The International Multiple Myeloma Research (IMMEnSE) Consortium: Genetics of Multiple Myeloma Risk and Prognosis

We established the IMMEnSE (International Multiple Myeloma rESEarch) consortium, to increase our understanding of the genetic determinants of multiple myeloma (MM) risk, response to therapy and survival. At present we have DNA samples of over 3200 MM cases and 3000 healthy controls from 10 countries, mainly in Europe. For the majority of the cases clinical data on known prognostic factors, therapy outcome and survival have been also collected.

We already performed several association studies in the context of the IMMEnSE consortium. In particular, associations were found between MM risk and SNPs in the ABCB1 gene, which encodes for an efflux pump that has a key role in protecting cells from chemical damage (rs10264990: odds ratio (OR) =0.79, 95% confidence interval (CI) 0.68-0.91; p=0.001, and rs17327442: OR=1.99; 95%CI 1.32-3.02; p=0.001). We also investigated the 8q24 region, which has been shown to harbor multiple loci of susceptibility to various cancers, and found an association between a SNP mapping in this region and MM risk (rs2456449: OR=1.37; 95%CI 1.12-1.68; p=0.0022). In addition, IMMEnSE cases and controls were also genotyped for three MM risk SNPs from the first genome-wide association study (GWAS), and the association of two of them (rs4487645 on chromosome 7p15.3 and rs6746082 on chromosome 2p23.3) was confirmed. Finally, SNPs of key telomere-related genes were genotyped and telomere length was measured in MM cases and controls, and a pleiotropic and functional variant of the TERT gene was found to be associated with reduced MM risk (rs2242652: OR=0.81; 95%CI 0.72-0.92; p=0.001). A suggestive association between longer telomeres and increased MM risk was also found (ptrend=0.01).

We will study new SNPs emerging as promising candidates from ongoing GWAS on MM risk and survival, as well as SNPs of key genes involved in the pathogenesis of MM. Finally, we plan to study methylation status of key genes involved in MM etiology, and mitochondrial copy number. The role of all these factors will be investigated in relation to MM risk and prognosis.

Collection of samples and data of MM cases and controls is ongoing, as well as of subjects with monoclonal gammopathy of undetermined significance (MGUS).

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Centers involved in IMMEnSE

Figure 1

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Centers involved in IMMEnSE

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