Myelodysplastic Syndromes (MDS)

Demographic and Genetic Risk Factors

The median age at diagnosis of MDS is approximately 70 years, with MDS predominantly affecting the elderly 1, 2
The incidence of MDS is approximately 4 cases/100,000 inhabitants/year, increasing to 40-50/100,000 in patients aged ≥70 years 1, 2
In Asian populations, MDS tends to occur at earlier ages, presents more often with hypocellular marrow, and has a lower incidence of 5q deletion syndrome but higher frequency of trisomy 8 1, 2
Associated genetic conditions include Down syndrome, Fanconi anemia, and Neurofibromatosis, which are associated with an increased risk of MDS 1, 2
Germline mutations identified in familial cases include DDX41, GATA2, RUNX1, ANKRD26, ETV6, and Telomerase complex genes (TERC, TERT) 1, 2
Inherited predisposition is seen in one-third of pediatric MDS cases and should be assessed in young adults with MDS and families with multiple cases of MDS, AML, or aplastic anemia 1, 2

Agricultural and industrial work are associated with a higher incidence of MDS 1, 2
Exposure to chemotherapy agents, such as alkylating agents and purine analogues, increases the risk of developing MDS 1, 2
Radiotherapy or ionizing radiation also increases the risk of MDS 1, 2
Benzene and its derivatives can increase the risk of developing MDS 1, 2
Tobacco smoking is a known risk factor for developing MDS 1, 2

Secondary MDS, particularly therapy-related MDS, typically presents with poor prognostic factors and complex cytogenetic abnormalities, often involving chromosomes 5, 7, and 17p (17p deletion) 1, 2
MDS develops through a multistep process involving cytogenetic changes and/or gene mutations, abnormalities of the bone marrow microenvironment, and widespread gene hypermethylation at advanced stages 1, 2
The etiology of MDS is known in only about 15% of cases, with most cases being idiopathic, while known causes include genetic predisposition, exposure to chemotherapy agents, radiation, environmental toxins, and lifestyle factors such as tobacco smoking 1, 2