Issues

The cover image is adapted from Figure 1 in the article, “Gene-Environment Analyses in a UK Biobank Skin Cancer Cohort Identifies Important SNPs in DNA Repair Genes That May Help Prognosticate Disease Risk,” by Jeremian and colleagues. Despite well-established relationships between sun exposure and skin cancer pathogenesis/progression, specific gene-environment interactions in at-risk individuals remain poorly understood. Given the demonstrated limitations of using genetic data in isolation and the projected exponential increase in availability of diverse patient data, it is important to explore whether SNP analysis alone is sufficient for quantifying disease risk, and whether such analysis should be combined with demographic, behavioral, and clinical information especially in dermatology. As this technology is used by millions of patients, oncologists and dermatologists need to understand and lead the effort of using genome-wide association studies appropriately to identify valuable predictive genetic variants in the context of clinical information. To investigate these relationships in greater depth, the authors leveraged a dataset of four skin cancers and matched healthy controls from the UK Biobank database and performed associations between disease status, demographic and behavioral factors related to the impact of UV exposure, and SNP genotypes across selected 190 DNA repair genes. Figure 1 shows the impact of demographic, environmental and behavioral variables on keratinocyte and melanoma skin cancer risk determined using multinomial logistic regression. The authors identified novel risk factors for keratinocyte carcinomas and melanoma, highlighted the prognostic value of several FANCA alleles among individuals with a history of sunlamp use and childhood sunburns, and demonstrated the importance of combining genetic and clinical data in disease risk stratification. This study revealed genome-wide associations with important implications for understanding skin cancer risk in the context of the rapidly evolving field of precision medicine. For more information, see the article beginning on page 1599.