Association of alport syndrome with NMSC: A retrospective case-control study using the trinetx dataset

Summary: Abstract Body: Alport syndrome (AS) is a genetic condition, with predominantly X-linked dominance and autosomal variants in inheritance. It affects up to 60,000 people in the US. It is a disorder with mutations in COL4A3, COL4A4 and COL4A5 that affect type IV collagen, resulting in chronic kidney inflammation, ocular abnormalities, and sensorineural hearing loss. Patients are managed for chronic kidney disease and may undergo kidney transplantation. Systemic inflammation is a key characteristic of the syndrome, yet, to date AS has been associated with diffuse leiomyomatosis and not been investigated for associations with other neoplasms. Given its impact on skin integrity, this study sought to look at the association between AS and non-melanoma skin cancer (NMSC). The TriNetX (Cambridge, MA) US network was utilized to conduct a retrospective case-control study. The case group was defined using the ICD-10 code for individuals diagnosed with AS. The controls included patients who had undergone at least one general outpatient annual physical examination and had no documented history of AS, as identified using ICD-10 codes. We performed adjusted analyses with 1:1 propensity score matching between cohorts for age at index, sex, black and white race and ethnicity. Of 114,251,452 individuals in the US network, 41,939 met AS diagnosis criteria. 37,905 were included after matching to controls. Individuals with AS were more likely to have a diagnosis of SCC and BCC compared to those without (SCC: OR: 4.152, 95% CI: 2.577,6.687, p<0.0001) (BCC: OR: 3.942, 95% CI: 2.954,5.262, p<0.0001). Our results suggest that there is a significantly increased risk of NMSC in patients with AS. No case-control studies have been conducted on this association, making this the largest retrospective study available. It is possible that factors such as chronic inflammation, immunosuppression following transplant and defects in the skin barrier from collagen IV mutation could potentially explain our findings. Further investigation into this association and its underlying mechanism is warranted. Ruhi Kanwar^{1, 2}, Vinod Nambudiri² 1. Harvard Medical School, Boston, MA, United States. 2. Dermatology, Brigham and Women's Hospital, Boston, MA, United States. UV Biology/Injury and Non-melanoma Cancers