Bone marrow cancer refers to malignancies originating in the spongy tissue inside bones, where blood cells are produced. This marrow contains stem cells that develop into red blood cells, white blood cells, and platelets. When these cells grow abnormally or too rapidly, bone marrow cancer can develop, disrupting normal blood cell production and function. This article explores the genetic aspects of these cancers and their potential for inheritance.
Understanding Heredity in Cancer
Cancer development often involves changes in a person’s genes. Genetic changes can be categorized into two main types: inherited (germline) and acquired (somatic). Inherited mutations are passed down from a parent to a child, present in every cell from birth. These germline mutations can significantly increase an individual’s risk of developing certain cancers, leading to hereditary cancer.
In contrast, acquired mutations occur during a person’s lifetime. These mutations can result from environmental exposures, errors during cell division, or the aging process. Acquired mutations are present only in the affected cells and cannot be passed on to offspring. The vast majority of cancers, including many bone marrow cancers, arise from these acquired genetic changes and are considered sporadic, rather than hereditary.
Genetic Links in Bone Marrow Cancers
The hereditary component of bone marrow cancers varies significantly, though a strong inherited link is generally uncommon. Multiple myeloma, a cancer of plasma cells, is not typically hereditary, as its development usually involves acquired mutations. However, a family history of multiple myeloma can elevate an individual’s risk by up to four times compared to the general population. Conditions like monoclonal gammopathy of undetermined significance (MGUS), a precursor to multiple myeloma, show increased prevalence in first-degree relatives, suggesting an inherited predisposition. Recent research indicates that inherited differences in BRCA1 and BRCA2 genes, known for their role in other cancers, are associated with an increased risk of multiple myeloma.
Leukemias, cancers of white blood cells, are generally not hereditary, though they involve underlying DNA mutations. Most cases stem from acquired genetic changes. However, certain rare genetic syndromes and gene mutations can increase the risk of developing leukemia. For example, mutations in the RUNX1 gene can increase the risk of acute myeloid leukemia (AML) and familial platelet disorder. Other genes like GATA2 and CEBPA are associated with familial forms of AML and myelodysplastic syndrome (MDS), leading to a higher lifetime risk. Congenital syndromes such as Down syndrome, Fanconi anemia, and Li-Fraumeni syndrome increase the likelihood of developing certain leukemias.
Myelodysplastic syndromes (MDS) are a group of disorders where the bone marrow does not produce enough healthy blood cells. While MDS is predominantly a sporadic disease affecting older individuals, rare familial forms exist. These familial MDS syndromes are linked to germline mutations in genes such as RUNX1, GATA2, and DDX41. Individuals with these inherited mutations may develop MDS younger than those with sporadic forms.
Lymphomas, cancers originating in the lymphatic system that can involve bone marrow, are not considered directly inherited. A family history of lymphoma slightly increases an individual’s risk. First-degree relatives of individuals with non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), or chronic lymphocytic leukemia (CLL) have an elevated risk, with studies showing a 1.7-fold to 8.5-fold increased risk depending on the lymphoma subtype. This increased risk is due to shared genetic variants or a combination of small inherited genetic changes.
Family Risk Assessment and Genetic Counseling
For individuals concerned about a hereditary risk of bone marrow cancer, family risk assessment and genetic counseling offer valuable guidance. Genetic counseling is generally recommended with a strong family history of bone marrow cancers, especially if diagnoses occurred at a younger age or if multiple family members are affected. This process involves a detailed review of an individual’s personal and family medical history, often extending to multiple generations, to identify patterns suggesting an inherited predisposition.
A genetic counselor assesses the likelihood of an inherited cancer syndrome and discusses implications for the individual and their family. They explain the benefits and limitations of genetic testing, which involves analyzing DNA for inherited mutations that increase cancer risk. Identifying such a mutation provides important information for managing health, including early screening or preventive measures. Even with a family history, the overall risk may be low, and professional guidance clarifies individual circumstances and informs decisions about health management.