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Common gene variants within 3'-untranslated regions as modulators of multiple myeloma risk and survival

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  • Ombretta Melaiu
  • Angelica Macauda
  • Juan Sainz
  • Diego Calvetti
  • Maria Sole Facioni
  • Giuseppe Maccari
  • Rob Ter Horst
  • Mihai G Netea
  • Yang Li
  • Norbert Grząśko
  • Victor Moreno
  • Artur Jurczyszyn
  • Andrés Jerez
  • Marzena Watek
  • Judit Varkonyi
  • Ramon Garcia-Sanz
  • Marcin Kruszewski
  • Marek Dudziński
  • Katalin Kadar
  • Svend Erik Hove Jacobsen
  • Grzegorz Mazur
  • Vibeke Andersen
  • Malwina Rybicka
  • Daria Zawirska
  • Malgorzata Raźny
  • Jan Maciej Zaucha
  • Olga Ostrovsky
  • Elzbieta Iskierka-Jazdzewska
  • Rui Manuel Reis
  • Anna Stępień
  • Katia Beider
  • Arnon Nagler
  • Agnieszka Druzd-Sitek
  • Herlander Marques
  • Joaquin Martìnez-Lopez
  • Fabienne Lesueur
  • Hervé Avet-Loiseau
  • Annette Juul Vangsted
  • Malgorzata Krawczyk-Kulis
  • Aleksandra Butrym
  • Krzysztof Jamroziak
  • Charles Dumontet
  • Ulla Vogel
  • Marcin Rymko
  • Matteo Pelosini
  • Edyta Subocz
  • Gergely Szombath
  • Maria Eugenia Sarasquete
  • Roberto Silvestri
  • Federica Morani
  • Stefano Landi
  • Daniele Campa
  • Federico Canzian
  • Federica Gemignani
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We evaluated the association between germline genetic variants located within the 3'-untranlsated region (polymorphic 3'UTR, ie, p3UTR) of candidate genes involved in multiple myeloma (MM). We performed a case-control study within the International Multiple Myeloma rESEarch (IMMEnSE) consortium, consisting of 3056 MM patients and 1960 controls recruited from eight countries. We selected p3UTR of six genes known to act in different pathways relevant in MM pathogenesis, namely KRAS (rs12587 and rs7973623), VEGFA (rs10434), SPP1 (rs1126772), IRF4 (rs12211228) and IL10 (rs3024496). We found that IL10-rs3024496 was associated with increased risk of developing MM and with a worse overall survival of MM patients. The variant allele was assayed in a vector expressing eGFP chimerized with the IL10 3'-UTR and it was found functionally active following transfection in human myeloma cells. In this experiment, the A-allele caused a lower expression of the reporter gene and this was also in agreement with the in vivo expression of mRNA measured in whole blood as reported in the GTEx portal. Overall, these data are suggestive of an effect of the IL10-rs3024496 SNP on the regulation of IL10 mRNA expression and it could have clinical implications for better characterization of MM patients in terms of prognosis.

Original languageEnglish
JournalInternational Journal of Cancer
Volume148
Issue number8
Pages (from-to)1887-1894
Number of pages8
ISSN0020-7136
DOIs
Publication statusPublished - 15 Apr 2021

    Research areas

  • 3′-untranslated region, multiple myeloma, overall survival, risk, single nucleotide polymorphisms, susceptibility, &#8208, 3&#8242, untranslated region

ID: 62328078