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

基本信息

批准号：
8440111
负责人：
MARYAM Mandana ASGARI
金额：
$ 29.65万
依托单位：
KAISER FOUNDATION RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-03-01 至 2017-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8440111
关键词：
Accounting Actinic keratosis Address Affect Age American Americas Anatomic Sites Basal cell carcinoma Baseline Surveys Biopsy California Characteristics Chronic Clinical 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 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 public health relevance screening skin squamous cell carcinoma tumor

项目摘要

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（由申请人提供）：皮肤鳞状细胞癌（SCC）是美国第二常见的癌症，每年被诊断出70万例病例，其发病率正在上升。尽管人口受影响很大和疾病负担，但对SCC的遗传决定因素知之甚少。没有公开的全基因组关联研究（GWAS）检查与SCC风险相关的单核苷酸多态性（SNP）变体。缺乏已发表的发现可能部分是由于皮肤SCC不是可报告的，因此很难可靠地识别。 Kaiser Permanente North California（KNPC）的电子病理数据库克服了该障碍，并已在经过验证的SCC注册表中从1997年开始捕获所有证实的皮肤SCC。该项目利用了来自大型，良好的基因，环境与健康研究计划（RPGEH）的大型，良好的人群中的675,000个SNP的现有遗传数据。 RPGEH还收集了全面的数据，包括有关其队列成员的人口统计和环境变量的信息。使用RPGEH的独特资源与SCC注册表相结合，我们旨在执行GWAS，以识别77,578个非西班牙裔白色RPGEH成员与SCC风险相关的SNP序列变体，其中有5,953名继续开发至少一个Enrollment Enrollment SCC。我们还将测试与已建立的SCC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，我们将确定在具有多个主要SCC的受试者中所识别的SNP关联是否更强。此外，我们将评估SNP效应是否因肿瘤特征存在任何差异。最后，我们将将我们的SNP与先前针对BCC和黑色素瘤鉴定出的GWA的SNP进行比较，以试图鉴定与皮肤癌风险相关的遗传基因座。最终，我们试图提高对皮肤SCC的理解，并确定遗传易感性增加的机制。