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: 7793479
• 负责人: Hongmei Nan
• 金额: $ 8.9万
• 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 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7793479
• 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）：大量生物学证据表明，microRNA 可能通过调节控制细胞周期、细胞增殖、分化和凋亡等生物过程的靶基因，在癌症的发展中发挥至关重要的作用。然而，microRNA 相关基因中常见遗传变异的重要性及其与宿主因素和紫外线暴露史的相互作用在导致皮肤癌中的重要性尚不清楚。我们建议在护士健康研究中的一项巢式病例对照研究中同时详细检查 microRNA 相关基因的遗传变异与黑色素瘤、鳞状细胞癌 (SCC) 和基底细胞癌 (BCC) 风险的关联。 219 例黑色素瘤病例、286 例鳞状细胞癌病例、300 例基底细胞癌病例和 874 例匹配对照）。这项创新工作将通过使用补充方法评估常见变异来推动这一领域向前发展，即评估假定的功能性 SNP 并选择标签 SNP 来测试未知常见功能变异与皮肤癌风险的关联。此外，我们还将评估这些基因的遗传变异与宿主因素和紫外线暴露史之间的相互作用对皮肤癌风险的影响。该提案将利用现有特征明确的队列中的研究机会，包括队列特征、设计质量、高随访率、严格的前瞻性宿主风险因素评估以及回顾性问卷的高回复率。我们的研究还将利用先前确诊的三种皮肤癌病例、储存的血液和DNA样本，以及先前收集的有关宿主危险因素和紫外线暴露史的信息。这项研究将为识别皮肤癌高危人群和提供个性化风险管理策略奠定科学基础。