Identifying Susceptibility Loci for Cutaneous Squamous Cell Carcinoma Using a Fast Sequence Kernel Association Test.

Area of Science:

• Genetics
• Oncology
• Dermatology

Background:

• Cutaneous squamous cell carcinoma (cSCC) is a prevalent skin cancer in the US.
• Previous genome-wide association studies (GWAS) primarily used single-locus methods.
• Identifying genetic variants associated with cSCC risk is crucial for understanding its etiology.

Purpose of the Study:

• To evaluate the joint effect of multiple genetic variants, including rare ones, on cSCC risk.
• To perform gene-based association tests for cSCC risk loci.
• To complement existing single-locus GWAS findings in cSCC.

Main Methods:

• Utilized the fast sequence kernel association test (fastSKAT) for gene-based analysis.
• Analyzed data from 1,710 cSCC cases and 24,304 cancer-free controls from three large cohorts.
• Defined gene units using UCSC Genome Browser and assessed variants within each unit.

Main Results:

• Identified four genes (HP1BP3, DAG1, SEPT7P2, SLFN12) associated with cSCC risk.
• Applied Bonferroni correction for statistical significance.
• Findings suggest a role for these genes in cSCC etiology.

Conclusions:

• Gene-based association tests provide complementary insights to single-locus GWAS for cSCC.
• The identified genes may offer new avenues for understanding cSCC development.
• Further research is necessary to validate these genetic associations.