638 Inverse genetic risk between cutaneous melanoma, basal cell carcinoma, squamous cell carcinoma and vitiligo

Several epidemiological studies have reported an inverse association between vitiligo and skin cancers such as cutaneous melanoma, basal cell carcinoma squamous carcinoma. There are conflicting reports whether this is a consequence of increased immunosurveillance observed in patients or rather shared genetic contribution. The latter hypothesis however, not currently sustained by available evidence. Herein, we compared 23 vitiligo-associated variants (P<5x10-8) from recently published genome-wide study identified three variants—contained within the TYR, MC1R-DEF8, RALY-EIF252-ASIP-ACHY-ITCH loci—that been associated with risk for carcinoma, concurrent decreased vitiligo. We then subjected GWAS summary statistics each cancer to unbiased two-sample mendelian randomization analysis. protective role development melanoma (effect size=-6.78x10-4; p=5.41x10-2), size=-1.29x10-3; p=1.77x10-3), size=-2.19-4; p=1.81x10-3). When signature was same analysis, significantly relationship (melanoma effect size=-0.511; p=2.41x10-5; size=-0.454; p=4.36x10-7; size=-0.489; p=5.59x10-10). Our results support causal these vitiligo, reveal potential therapeutic targets prevention effective treatment cancer.