Cancer Incidence and Risk Factors in PLA2R-Associated Membranous Nephropathy.

Abstract

To evaluate cancer incidence, cancer types, and effect of immunosuppressive therapy and clinical parameters on cancer diagnosis in patients with phospholipase A₂ receptor (PLA2R)-associated membranous nephropathy (MN). We conducted a retrospective cohort study of 239 adult patients with diagnosis of PLA2R-associated MN from January 1, 1996, to December 31, 2021. We assessed cancer incidence and explored the impact of immunosuppressive therapy, response to therapy, PLA2R antibody titers over time, and comorbidities in development of cancer. Cancer incidence in our cohort was higher than expected on the basis of an age-adjusted US general population with a standardized incidence ratio of 1.93. Age, smoking habits, and previous history of cancer significantly increased risk for development of cancer after diagnosis of MN. Cyclophosphamide was also associated with an increased incidence of cancer, although not statistically significant. Other types of immunosuppressive therapy, PLA2R titers over time, and remission status were not associated with an increase in risk of cancer. The increased incidence of cancer in our cohort seems to be independent of PLA2R titers, remission status, or renal function. These findings suggest that traditional cancer risk factors-such as age, smoking, and prior malignant disease-do not fully explain the elevated malignancy risk, suggesting that PLA2R itself may contribute to oncogenesis through mechanisms not yet understood.