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.
