Genetic Variants in MicroRNA-Related Genes and Skin Cancer Risk

MicroRNA 相关基因的遗传变异与皮肤癌风险

• 批准号: 7658431
• 负责人: Hongmei Nan
• 金额: $ 8.85万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7658431
• 关键词: Apoptosis; Basal cell carcinoma; Biogenesis; Biological Process; Blood; Cell Cycle; Cell Cycle Arrest; Cell Proliferation; Characteristics; Code; Constitutional; DNA; DNA Damage; DNA Repair; Development; Evaluation; Functional RNA; Gene Expression; Gene Targeting; Genes; Genetic Polymorphism; Genetic Variation; Immune response; Immunosuppression; Individual; Inherited; Integration Host Factors; Malignant Neoplasms; MicroRNAs; Nested Case-Control Study; Nucleotides; Nurses' Health Study; Play; Proto-Oncogenes; Questionnaires; Recording of previous events; Regulation; Research; Resources; Risk; Risk Factors; Risk Management; Role; Sampling; Skin; Skin Cancer; Skin Carcinoma; Squamous cell carcinoma; Suppressor Genes; Testing; Tumor Suppressor Genes; Ultraviolet Rays; Untranslated Regions; Variant; Work; base; cancer risk; cohort; design; follow-up; genetic variant; high risk; innovation; melanoma; promoter; prospective; response; tumorigenesis

DESCRIPTION (provided by applicant): Substantial biologic evidence indicates that microRNAs may play crucial role in development of cancer by regulating their target genes that control biological processes, such as cell cycle, cell proliferation, differentiation, and apoptosis. However, the importance of common inherited variants in microRNA-related genes and their interactions with constitutional host factors and UV exposure history in causing skin cancer is largely unknown. We propose to examine in detail the associations of genetic variants in microRNA-related genes with the risk of melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) simultaneously in a nested case-control study within the Nurses Health Study (219 melanoma cases, 286 SCC cases, 300 BCC cases, and 874 matched controls). This innovative work will move this field forward, by evaluating common variants using complementary approaches, i.e. to evaluate putative functional SNPs and to choose tag- SNPs to test for associations of unknown common functional variants with skin cancer risk. In addition, we will also assess the interactions between genetic variants in these genes and constitutional host factors and UV exposure history on skin cancer risk. This proposal will take advantage of the research opportunities nested within the existing well-characterized cohort, including cohort characteristics, quality of design, high follow-up rate, rigor in prospective host risk factor assessment, and high response rate of retrospective questionnaires. Our study will also take advantage of the previously confirmed cases of the three types of skin cancers, stored blood and DNA samples, as well as previously collected information on host risk factors and UV exposure history. This research will contribute to the scientific basis for identifying high-risk individuals for skin cancer and providing individualized risk management strategies.

描述（由申请人提供）：大量的生物学证据表明，microRNA可以通过调节控制生物学过程的靶基因，例如细胞周期，细胞增殖，分化和凋亡。然而，普通遗传变体在与microRNA相关基因中的重要性及其与宪法宿主因子和紫外线暴露史的相互作用在引起皮肤癌中的重要性是未知的。我们建议详细检查与MicroRNA相关基因中遗传变异的关联与黑色素瘤，鳞状细胞癌（SCC）（SCC）和基底细胞癌（BCC）的风险，同时在护士健康研究中嵌套的病例对照研究（ 219例黑色素瘤病例，286例SCC病例，300例BCC病例和874例匹配对照。这项创新的工作将通过使用互补方法来评估常见变体，即评估推定的功能SNP并选择TAG-SNP来测试未知常见的功能变体与皮肤癌风险的未知相关性。此外，我们还将评估这些基因中的遗传变异与宪法宿主因素与皮肤癌风险的紫外线暴露史之间的相互作用。该提案将利用嵌套在现有良好表征的队列中的研究机会，包括队列特征，设计质量，高后续率，预期寄主风险因素评估的严格性以及回顾性问卷的高回应率。我们的研究还将利用先前确认的三种类型的皮肤癌，储存的血液和DNA样品的病例，以及先前收集的有关宿主风险因素和紫外线暴露病史的信息。这项研究将有助于科学基础，以确定皮肤癌的高风险个体并提供个性化的风险管理策略。