Gene-environment Cancer Risks in Melanoma

黑色素瘤的基因-环境癌症风险

• 批准号: 7117671
• 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/7117671
• 关键词: DNA damage; DNA repair; cancer risk; clinical research; environmental exposure; gene environment interaction; gene interaction; genetic polymorphism; human genetic material tag; human subject; longitudinal human study; melanoma; neoplasm /cancer genetics; questionnaires; ultraviolet radiation

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） 这个职业发展计划的目标是启动一个独立的分子流行病学研究计划，特别强调基因-环境相互作用的评估。为此，它包括教学课程和动手训练在分子生物学/遗传学和分子流行病学领域。 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，低突变率的遗传多态性可能会降低太阳紫外线暴露的黑色素瘤风险。 碱基切除修复（BER）途径的基因修复UVA暴露继发的DNA损伤。 候选人将使用国际基因，环境和黑色素瘤（GEM）3366受试者病例对照研究作为平台，以检验紫外线辐射和BER变体交互影响黑色素瘤风险的假设。 每个受试者都有一生的阳光照射史和DNA标本。 候选人的研究将（a）确定BER变异在GEM黑色素瘤病例和对照中的患病率;（B）评估候选BER变异和慢性日光暴露对黑色素瘤风险的交互影响;以及（c）研究黑色素瘤风险是否受到BER变异体和GEM研究中目前正在检查的其他基因中的变异体之间的基因-基因相互作用的影响（MC 1 R和核苷酸切除修复基因）调整阳光照射。 该研究计划将为候选人提供对进行环境相关疾病分子流行病学研究所需的实验室和流行病学分析技术的理解和理解。通过与GEM联盟和其他多学科研究人员的密切互动，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，并使她能够建立关于黑色素瘤中复杂的遗传-环境相互作用机制的新理论。