Identifying Susceptibility Loci for Cutaneous Squamous Cell Carcinoma Using a Fast Sequence Kernel Association Test.
Identifying Susceptibility Loci for Cutaneous Squamous Cell Carcinoma Using a Fast Sequence Kernel Association Test.
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DOI：
10.3389/fgene.2021.657499
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发表时间：
2021
影响因子：
3.7
通讯作者：
Li M
中科院分区：
文献类型：
--
作者：
Huang M;Lyu C;Li X;Qureshi AA;Han J;Li M
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类型。全基因组关联研究（GWAS）已成功识别出与cSCC风险相关的多种遗传变异。这些研究大多数是基于单位点的，一次测试一个遗传变异。在这篇文章中，我们进行了基于基因的关联检验，以评估多种变异，特别是罕见变异，对cSCC风险的联合作用，通过使用快速序列核关联检验（fastSKAT）。该研究包括来自护士健康研究，护士健康研究II和卫生专业人员随访研究的1，710例cSCC病例和24，304例无癌症对照。我们使用UCSC基因组浏览器将基因单位定义为候选基因座，并进一步评估每个基因单位内的所有变异与疾病结果之间的关联。使用Bonferroni调整的显著性水平鉴定了四个基因HP1BP3、DAG1、SEPT7P2和SLFN 12。我们的研究是对现有GWAS的补充，我们的研究结果可能会为cSCC的病因提供更多的见解。需要进一步的研究来验证这些发现。
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.
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影响因子：
30.8
作者：
Lee D;Gorkin DU;Baker M;Strober BJ;Asoni AL;McCallion AS;Beer MA
通讯作者：
Beer MA
影响因子：
30.8
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作者：
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影响因子：
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Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
3.7
作者：
Lindstrom, Sara;Loomis, Stephanie;Kraft, Peter
通讯作者：
Kraft, Peter