Gene-environment Cancer Risks in Melanoma

黑色素瘤的基因-环境癌症风险

• 批准号: 7265141
• 负责人: Melissa Gonzales
• 金额: $ 12.02万
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7265141
• 关键词: Affect; Area; Australia; Base Excision Repairs; CDC2 Protein Kinase; Canada; Case-Control Studies; Cells; Chronic; Complex; DNA; DNA Library; DNA Repair; Data; Development; Development Plans; Disease; Enrollment; Environment; Environmental Health; Environmental Risk Factor; Epidemiologic Studies; Evaluation; Exposure to; Genes; Genetic; Genetic Polymorphism; Genotype; Goals; Hand; Incidence; Inpatients; Interdisciplinary Study; International; Interview; Italy; K-Series Research Career Programs; Laboratories; Logistics; Metric; Mexico; Molecular; Molecular Biology; Molecular Epidemiology; Molecular Genetics; Nucleotide Excision Repair; Occupational; Occupational Exposure; Outcome; Pathway interactions; Penetrance; Population; Positioning Attribute; Prevalence; Radiation Genetics; Recording of previous events; Regression Analysis; Research; Research Personnel; Research Proposals; Risk; Sampling; Secondary to; Specimen; Study models; Sun Exposure; Techniques; Testing; Training; UV Radiation Exposure; Ultraviolet Rays; United States; Universities; Variant; base; cancer risk; career; case control; gene environment interaction; gene interaction; gene repair; genetic epidemiology; melanoma; multidisciplinary; novel; programs; skills; theories

DESCRIPTION (provided by applicant) The goal of this career development plan is to launch an independent research program in molecular epidemiology with specific emphasis on the evaluation of gene-environment interactions. To this end, it includes both didactic coursework and hands-on training in the areas of molecular biology/ genetics and molecular epidemiology. Melanoma is a unique model for studying gene-environment interactions as there is mounting evidence that low-penetrance genetic polymorphisms may moderate the melanoma risk of solar UV exposure. Genes of the base excision repair (BER) pathway repair DNA damage secondary to UVA exposure. The candidate will use the international Genes, Environment and Melanoma (GEM) 3366-subject case-control study as a platform to test the hypothesis that UV radiation and BER variants interactively affect melanoma risk. Lifetime sun exposure history and DNA specimens are available for each subject. The candidate's research will (a) determine the prevalence of BER variants in GEM melanoma cases and controls; (b) evaluate the interactive influence of candidate BER variants and chronic sun exposure on melanoma risk; and (c) investigate whether melanoma risk is influenced by gene-gene interactions between BER variants and variants in other genes currently being examined in the GEM study (MC1R and nucleotide excision repair genes) adjusting for sun exposure. This research proposal will provide the candidate with an appreciation for and understanding of the laboratory and epidemiologic analyses techniques needed to conduct molecular epidemiologic research on environmentally related diseases. Through intensive interactions with the GEM consortium and other multidisciplinary investigators, formal coursework in molecular biology and epidemiology, and research, this career development award will establish the candidate's multidisciplinary research skills at the interface of genetics, epidemiology and environmental health, and position her to establish novel theories regarding the mechanisms underlying complex genetic-environmental interactions in melanoma.

描述（由申请人提供） 该职业发展计划的目的是启动一项独立的分子流行病学研究计划，并特别强调对基因环境相互作用的评估。为此，它包括分子生物学/遗传学和分子流行病学领域的教学课程和动手培训。 黑色素瘤是研究基因环境相互作用的独特模型，因为有越来越多的证据表明，低渗透遗传多态性可能会减轻黑色素瘤暴露的黑色素瘤风险。 基础切除修复基因（BER）途径修复了继发于UVA暴露的DNA损伤。 候选人将使用国际基因，环境和黑色素瘤（GEM）3366-Auspign-subject病例对照研究作为一个平台，以测试紫外线辐射和BER变体的假设，即交互影响黑色素瘤风险。 每个受试者都可以使用终生的太阳暴露历史和DNA标本。 候选人的研究将（a）确定宝石黑色素瘤病例和对照中BER变体的普遍性； （b）评估候选人BER变体和慢性太阳暴露对黑色素瘤风险的互动影响； （c）研究黑色素瘤风险是否受到GEM研究中当前正在检查的其他基因（MC1R和核苷酸切除修复基因）中的其他基因之间的基因 - 基因相互作用的影响，以调整日晒暴露。 这项研究建议将为候选人提供对实验室和流行病学分析的理解和理解，以进行有关环境相关疾病的分子流行病学研究所需的技术。通过与GEM财团和其他多学科研究人员的密集互动，分子生物学和流行病学的正式课程以及研究，该职业发展奖将在遗传学，流行病学和环境健康的界面上建立候选人的多学科研究技能关于黑色素瘤中复杂遗传环境相互作用的机制的新理论。