Recent advances in genetic research have significantly expanded our understanding of both cancers and skin diseases. Large-scale efforts like The Cancer Genome Atlas have mapped somatic mutations across various cancers, identifying key driver mutations and tumor suppressor genes critical for tumor initiation and progression. GWAS have also revealed numerous germline variants that increase cancer susceptibility. In dermatology, genetic studies have identified somatic driver mutations for melanoma and other skin cancers, while GWAS have uncovered susceptibility loci for chronic skin conditions like psoriasis.
However, most genetic studies have treated cancers and skin diseases as isolated conditions, potentially overlooking shared genetic underpinnings. Emerging evidence suggests that various cancers and skin diseases share genetic architecture and biological pathways, offering insight into common mechanisms of disease etiology. Understanding these shared genetic factors could enhance screening programs, support integrated preventive strategies, and inform treatments that address both disease types, ultimately streamlining drug development and repurposing efforts.
While cancer genetics has predominantly focused on somatic variants, germline variants-heritable mutations present in every cell-also play a critical role in disease susceptibility and impact the gene pool. Yet, their role across multiple cancers and skin diseases remains underexplored. Whole-genome sequencing (WGS) is essential for this work, as it offers a complete view of both coding and non-coding regions, covering rare and common variants missed in exome sequencing and imputed genotype arrays.
This project leverages WGS data from 500,000 UK Biobank participants to analyze the distinct and shared genetic landscapes of multiple cancers and skin diseases. By doing so, we aim to advance prediction, prevention, and treatment strategies for these interconnected diseases.
