Anti-RNA Pol III Cancer Association — SCE Rheumatology MCQ

Correct answer: B — It identifies a subgroup in which cancer clusters around systemic sclerosis onset, consistent with a possible cancer-triggered autoimmune response.

Explanation lettering: E = shown as A · D = shown as C · A = shown as D · C = shown as E

Anti-RNA polymerase III-positive systemic sclerosis has a particularly strong temporal association with malignancy around disease onset, commonly operationalised as within approximately 3 years. Breast cancer is a well-described example, but the association is not confined to one tumour type. Tumour POLR3A alterations may generate cellular and humoral responses that cross-react with native RNA polymerase III, providing a plausible cancer-triggered autoimmune model. This is a temporal cancer-associated phenotype rather than simply a uniform lifelong risk (A). It can precede immunosuppressive treatment, excluding treatment-induced malignancy as the explanation (C), and is not restricted to lung cancer or interstitial lung disease (D). Cohort analyses show that the short cancer–systemic sclerosis interval remains associated with anti-RNA polymerase III positivity after adjustment for relevant covariates, making E incorrect.

Reference: Moinzadeh P, Fonseca C, Hellmich M, et al. Association of anti-RNA polymerase III autoantibodies and cancer in scleroderma. Arthritis Research & Therapy. 2014;16:R53. https://pubmed.ncbi.nlm.nih.gov/24524733/