Association between Human Leukocyte Antigen Type and Keratinocyte Carcinoma Risk in Renal Transplant Recipients

Keratinocyte carcinoma (KC), defined as squamous cell carcinoma and basal cell carcinoma, is the most common malignancy among white, non-Hispanic renal transplant recipients. Although recent genome-wide association studies reported that class II HLA is associated with KC risk, epidemiologic data on HLA type and KC risk in renal transplant recipients is limited. Using an institutional cohort of white, non-Hispanic renal transplant recipients transplanted between 1993 and 2017, we examined the association between pretransplant molecular HLA types and KC risk. Posttransplant KCs were captured using the International Classification of Diseases codes and validated using pathology reports. Cox proportional hazards regression models were used to estimate hazard ratios of incident KC, squamous cell carcinoma, and basal cell carcinoma, adjusting for age, male sex, history of KC, Charlson comorbidity index, HLA mismatch, transplant type, year of transplant, and the type of immunosuppression. Among 617 subjects (mean age 53 years, 67% male), 10% developed posttransplant KC. Multivariable Cox regression analyses showed HLA-DRB1∗13 was associated with KC risk (hazard ratio, 1.84; 95% confidence interval, 1.00–3.38) and squamous cell carcinoma risk (hazard ratio, 2.24; 95% confidence interval, 1.12–4.49), whereas HLA-DRB1∗14 (hazard ratio, 2.81; 95% confidence interval, 1.14–6.91) was associated with basal cell carcinoma risk. Our findings suggest that a subset of renal transplant recipients with specific HLA polymorphisms may be at increased KC risk.