Dissecting the Genetic Architecture of Tanning and Sunburn as Skin Cancer Risk Factors

UVR is the main modifiable risk factor for skin cancer, causing direct DNA damage. Genetic factors influence UV-mediated skin cancer risk by modulating the skin's response to UVR, typically seen as acute inflammation (sunburn) or a delayed increase of melanin production (tanning). Although biologically distinct, most studies to date have not differentiated between these outcomes, conflating their genetic risk profiles. The purpose of this study was to compare the genetics of tanning and sunburn. We analyzed genetic data from 24,163 participants in the QSkin cohort, which separately measured tanning and sunburn propensity. GWAS was performed to identify the associated loci and estimate heritability and genetic correlation. A multitrait analysis was conducted to enhance discovery power, incorporating published GWAS from UK Biobank. Sixteen genomic risk loci were identified for tanning and sunburn; 8 loci were overlapped. Heritability was 37% for tanning and 28% for sunburn. The genetic correlation coefficient was -0.92 (95% confidence interval = -0.99 to -0.85). Multitrait analysis identified 108 risk loci, of which 63 were shared. Most genetic variants affected both traits, suggesting a similar underlying biological pathway. Overall, our analysis found no evidence to suggest that the genetic structure of tanning differs substantively from that of sunburn.