Genetic epidemiology of early-onset basal cell carcinoma

早发性基底细胞癌的遗传流行病学

基本信息

批准号：
8107696
负责人：
Allen Everett Bale
金额：
$ 8.03万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-08 至 2012-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8107696
关键词：
Accounting Age Basal cell carcinoma Behavior Therapy Candidate Disease Gene Circadian Rhythms Collaborations Collection Constitutional Cost Analysis DNA DNA Damage DNA Repair Gene DNA Sequence Data Disease Environmental Risk Factor Epidemiologic Studies Exons Future Gene Mutation Genes Genetic Genetic Predisposition to Disease Genetic Risk Grant Individual Inherited Intention Measures Medical Modeling Mutation Nature Oculocutaneous Albinism Pigments Predisposition Preventive Public Health Risk Role Route Sampling Skin Skin Cancer Study Subject Testing Time Study Translating UV Radiation Exposure UV induced UV induced DNA damage Variant Xeroderma Pigmentosum cancer risk cancer type early onset genetic epidemiology genetic variant human disease melanoma public health relevance repaired skin cancer prevention skin color theories

项目摘要

DESCRIPTION (provided by applicant): Most human diseases result from the interplay of hereditary and environmental factors. The nature of the genetic component in common disorders is a subject of some debate. There are proponents for a model in which a few common genetic variants have weak effects, which add up to a significant attributable genetic risk. On the other hand it is possible that many different rare genetic mutations, each with a strong effect, in aggregate account for disease in a high proportion of people. An ongoing project supported by the Yale Skin Cancer SPORE Grant involves analysis of the roles of hereditary and environmental factors and the interaction between these factors in the risk for early-onset basal cell carcinoma of the skin (below age 40). The SPORE supports collection of broad demographic, ethnic, and environmental risk factor data as well as DNA samples from 500 cases and 500 controls. Sequencing of MC1R, a small (one-exon) skin pigment gene in all subjects is also supported. At the time the study was conceived, the cost of analysis of additional genes was prohibitively expensive. More recent introduction of high- throughput platforms for DNA sequencing will allow for querying many genes for mutations that may be associated with skin cancer risk. The aim of this application is use high-throughput platforms for sequencing constitutional DNA from 100 cases and 100 controls. This project will cast a wide net, examining all known major skin pigment genes, all genes closely associated with repair of UV-induced DNA damage, and circadian rhythm genes that may be associated with cancer risk. The intention is to generate preliminary data from this subset of study subjects to support applications for future large grants that would allow us to test all of our subjects for promising candidate genes and, in collaboration with other groups, examine these genes in additional skin cancer cases. Discovering an underlying genetic predisposition may help tailor preventive measures and "personalize" medical treatment. The well established role of UV exposure as an environmental risk factor for skin cancer provides a route to translate our analyses into public health approaches to better prevent skin cancer. In theory, individuals with a genetic predisposition to this cancer type could be targeted for behavior modification. PUBLIC HEALTH RELEVANCE: Discovering an underlying genetic predisposition to skin cancer may help tailor preventive measures and "personalize" medical treatment. The well established role of UV exposure as an environmental risk factor for skin cancer provides a route to translate our analyses into public health approaches to better prevent skin cancer. In theory, individuals with a genetic predisposition to this cancer type could be targeted for behavior modification.

描述（由申请人提供）：大多数人类疾病是由遗传和环境因素的相互作用引起的。常见疾病中遗传成分的性质是一些辩论的主题。有一些模型的支持者，其中一些常见的遗传变异具有较弱的作用，这加起来构成了可观的遗传风险。另一方面，可能有许多不同的稀有遗传突变，每种突变都具有很强的作用，总体上以很大一部分的人说明了疾病。由耶鲁大学皮肤癌孢子赠款支持的持续项目涉及分析遗传和环境因素的作用，以及这些因素之间在皮肤早期发作的基底细胞癌风险中的相互作用（低于40岁）。孢子支持收集广泛的人口，种族和环境风险因素数据以及500例和500个对照的DNA样本。还支持MC1R的测序，MC1R是所有受试者中的小（单位）皮肤色素基因。在构思研究时，对其他基因的分析成本非常昂贵。最近引入用于DNA测序的高吞吐量平台将允许查询许多基因可能与皮肤癌风险相关的突变。该应用程序的目的是使用高通量平台来对100例和100个对照的宪法DNA进行测序。该项目将投入宽阔的网络，检查所有已知的主要皮肤色素基因，所有基因与紫外线诱导的DNA损伤的修复密切相关，以及可能与癌症风险相关的昼夜节律基因。目的是从该研究对象中生成初步数据，以支持未来的大笔赠款的应用，这将使我们能够测试所有受试者有希望的候选基因，并与其他小组合作，在其他皮肤癌病例中检查这些基因。发现潜在的遗传易感性可能有助于量身定制预防措施并“个性化”医疗。紫外线暴露作为皮肤癌的环境风险因素的良好作用为将我们的分析转化为公共卫生方法，以更好地预防皮肤癌。从理论上讲，对这种癌症类型的遗传易感性的个体可以针对行为改变。公共卫生相关性：发现对皮肤癌的潜在遗传易感性可能有助于量身定制预防措施并“个性化”医疗。紫外线暴露作为皮肤癌的环境风险因素的良好作用为将我们的分析转化为公共卫生方法，以更好地预防皮肤癌。从理论上讲，对这种癌症类型的遗传易感性的个体可以针对行为改变。