN0020-7136
DOIs
Publication statusPublished - 2023

Bibliographical note

Publisher Copyright:
© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

    Research areas

  • genetic susceptibility, multiple myeloma, pleiotropy, pleiotropy scan, polymorphisms

ID: 334005368