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

• 批准号: 10356846
• 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: 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/10356846
• 关键词: Actinic keratosis; Adult; Affect; Age; Aging; American; Basal cell carcinoma; Behavior Therapy; Biological Process; Carcinoma; Cells; Chronic; Clinical; Clinical Markers; Code; Data; Development; Diagnosis; Disease; Environmental Exposure; Environmental Risk Factor; Etiology; Genetic; Genetic Risk; Genetic study; Health; Heritability; Histologic; Immunosuppression; Individual; Light; Malignant Epithelial Cell; Malignant Neoplasms; Medical Genetics; 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; base; 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; risk prediction; risk prediction model; risk sharing; risk variant; screening; sex; tool; tumor

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

修改的项目摘要/摘要部分 角质细胞癌（KC），由基底细胞癌和鳞状细胞癌组成 美国常见的恶性肿瘤，每年大约有300万美国人。治疗 KC是所有癌症中最昂贵的。基底细胞癌和鳞状细胞癌均得出 来自表皮角质形成细胞，但尽管共享相同的原始细胞，但这两个角质细胞癌 沿着不同的致癌途径发散。 KC的风险因素包括先天因素，例如遗传风险 基因座和色素沉着以及环境暴露，包括阳光暴露，吸烟和 免疫抑制。最近，遗传关联研究已开始揭示特定的遗传风险因素 基础KCS。但是，我们对这些KC遗传风险基因座中的哪个理解存在差距 一般会影响KC的风险，并影响对基底细胞癌和鳞状细胞的敏感性 癌癌，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 攻击性和高负担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（包括暴露，吸烟和免疫抑制）如何 影响这些风险。最后，我们将开发一个高负担KCS的风险预测模型，这是基于我们的 最近开发了用于CSCCSCORE鳞状细胞癌的风险预测工具。该工具将改善我们的 了解KC发病机理并有助于指导癌症筛查决策