Causal Assessment of Phenotypic Risk Factors with Keratinocyte Carcinoma

Previous observational and genomic-wide association studies (GWAS) suggested the association between several phenotypic factors and keratinocyte carcinoma, including lifestyle and dietary, photodamage-related conditions and socioeconomic status. The causal effect of these phenotypic factors in keratinocytes carcinoma etiology remains unclear. In this study, we utilized two-sample mendelian randomization analysis from multiple large-scale GWAS datasets of keratinocytes carcinoma including more than 300,000 patients. Genetic instrumental variables (IVs) were constructed by identifying single nucleotide polymorphisms (SNPs) that associate with corresponding factors. The inverse variance weighted (IVW) method and four robust MR approaches, including weighted median estimator, MR-Egger regression, simple mode and weighted mode were implemented for causal inferences and assess the sensitivity across findings. In this analysis, ease of skin tanning was identified as casual protective factor of keratinocyte carcinoma (Basal cell carcinoma: IVW OR = 0.718, 95% CI 0.654-0.788, p < 0.001; Cutaneous squamous cell carcinoma: IVW OR = 0.601, 95% CI 0.516-0.701, p < 0.001). Other phenotypic factors, such as coffee intake, alcohol consumption, smoking and socioeconomic status, indicated insignificant effects on keratinocyte carcinoma risk in the analysis, and therefore, our study does not support their roles in modifying keratinocytes carcinoma risks. Our extensive analysis provides strong evidence of the causative protective effect of ease of skin tanning in keratinocyte carcinoma. The findings suggest that individuals who are less prone to tanning may need to pay greater attention to sun protection in their daily activities to reduce the potential risk of keratinocyte cancers.

The online version contains supplementary material available at 10.1007/s43657-024-00174-w.