Genetic Variants in Pigmentation Genes and Skin Cancer Risk

色素沉着基因的遗传变异与皮肤癌风险

• 批准号: 7264926
• 负责人: JIALI HAN
• 金额: $ 8.75万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7264926
• 关键词: Basal cell carcinoma; Blood; Burn injury; Characteristics; Code; Constitutional; Count; DNA; Data; Eye Color; Genes; Genetic Polymorphism; Genetic Variation; Hair Color; Haplotypes; Health; Human; Individual; Inherited; Integration Host Factors; Melanocortin 1 Receptor; Melanocytic nevus; Mole the mammal; Monophenol Monooxygenase; Nested Case-Control Study; Nurses' Health Study; POMC gene; Pathway interactions; Pigmentation physiologic function; Play; Principal Investigator; Pro-Opiomelanocortin; Questionnaires; Rate; Recording of previous events; Research; Resources; Risk; Risk Factors; Risk Management; Role; Sample Size; Sampling; Skin Cancer; Skin tanning; Squamous cell carcinoma; TYR gene; Testing; Tyrosine; Untranslated Regions; Variant; Work; base; cancer risk; cohort; design; follow-up; genetic variant; human TYRP1 protein; innovation; melanoma; programs; prospective; response; skin color; ultraviolet

DESCRIPTION (provided by applicant): Substantial biologic evidence indicates that the pigmentation pathway plays a critical role in protecting against skin cancer. However, the importance of common inherited variants in the pigmentation pathway and their interactions with constitutional host factors and UV exposure history in causing skin cancer is largely unknown. Sparse data exist except for the melanocortin 1 receptor (MC1R) genetic variants. We propose to examine in detail the genetic variants in the pigmentation pathway with the risks 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 in the pigmentation pathway 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, along with exploratory pathway analyses. 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, large sample size, 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色素沉着途径在预防皮肤癌方面发挥着关键作用。然而，色素沉着途径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。除黑皮质素 1 受体 (MC1R) 遗传变异外，存在稀疏数据。我们建议在护士健康研究（219 例黑色素瘤病例）中的一项巢式病例对照研究中，同时详细检查色素沉着途径中的遗传变异与黑色素瘤、鳞状细胞癌 (SCC) 和基底细胞癌 (BCC) 的风险。 、286 例 SCC 病例、300 例 BCC 病例和 874 例匹配对照）。这项创新工作将推动这一领域向前发展，通过使用补充方法评估色素沉着途径中的常见变异，即评估假定的功能性 SNP 并选择标签 SNP 来测试未知的常见功能变异与皮肤癌风险的关联，以及探索性的路径分析。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、大样本量、前瞻性宿主风险因素评估的严格性以及回顾性的高响应率问卷调查。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。