A major international study has found that patients with systemic sclerosis (SSc) face a significantly higher risk of developing cancer than the general population, with the pattern and magnitude of risk varying according to specific immune markers.
Elevated Cancer Risk in Autoimmune Disease
Researchers analyzed medical data from more than 66,000 adults diagnosed with systemic sclerosis between 2014 and 2024, comparing their outcomes against a matched control group of patients with benign skin growths known as seborrheic keratoses. The multi‑center cohort study, which drew on electronic medical records from 128 healthcare organizations worldwide, provides one of the most comprehensive assessments to date of malignancy patterns in this rare autoimmune disease.
Distinct Patterns Linked to Autoantibody Type
Over a five‑year period, the study found that individuals with systemic sclerosis had a 17 percent higher overall risk of developing cancer. The association was strongest for blood cancers, where risk rose by nearly 70 percent. In particular, cases of multiple myeloma and myelodysplastic syndromes were more than twice as common among those with SSc as in matched controls.
Solid organ cancers were also more frequent, with an average hazard ratio of 1.23. Esophageal cancer showed the strongest link—nearly four times the risk seen in the control group—followed by lung cancer, which was more than twice as likely among patients with systemic sclerosis.
Importantly, the study found that cancer risk was not uniform across all patients but varied depending on the type of autoantibodies present. Among those who tested positive for the anti‑Scl‑70 antibody, the overall cancer risk rose by 40 percent. Meanwhile, patients with antibodies to RNA polymerase III were more likely to develop hematologic cancers, with risk more than doubling compared to controls. By contrast, no significant elevation in cancer risk was observed among patients positive for anti‑centromere antibodies.
Call for Targeted Screening and Further Research
Researchers say the findings underscore the complex interplay between immune dysregulation and cancer susceptibility in systemic sclerosis. They suggest that clinicians consider tailoring cancer screening strategies according to antibody profiles, to identify high‑risk patients earlier and improve outcomes.
Reference
Mahajan A et al. Distinct cancer risk profiles in patients with systemic sclerosis with autoantibody stratification.
