Genome-wide meta-analysis identifies eight new susceptibility loci for cutaneous squamous cell carcinoma
Kavita Y. Sarin, Yuan Lin, Roxana Daneshjou, Andrey Ziyatdinov, Guðmar Þorleifsson, Adam J. Rubin, Luba M. Pardo, Wenting Wu, Paul A. Khavari, André G. Uitterlinden, Tamar Nijsten, Amanda E. Toland, Jón Ólafsson, Bárður Sigurgeirsson, Kristin Thorisdottir, Eric Jörgensen, Alice S. Whittemore, Peter Kraft, Simon Stacey, Kāri Stefánsson, Maryam M. Asgari, Jiali Han
Abstract
Cutaneous squamous cell carcinoma (SCC) is one of the most common cancers in the United States. Previous genome-wide association studies (GWAS) have identified 14 single nucleotide polymorphisms (SNPs) associated with cutaneous SCC. Here, we report the largest cutaneous SCC meta-analysis to date, representing six international cohorts and totaling 19,149 SCC cases and 680,049 controls. We discover eight novel loci associated with SCC, confirm all previously associated loci, and perform fine mapping of causal variants. The novel SNPs occur within skin-specific regulatory elements and implicate loci involved in cancer development, immune regulation, and keratinocyte differentiation in SCC susceptibility.