A groundbreaking study has identified a potential genetic risk factor for multiple myeloma, revealing that pathogenic germline variants (PGVs) in hereditary cancer genes may contribute to the disease. The study analysed the genetic makeup of nearly 1,700 multiple myeloma patients, uncovering that up to 10% may have undiagnosed cancer predisposition syndromes.
Researchers from two independent cohorts examined germline exomes from 895 and 786 multiple myeloma patients. They found PGVs in 8.6% of the Discovery cohort and 11.5% of the Replication cohort, with a notable prevalence of PGVs in DNA repair genes. Most significantly, they discovered that variants in the BRCA1 and BRCA2 genes, typically associated with breast and ovarian cancers, were enriched in multiple myeloma patients compared to healthy controls. Notably, patients carrying BRCA2 PGVs had a higher risk for the disease, with five out of eight showing a somatic loss of heterozygosity in the gene.
The study also highlighted that PGVs linked to autosomal dominant cancer predispositions were associated with earlier diagnosis, a family history of cancer, and longer progression-free survival following high-dose melphalan and autologous stem-cell transplantation. Researchers are calling for genetic testing in younger patients or those with a personal or family history of cancer, as early identification of these high-risk variants could lead to more personalized and effective treatment options.
This research underscores the importance of genetic screening in multiple myeloma and could significantly impact clinical practices for diagnosis and treatment.
Reference
Thibaud S et al. Multiple Myeloma Risk and Outcomes Are Associated with Pathogenic Germline Variants in DNA Repair Genes. Blood Cancer Discovery. 2024;5(6):428-41.
