Distinct Cancer Risk Profiles in Patients With Systemic Sclerosis With Autoantibody Stratification

Patients with systemic sclerosis (SSc) face increased cancer risk compared to the general population, yet current evidence on specific cancer patterns and their relationship to autoantibody status remain poorly characterized. This study seeks to evaluate cancer risk patterns in patients with SSc and investigate associations between specific autoantibodies and cancer development.

This multicenter cohort study analyzed five-year cancer incidences in 66,637 adults with SSc versus matched controls with seborrheic keratosis using electronic medical records from 128 health care organizations (from 2014 to 2024). Patients were stratified by autoantibody status (RNA polymerase III, anticentromere, or anti-Scl-70) when available. Primary outcomes included five-year incidences of hematologic and solid-organ cancers, with hazard ratios (HRs) calculated via Cox proportional hazards regression.

Patients with SSc demonstrated elevated five-year all-type cancer risk (HR 1.17, 95% confidence interval [CI] 1.11-1.23). Hematologic cancer risk was significantly increased (HR 1.68, 95% CI 1.50-1.88), particularly for multiple myeloma (HR 2.13, 95% CI 1.61-2.81) and myelodysplastic syndromes (HR 2.03, 95% CI 1.49-2.77). For solid-organ cancers (HR 1.23, 95% CI 1.16-1.31), esophageal cancer showed the highest risk (HR 3.96, 95% CI 2.36-6.65), followed by lung cancer (HR 2.32, 95% CI 2.00-2.69). Among autoantibody subgroups, patients with anti-Scl-70 positivity showed increased overall cancer risk (HR 1.40, 95% CI 1.03-1.92) and patients with RNA polymerase III positivity had higher rates of hematologic cancers (HR 2.20, 95% CI 1.10-4.28), whereas patients with anticentromere positivity demonstrated no increased cancer risks.

Patients with SSc demonstrate significantly increased risks for both hematologic and solid-organ cancers, with risk profiles varying by autoantibody status. These findings suggest the need for targeted cancer screening strategies in SSc and further research to confirm the generalizability of these findings.