Common gene variants within 3′-untranslated regions as modulators of multiple myeloma risk and survival [Epub ahead of print]

Tidsskriftartikel - 2020

Resume

Abstract We evaluated the association between germline genetic variants located within the 3'untranlsated region (polymorphic 3'UTR, that is, 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 8 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.

Reference

Melaiu O, Macauda A, Sainz J, Calvetti D, Facioni MS, Maccari G, ter Horst R, Netea MG, Li Y, GrzĄŚko N, Moreno V, Jurczyszyn A, Jerez A, Watek M, Varkonyi J, Garcia-Sanz R, Kruszewski M, DudziŃski M, Kadar K, Jacobsen SEH, Mazur G, Andersen V, Rybicka M, Zawirska D, RaŹny M, Zaucha JM, Ostrovsky O, Iskierka-Jazdzewska E, Reis RM, StĘpieŃ A, Beider K, Nagler A, Druzd-Sitek A, Marques H, Martìnez-Lopez J, Lesueur F, Avet-Loiseau H, Vangsted AJ, Krawczyk-Kulis M, Butrym A, Jamroziak K, Dumontet C, Vogel U, Rymko M, Pelosini M, Subocz E, Szombath G, Sarasquete ME, Silvestri R, Morani F, Landi S, Campa D, Canzian F, Gemignani F. Common gene variants within 3′-untranslated regions as modulators of multiple myeloma risk and survival [Epub ahead of print]. Int J Cancer 2020.
doi: 10.1002/ijc.33377

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