Genetic Influences in Cancer‐Associated Myositis

Abstract

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.

Proximal Muscle Weakness in a Collegiate Volleyball Athlete

“…Classically, those with juvenile dermatomyositis tend to have more vasculopathy, calcinosis, and ulceration but overall better prognosis. In adults, there is a high risk of malignancies, interstitial lung disease, and amyopathic disease (7,8).…”

Familial Co‐Aggregation of Idiopathic Inflammatory Myopathies and Cancer: A Swedish Population‐Based Study

“…HLA-B*08:01 confers risk of DM and also for lung cancer (15,39). A recent review on genetic influences in cancer-associated myositis addressed similar oncogene expression profiles between DM and several hematologic and solid malignancies (40). Smoking has been suggested as a risk factor of IIM, acute myeloid leukemia, lung cancer, and liver cancer (5,7).…”

Clinical features and risk factors of lung cancer in elderly patients with dermatomyositis

“…Dermatomyositis (DM), an uncommon chronic autoimmune disease, is a kind of idiopathic inflammatory myopathy (IIM) characterized by muscle pain and weakness, unique skin findings, such as heliotrope rash, or gottron's papules, or gottron's sign, or V‐sign or shawl sign, etc 1 . In recent years, a relationship between DM and malignancy has been well established 2,3 . Immune dysfunction, chronic inflammation, older age and immunosuppressive therapy for DM have been linked to an increased incidence of malignancy 4 .…”

“… 1 In recent years, a relationship between DM and malignancy has been well established. 2 , 3 Immune dysfunction, chronic inflammation, older age and immunosuppressive therapy for DM have been linked to an increased incidence of malignancy. 4 It has been reported that malignancies are detected in approximately 10%–47% of DM patients and associated with high mortality.…”