Does a Multiple Myeloma Polygenic Risk Score Predict Overall Survival of Patients with Myeloma?
Research output: Contribution to journal › Journal article › Research › peer-review
Background: Genome-wide association studies (GWAS) of multiple myeloma in populations of European ancestry (EA) identified and confirmed 24 susceptibility loci. For other cancers (e.g., colorectum and melanoma), risk loci have also been associated with patient survival. Methods: We explored the possible association of all the known risk variants and their polygenic risk score (PRS) with multiple myeloma overall survival (OS) in multiple populations of EA [the International Multiple Myeloma rESEarch (IMMEnSE) consortium, the International Lymphoma Epidemiology consortium, CoMMpass, and the German GWAS] for a total of 3,748 multiple myeloma cases. Cox proportional hazards regression was used to assess the association between each risk SNP with OS under the allelic and codominant models of inheritance. All analyses were adjusted for age, sex, country of origin (for IMMEnSE) or principal components (for the others) and disease stage (ISS). SNP associations were meta-analyzed. Results: SNP associations were meta-analyzed. From the meta-analysis, two multiple myeloma risk SNPs were associated with OS (P < 0.05), specifically POT1-AS1-rs2170352 [HR = 1.37; 95% confidence interval (CI) = 1.09-1.73; P = 0.007] and TNFRSF13B-rs4273077 (HR = 1.19; 95% CI = 1.01-1.41; P = 0.04). The association between the combined 24 SNP MM-PRS and OS, however, was not significant. Conclusions: Overall, our results did not support an association between the majority of multiple myeloma risk SNPs and OS. Impact: This is the first study to investigate the association between multiple myeloma PRS and OS in multiple myeloma.
| Original language | English |
|---|---|
| Journal | Cancer Epidemiology Biomarkers and Prevention |
| Volume | 31 |
| Issue number | 9 |
| Pages (from-to) | 1863-1866 |
| ISSN | 1055-9965 |
| DOIs | |
| Publication status | Published - 2022 |
Bibliographical note
Funding Information:
of the study. J.M. Zaucha reports non-financial support from Roche; personal fees from Abbvie, Takeda, Jansssen; grants from BMS outside the submitted work. H. Goldschmidt reports grants, personal fees, and other support from Amgen, BMS, Celgene, Chugai, Janssen, Sanofi; other support from Incyte, Molecular Partners, MSD, Mundipharma GmbH, Takeda, Adaptive Biotechnology; personal fees and other support from Novartis; and personal fees from GSK outside the submitted work. E. Iskierka-Jazdzewska reports personal fees and non-financial support from Sandoz, Roche, Novartis, and Janssen; personal fees from AstraZeneca, Celgene outside the submitted work. C.M. Vachon reports other support from Mayo Clinic Cancer Center and grants from NCI during the conduct of the study. No disclosures were reported by the other authors.
Funding Information:
R.Z. Orlowski reports grants from Asylia Therapeutics, Inc., BioTheryX, Inc., and Heidelberg Pharma; other support from CARsgen Therapeutics, Celgene, Exelixis, Janssen Biotech, Sanofi-Aventis, and Takeda Pharmaceuticals North America, Inc.; and personal fees from Abbvie, Amgen, Inc., BioTheryX, Inc., Bristol-Myers Squib, Celgene, EcoR1 Capital LLC, Forma Therapeutics, Genzyme, GSK Biologicals, Janssen Biotech, Karyopharm Therapeutics, Inc., Meridian Therapeutics, Monte Rosa Therapeutics, Neoleukin Corporation, Oncopeptides AB, Regeneron Pharmaceuticals, Inc., Sanofi-Aventis, and Takeda Pharmaceuticals North America, Inc. outside the submitted work; and R.Z. Orlowski is a founder of Asylia Therapeutics, Inc., with associated patents and an equity interest, though this technology does not bear on the current article. S.K. Kumar reports grants from NCI during the conduct of the study; and research funding for clinical trials to the institution: Abbvie, Amgen, Allogene, AstraZeneca, BMS, Carsgen, GSK, Janssen, Novartis, Roche-Genentech, Takeda, Regeneron, Molecular Templates; reports consulting/advisory board participation: (with no personal payments) Abbvie, Amgen, BMS, Janssen, Roche-Gen-entech, Takeda, AstraZeneca, Bluebird Bio, Epizyme, Secura Biotherapeutics, Mon-terosa therapeutics, Trillium, Loxo Oncology, K36, Sanofi, ArcellX, and (with personal payment) Oncopeptides, Beigene, Antengene, GLH Pharma. E. Ziv reports grants from The UCSF Stephen & Nancy Grand Multiple Myeloma Translational Initiative and grants from NIH/NCI during the conduct of the study. G.G. Giles reports grants from National Health and Medical Research Council (Australia) during the conduct of the study. R.L. Milne reports grants from NHMRC during the conduct
ID: 326738106