Association between anti-synthetase syndrome and malignancy: a systematic review and meta-analysis.

[OBJECTIVES] Anti-synthetase syndrome (ASyS) is a rare autoimmune disorder defined by anti-synthetase antibodies. While malignancy is established in DM, its association with ASyS remains unclear. We aimed to estimate malignancy prevalence in ASyS and assess whether autoantibody subtype, age, sex or clinical features influence malignancy risk.

[METHODS] We performed a systematic review and meta-analysis following PRISMA guidelines and a PROSPERO protocol (CRD42024540200). PubMed, Embase, Web of Science Core Collection, Scopus and CENTRAL were searched for studies reporting malignancy in adult ASyS patients. A random intercept logistic regression model estimated pooled prevalence and enabled meta-regression. Risk of bias was assessed with a modified Newcastle-Ottawa Scale, and certainty of evidence with GRADE.

[RESULTS] Forty-three studies including 4451 patients were eligible. The pooled malignancy prevalence was 8.3% (95% CI 7.5-9.1%; I2 = 70%). Older age (P = 0.018) and longer follow-up (P = 0.013) were significantly associated with malignancy. No significant associations were found with anti-Jo-1 positivity or other clinical manifestations of ASyS. Malignancy prevalence numerically varied across antibody subtypes (6.4% anti-Jo-1 to 13.3% anti-OJ). Breast, lung and colon cancer were frequently reported.

[CONCLUSION] The overall malignancy risk in ASyS appears low. Age and length of follow-up were associated with higher malignancy risk, whereas clinical manifestations were not. Although the malignancy rates differed between antibody subtypes, with the numerically highest prevalence in anti-OJ antibodies, these findings were not statistically significant. Since the risk of malignancy in the ASyS population appears to be low in general, cancer screening should be tailored according to the patients age and sex.