Common gene variants within 3'-untranslated regions as modulators of multiple myeloma risk and survival.
3' Untranslated Regions
/ genetics
Adult
Aged
Case-Control Studies
Female
Gene Expression Regulation, Neoplastic
Gene Frequency
Genetic Predisposition to Disease
/ genetics
Genotype
Germ-Line Mutation
Humans
Male
Middle Aged
Multiple Myeloma
/ diagnosis
Polymorphism, Single Nucleotide
RNA, Messenger
/ genetics
Risk Factors
Survival Analysis
3′-untranslated region
multiple myeloma
overall survival
risk
single nucleotide polymorphisms
susceptibility
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
15 04 2021
15 04 2021
Historique:
received:
18
05
2020
revised:
04
08
2020
accepted:
07
08
2020
pubmed:
6
11
2020
medline:
3
8
2021
entrez:
5
11
2020
Statut:
ppublish
Résumé
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.
Substances chimiques
3' Untranslated Regions
0
RNA, Messenger
0
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1887-1894Informations de copyright
© 2020 Union for International Cancer Control.
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