Genetic Influences in Cancer-Associated Myositis

Arthritis Rheumatol. 2023 Feb;75(2):153-163. doi: 10.1002/art.42345. Epub 2022 Dec 20.


Idiopathic inflammatory myopathies (IIMs) comprise a heterogeneous group of rare immune-mediated disorders that primarily affect muscles but also lead to dysfunction in other organs. Five different clinical subphenotypes of IIM have been distinguished: dermatomyositis, polymyositis, inclusion body myositis, antisynthetase syndrome, and immune-mediated necrotizing myopathy. Excess mortality and morbidity associated with IIM are largely attributed to comorbidities, particularly cancer. The risk of malignancy is not equally distributed among IIM groups and is particularly high among patients with dermatomyositis. The cancer risk peaks around 3 years on either side of the IIM diagnosis and remains elevated even 10 years after the onset of the disease. Lung, colorectal, and ovarian neoplasms typically arise before the onset of IIM, whereas melanoma, cervical, oropharyngeal, and nonmelanoma skin cancers usually develop after IIM diagnosis. Given the close temporal proximity between IIM diagnosis and the emergence of malignancy, it has been proposed that IIM could be a consequence rather than a cause of cancer, a process known as a paramalignant phenomenon. Thus, a separate group of IIMs related to paramalignant phenomenon has been distinguished, known as cancer-associated myositis (CAM). Although the relationship between IIM and cancer is widely recognized, the pathophysiology of CAM remains elusive. Given that genetic factors play a role in the development of IIM, dissection of the molecular mechanisms shared between IIM and cancer presents an opportunity to examine the role of autoimmunity in cancer development and progression. In this review, the evidence supporting the contribution of genetics to CAM will be discussed.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dermatomyositis* / complications
  • Dermatomyositis* / diagnosis
  • Dermatomyositis* / genetics
  • Humans
  • Melanoma* / genetics
  • Myositis*
  • Myositis, Inclusion Body* / diagnosis
  • Myositis, Inclusion Body* / pathology
  • Polymyositis*