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The Role of Genetic Risk Factors in Keratinocyte Carcinoma Susceptibility

遗传危险因素在角质形成细胞癌易感性中的作用

基本信息

批准号：
10606627
负责人：
MARYAM Mandana ASGARI
金额：
$ 39.66万
依托单位：
KAISER FOUNDATION RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-03-01 至 2026-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10606627
关键词：
Actinic keratosis Adult Affect Age Aging American Basal cell carcinoma Behavior Therapy Biological Process Carcinoma Cells Chronic Classification Clinical Clinical Markers Code Data Development Diagnosis Disease Environmental Exposure Environmental Risk Factor Etiology Genetic Genetic Risk Genetic study Health Heritability Histologic Immunosuppression Individual Invaded Light Malignant Epithelial Cell Malignant Neoplasms Modification Oncogenic Participant Pathogenesis Pathway interactions Phenotype Physicians Pigmentation physiologic function Predisposition Prevention Probability Recording of previous events Records Recurrence Registries Risk Risk Factors Role Screening for cancer Smoker Smoking Smoking Behavior Squamous cell carcinoma Subgroup Sun Exposure Tumor Burden UV Radiation Exposure Ultraviolet Rays United States Variant Work biobank cell type clinical effect cohort cost experience genetic association genetic epidemiology genetic resource genetic risk factor genetic variant genome-wide genomic locus high risk improved in silico innovation insight keratinocyte neoplasm registry never smoker non-genetic perineural predictive modeling predictive tools risk prediction risk prediction model risk sharing risk variant screening sex tool tumor

项目摘要

Modified Project Summary/Abstract Section Keratinocyte carcinoma (KC), comprised of basal cell carcinoma and squamous cell carcinoma, is the most common malignancy in the United States, afflicting approximately 3 million Americans annually. The treatment of KCs is among the most costly of all cancers. Both basal cell carcinoma and squamous cell carcinoma derive from epidermal keratinocytes, but despite sharing the same cell of origin, these two keratinocyte carcinomas diverge along distinct oncogenic pathways. Risk factors for KCs include innate factors, such as genetic risk loci and fair pigmentation, and environmental exposures, including sun exposure, smoking, and immunosuppression. Recently, genetic association studies have begun to reveal specific genetic risk factors underlying KCs. However, there remains a gap in our understanding of which of these KC genetic risk loci affect the risk of KC in general and which affect susceptibility to basal cell carcinoma and squamous cell carcinoma specifically, how these loci are influenced by environmental exposures, and how these loci impact aggressive and high burden KCs. This study will determine whether KC genetic risk loci have effects that are specific to basal cell carcinoma or squamous cell carcinoma, or are shared across these two types of KC. We will further evaluate how environmental factors, including sun exposure, smoking, and immunosuppression influences these risks. Finally, we will develop a risk prediction model of high burden KCs, that builds on our recently developed risk prediction tool for squamous cell carcinoma, cSCCscore. This tool will improve our understanding of KC pathogenesis and help guide cancer screening decisions

修改后的项目摘要/摘要部分角质形成细胞癌(KC)由基底细胞癌和鳞状细胞癌组成，是最常见的恶性肿瘤美国常见的恶性肿瘤，每年约有300万美国人罹患此病。治疗方法 KC是所有癌症中最昂贵的癌症之一。基底细胞癌和鳞状细胞癌均起源于来自表皮角质形成细胞，但尽管有相同的起源细胞，这两种角质形成细胞癌沿着不同的致癌途径分叉。KC的风险因素包括先天因素，如遗传风险基因座和正常的色素沉着，以及环境暴露，包括阳光照射，吸烟，和免疫抑制。最近，遗传关联研究已经开始揭示特定的遗传风险因素。底层KC。然而，在我们对这些KC遗传风险基因座中的哪一个的理解上仍然存在差距总体上影响KC的风险，并影响对基底细胞癌和鳞状细胞癌的易感性尤其是癌症，这些基因座如何受到环境暴露的影响，以及这些基因座如何影响攻击性强、负担重的KCs。这项研究将确定KC遗传风险基因座是否具有特定于基底细胞癌或鳞状细胞癌，或在这两种类型的KC中共享。我们将进一步评估环境因素，包括阳光照射、吸烟和免疫抑制会影响这些风险。最后，我们将开发一个高负担KC的风险预测模型，该模型建立在我们的最近开发的鳞状细胞癌风险预测工具cSCCcore。此工具将改进我们的了解KC的发病机制并帮助指导癌症筛查决策