Updated insights into cancer risk and pathogenesis in systemic lupus erythematosus; a nephrology viewpoint on recent evidence

Abstract

Patients with systemic lupus erythematosus (SLE) exhibit a distinct cancer risk profile characterized by increased susceptibility to hematologic malignancies such as non-Hodgkin lymphoma (NHL), as well as certain solid tumors like lung, thyroid, and hepatobiliary cancers. Conversely, they also demonstrate a reduced risk for some cancers including breast, melanoma, and prostate cancer. This unique pattern is influenced by a combination of disease-related immune dysregulation and treatment-related factors. Additionally, immunosuppressive therapy administered in SLE management, including agents like cyclophosphamide, is known to contribute to an elevated risk of malignancies such as cervical dysplasia and certain hematologic cancers. However, specific immunosuppressants like calcineurin inhibitors have shown no significant increase in cancer incidence in some cohorts, suggesting that cancer risk is multifactorial and may depend on the type and duration of immunosuppression. However, in SLE patients, screening practices for cancers like cervical cancer are suboptimal despite their increased risk. However, some studies have found lower cervical cancer screening rates in women with SLE compared to control subjects, which influenced by factors like age, income, and comorbidities. Improved screening uptake is crucial for early cancer detection and better outcomes in this vulnerable population. Moreover, lupus nephritis enhances cancer risk and progression through complex interplay of chronic inflammation, immune dysregulation, treatment effects, and molecular pathway alterations. Inflammation-induced oxidative stress and impaired autophagy, combined with immunosuppressive therapies, provide a background for malignant transformation and decreased tumor immune surveillance.

Keywords: Lupus nephritis, Cancer risk, Oxidative stress, Systemic lupus erythematosus, Inflammation