Epidemiology and etiopathogenesis of multiple myeloma and monoclonal gammapathy of undetermined significance

Abstract

Multiple myeloma (MM) accounts for about 13% of haematological malignancies. Etiopatho-genesis is still not fully understood. Confirmed risk factors include the following: age, male sex, black race and MM among first-degree relatives. MM may be preceded by monoclonal gammapathy of undetermined significance (MGUS). The risk of progression is about 1% per year. Genetic changes, proinflammatory and proangiogenic cytokines and some infections may play a role in this risk. With regard to lifestyle risk factors, only obesity and overweight were associated with increased MM incidence and elevated risk for transformation of MGUS to MM. Regarding occupational exposure, there is an increased risk of MM among farmers, firefighters and hairdressers. As far as autoimmune diseases are concerned, only ankylosing spondylitis and pernicious anemia are associated with significantly increased MM risk. Increased risk of MM was also reported in relatives of MM patients, especially in first-degree relatives and in African-American families. The risk of MGUS is elevated in both first-degree relatives of MM and MGUS patients. Data from genetic analysis indicated translocations involving immunoglobulin heavy chain (IGH) loci, hyperphosphorylation of several proteins which are the targets for paraproteins produced by malignant plasma cells and single nucleotide polymorphisms (susceptibility loci) as the potential genetic predisposition to multiple myeloma. The mechanism of heterogeneity of clinical manifestations of MM is not known. Anemia is less frequent in patients whose relatives were diagnosed with hematologic malignancy compared to those with a negative family history. In patients from a younger age group, osteolytic bone lesions were more common than in older patients. In conclusion, environmental exposures modify the genetic predisposition to MM and MGUS.