Most cited article - PubMed ID 32433745
Search for multiple myeloma risk factors using Mendelian randomization
Multiple myeloma (MM) is a hematological malignancy caused by the clonal expansion of plasma cells. The incidence of MM worldwide is increasing with greater than 140 000 people being diagnosed with MM per year. Whereas 5-year survival after a diagnosis of MM has improved from 28% in 1975 to 56% in 2012, the disease remains essentially incurable. In this review, we summarize our current understanding of MM including its epidemiology, genetics and biology. We will also provide an overview of MM management that has led to improvements in survival, including recent changes to diagnosis and therapies. Areas of unmet need include the management of patients with high-risk MM, those with reduced performance status and those refractory to standard therapies. Ongoing research into the biology and early detection of MM as well as the development of novel therapies, such as immunotherapies, has the potential to influence MM practice in the future.
- Keywords
- clinical presentation, plasma cell disease, risks factors, survival, treatment,
- MeSH
- Cyclin D1 genetics MeSH
- Exosome Multienzyme Ribonuclease Complex genetics MeSH
- Genetic Predisposition to Disease MeSH
- Histone Demethylases genetics MeSH
- Immunotherapy methods MeSH
- Humans MeSH
- Survival Rate MeSH
- Multiple Myeloma diagnosis epidemiology genetics therapy MeSH
- Mutation MeSH
- Biomarkers, Tumor genetics MeSH
- Plasma Cells immunology pathology MeSH
- Repressor Proteins genetics MeSH
- Risk Factors MeSH
- Transcriptional Elongation Factors genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- CCND1 protein, human MeSH Browser
- CDCA7L protein, human MeSH Browser
- Cyclin D1 MeSH
- DIS3 protein, human MeSH Browser
- ELL2 protein, human MeSH Browser
- Exosome Multienzyme Ribonuclease Complex MeSH
- Histone Demethylases MeSH
- KDM1A protein, human MeSH Browser
- Biomarkers, Tumor MeSH
- Repressor Proteins MeSH
- Transcriptional Elongation Factors MeSH
In amyloid light chain (AL) amyloidosis, amyloid fibrils derived from immunoglobulin light chain are deposited in many organs, interfering with their function. The etiology of AL amyloidosis is poorly understood. Summary data from genome-wide association studies (GWASs) of multiple phenotypes can be exploited by Mendelian randomization (MR) methodology to search for factors influencing AL amyloidosis risk. We performed a 2-sample MR analyzing 72 phenotypes, proxied by 3461 genetic variants, and summary genetic data from a GWAS of 1129 AL amyloidosis cases and 7589 controls. Associations with a Bonferroni-defined significance level were observed for genetically predicted increased monocyte counts (P = 3.8 × 10-4) and the tumor necrosis factor receptor superfamily member 17 (TNFRSF17) gene (P = 3.4 × 10-5). Two other associations with the TNFRSF (members 6 and 19L) reached a nominal significance level. The association between genetically predicted decreased fibrinogen levels may be related to roles of fibrinogen other than blood clotting. be related to its nonhemostatic role. It is plausible that a causal relationship with monocyte concentration could be explained by selection of a light chain-producing clone during progression of monoclonal gammopathy of unknown significance toward AL amyloidosis. Because TNFRSF proteins have key functions in lymphocyte biology, it is entirely plausible that they offer a potential link to AL amyloidosis pathophysiology. Our study provides insight into AL amyloidosis etiology, suggesting high circulating levels of monocytes and TNFRSF proteins as risk factors.
