1423PInferring the correlation between incidence rates of melanoma and the average tumour-specific epitope binding ability of HLA class I molecules in different populations

Abstract Background Human Leucocyte Antigen (HLA) molecules are encoded by the most polymorphic genes in the human genome. The genetic variation of these genes are considerable across different geographic subpopulations. We hypothesised that this genetic variation might contribute to the risk of melanoma both at population and subject level. Methods We developed a cancer risk predictor based on the complete HLA class I genotype of individuals. The HLA-score, used in the predictor describes the ability of the HLA class I alleles of an individual to bind epitopes derived from 48 selected tumor antigens as an indicator of the breadth of the tumor-specific T-cell responses. We collected HLA data for subjects from 20 different geographic regions (ethnic populations) (n = 3278) as well as the corresponding melanoma incidence rates. The average HLA-scores were compared to the incidence rates. We also classified a mixed US population consisting of melanoma and healthy subjects based on their HLA-score. Results On population level, we found significant correlation between the incidence rates of melanoma and average HLA-scores in different geographic regions (R2 = 0.5005; p