Genetic influences in cancer-associated myositis.

Idiopathic inflammatory myopathies comprise a heterogeneous group of rare immune-mediated disorders that primarily affect muscles, but also lead to dysfunction of other organs. Five different clinical sub-phenotypes of IIM have been distinguished: dermatomyositis, polymyositis, inclusion body myositis, anti-synthetase syndrome and immune-mediated necrotizing myopathy. Excess mortality and morbidity associated with IIM are by large 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 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 non-melanoma skin cancers usually develop after IIM diagnosis. Given the close temporal proximity between the start of IIM 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 IIM 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. Taken that genetic factors play a role in IIM development, dissection of molecular mechanisms shared between IIM and cancer gives 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.