Genome-wide association study of cutaneous squamous cell carcinoma

皮肤鳞状细胞癌的全基因组关联研究

• 批准号: 8817258
• 负责人: MARYAM Mandana ASGARI
• 金额: --
• 依托单位: KAISER FOUNDATION RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-03-01 至 2015-03-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8817258
• 关键词: Accounting; Actinic keratosis; Address; Affect; Age; American; Americas; Anatomy; Basal cell carcinoma; Baseline Surveys; Biopsy; California; Characteristics; Chronic; Clinical Markers; Cutaneous; Cutaneous Melanoma; DNA; Data; Databases; Development; Diagnosis; Disease; Electronic Health Record; Electronics; Enrollment; Environment; Environmental Health; Evaluation; First Degree Relative; Future; Gender; Genes; Genetic; Genetic Determinism; Genetic Predisposition to Disease; Genotype; Goals; Health; Histologic; Incidence; Investigation; Lesion; Malignant Neoplasms; Measures; Medical Genetics; Modeling; Not Hispanic or Latino; Pathology; Physicians; Pigmentation physiologic function; Population; Population Heterogeneity; Predisposition; Preventive; Publishing; Quality Control; Registries; Research; Resources; Risk; Risk Factors; Sample Size; Sampling; Single Nucleotide Polymorphism; Skin Cancer; Smoking; Squamous cell carcinoma; Stratification; Subgroup; Syndrome; Testing; Time; Ultraviolet Rays; United States; Variant; base; burden of illness; cancer risk; cohort; cost; gene environment interaction; genetic association; genetic resource; genome wide association study; genome-wide; improved; meetings; melanoma; member; programs; screening; skin squamous cell carcinoma; tumor

DESCRIPTION (provided by applicant): Cutaneous squamous cell carcinoma (SCC) is the second most common cancer in America, with over 700,000 cases diagnosed annually, and its incidence is on the rise. Despite the large population affected and resultant burden of disease, little is known about genetic determinants of SCCs. There are no published genome-wide association studies (GWAS) examining single nucleotide polymorphism (SNP) variants associated with SCC risk. The lack of published findings may be due, in part, to the fact that cutaneous SCCs are not reportable malignancies, and are therefore difficult to reliably identify. The electronic pathology databases at Kaiser Permanente Northern California (KNPC) overcome that barrier, and have been used to capture all biopsy-proven cutaneous SCCs from 1997 onward in a validated SCC registry. This project utilizes existing genetic data on over 675,000 SNPs from a large, well-characterized cohort of the Research Program on Genes, Environment and Health (RPGEH). The RPGEH has also collected comprehensive data including information on demographic and environmental variables on its cohort members. Using the unique resources of the RPGEH combined with the SCC Registry, we aim to perform a GWAS to identify SNP sequence variants associated with SCC risk on 77,578 non-Hispanic white RPGEH members, 5,953 of whom go on to develop at least one post-enrollment SCC. We will also test for interactions with established SCC risk factors, including pigmentation, gender, smoking, and actinic keratosis (a clinical marker for chronic ultraviolet light exposure). Furthermore, we will determine whether our identified SNP associations are stronger in subjects with multiple primary SCCs. In addition, we will evaluate whether there is any variation in SNP effects by tumor characteristics. Finally, we will compare our SNPs with those previously identified for BCCs and melanomas from published GWAS to attempt to identify genetic loci associated with skin cancer risk. Ultimately, we seek to improve our understanding of cutaneous SCCs and to identify mechanisms accounting for increased inherited susceptibility.

描述（申请人提供）：皮肤鳞状细胞癌（SCC）是美国第二大常见癌症，每年诊断出超过 700,000 例病例，且其发病率呈上升趋势。尽管受影响人口众多并造成疾病负担，但人们对鳞状细胞癌的遗传决定因素知之甚少。目前尚无已发表的全基因组关联研究 (GWAS) 来检查与 SCC 风险相关的单核苷酸多态性 (SNP) 变异。缺乏发表的研究结果可能部分是由于皮肤鳞状细胞癌不是可报告的恶性肿瘤，因此很难可靠地识别。北加州凯撒医疗机构 (KNPC) 的电子病理学数据库克服了这一障碍，自 1997 年起已用于在经过验证的 SCC 登记处捕获所有活检证明的皮肤 SCC。该项目利用来自基因、环境与健康研究计划 (RPGEH) 的大型、特征明确的队列中超过 675,000 个 SNP 的现有遗传数据。 RPGEH 还收集了全面的数据，包括其队列成员的人口统计和环境变量信息。利用 RPGEH 的独特资源与 SCC 注册中心相结合，我们的目标是进行 GWAS，以识别 77,578 名非西班牙裔白人 RPGEH 成员中与 SCC 风险相关的 SNP 序列变异，其中 5,953 人在注册后继续开发至少一种南卡罗来纳州。我们还将测试与已确定的鳞状细胞癌危险因素的相互作用，包括色素沉着、性别、吸烟和光化性角化病（慢性紫外线暴露的临床标志物）。此外，我们将确定我们发现的 SNP 关联在患有多个原发性 SCC 的受试者中是否更强。此外，我们将评估SNP效应是否因肿瘤特征而存在差异。最后，我们将把我们的 SNP 与之前从已发表的 GWAS 中确定的 BCC 和黑色素瘤的 SNP 进行比较，以尝试识别与皮肤癌风险相关的遗传位点。最终，我们寻求提高对皮肤鳞状细胞癌的了解，并确定遗传易感性增加的机制。