Data_Sheet_1_Identifying Susceptibility Loci for Cutaneous Squamous Cell Carcinoma Using a Fast Sequence Kernel Association Test.PDF

Cutaneous squamous cell carcinoma (cSCC) accounts for about 20% of all skin cancers, the most common type of malignancy in the United States. Genome-wide association studies (GWAS) have successfully identified multiple genetic variants associated with the risk of cSCC. Most of these studies were single-locus-based, testing genetic variants one-at-a-time. In this article, we performed gene-based association tests to evaluate the joint effect of multiple variants, especially rare variants, on the risk of cSCC by using a fast sequence kernel association test (fastSKAT). The study included 1,710 cSCC cases and 24,304 cancer-free controls from the Nurses’ Health Study, the Nurses’ Health Study II and the Health Professionals Follow-up Study. We used UCSC Genome Browser to define gene units as candidate loci, and further evaluated the association between all variants within each gene unit and disease outcome. Four genes HP1BP3, DAG1, SEPT7P2, and SLFN12 were identified using Bonferroni adjusted significance level. Our study is complementary to the existing GWASs, and our findings may provide additional insights into the etiology of cSCC. Further studies are needed to validate these findings.

皮肤鳞状细胞癌（cSCC）约占所有皮肤癌的20%，是美国最常见的恶性肿瘤。全基因组关联研究（GWAS）已成功识别出与cSCC风险相关的多个遗传变异。其中大部分研究基于单位点，逐一测试遗传变异。在本研究中，我们通过快速序列核关联测试（fastSKAT）对多个变异，尤其是罕见变异对cSCC风险的联合效应进行了基因关联测试。研究纳入了来自护士健康研究、护士健康研究II和健康专业人员随访研究的1,710例cSCC病例和24,304名无癌对照者。我们利用UCSC基因组浏览器定义基因单元为候选位点，并进一步评估了每个基因单元内所有变异与疾病结果之间的关联。通过Bonferroni校正显著性水平，识别出HP1BP3、DAG1、SEPT7P2和SLFN12四个基因。我们的研究补充了现有的GWAS，我们的发现可能为cSCC的病因学研究提供额外的见解。需要进一步的研究来验证这些发现。（Cutaneous squamous cell carcinoma (cSCC), Genome-wide association studies (GWAS), Gene-based association tests, fast sequence kernel association test (fastSKAT), UCSC Genome Browser, Candidate loci, Disease outcome, Bonferroni adjusted significance level）