From the Guidelines
Multiple myeloma is generally not considered a genetically inherited disease, but there can be a familial component in some cases, particularly in African American individuals, where having a family history of multiple myeloma or a related plasma cell dyscrasia is a strong risk factor for developing the disease, with first-degree relatives having a 2–3 times higher risk of developing the disease 1. While multiple myeloma itself is not typically passed down directly from parent to child, having a first-degree relative (parent, sibling, or child) with multiple myeloma does slightly increase an individual's risk of developing the disease. However, this increased risk is relatively small. The vast majority of multiple myeloma cases occur sporadically, meaning they develop due to acquired genetic mutations over a person's lifetime rather than inherited genetic factors. These mutations typically occur in plasma cells, a type of white blood cell, and are not present in other cells of the body. Some key points to consider include:
- Having a family history of multiple myeloma may increase an individual's risk of developing the disease, particularly in African American individuals, with an odds ratio of 5.52,95% CI: 1.87–16.27 1.
- Genetic inheritance may play a role in increased incidence of multiple myeloma and its precursor condition in African American population, with a higher prevalence of autosomal dominantly inherited hyperphosphorylated form of the paratarg-7 protein (pP-7) carriers among patients with multiple myeloma of African American descent compared to other ethnic groups 1.
- A meta-analysis of genome wide association studies (GWAS) has identified loci in African American populations potentially associated with multiple myeloma that are distinct from the risk alleles identified in European American populations 1. It's essential to note that even in families with multiple cases of multiple myeloma, the disease is not considered strictly hereditary. Environmental factors, aging, and random genetic changes likely play more significant roles in its development. If you have a family history of multiple myeloma, it's advisable to discuss this with your healthcare provider. They may recommend more frequent check-ups or screenings, but there are currently no specific preventive measures for individuals with a family history of the disease.
From the Research
Genetic Inheritance of Multiple Myeloma
- Multiple myeloma (MM) has been found to have a significant hereditary component, with emerging evidence suggesting a genetic link to the disease 2.
- Studies have shown that individuals with a family history of hematologic malignancies are at increased risk of developing MM, with the risk being higher for those with a family history of MM itself 3.
- Genome-wide association studies (GWAS) have identified common genetic variants linked to MM, as well as rare, high-penetrance variants in key susceptibility genes 2, 4.
- Pathogenic germline variants (PGVs) in DNA repair genes, such as BRCA1 and BRCA2, have been found to be significantly enriched in patients with MM, suggesting a possible genetic predisposition to the disease 5.
- The presence of PGVs in DNA repair genes has been associated with younger age at diagnosis, personal or familial cancer history, and longer progression-free survival after treatment 5.
Key Findings
- A family history of MM is a significant risk factor for the disease, with a higher risk observed in individuals with a strong family history of cancer 3.
- Genetic variants in DNA repair genes, such as BRCA1 and BRCA2, are associated with an increased risk of MM 5.
- The presence of PGVs in DNA repair genes may have implications for treatment and outcomes, with high-penetrance PGV carriers potentially benefiting from high-dose melphalan and autologous stem-cell transplantation 5.
Implications for Genetic Testing
- Genetic testing may be considered for young or newly diagnosed patients with a personal or family cancer history, given the potential for unsuspected cancer predisposition syndromes 5.
- Routine germline screening may be advocated for high-risk MM populations, particularly those with a strong family history of cancer or early-onset disease 2.