Prospective study of telomere length and melanoma risk

端粒长度和黑色素瘤风险的前瞻性研究

• 批准号: 7473580
• 负责人: JIALI HAN
• 金额: $ 8.78万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7473580
• 关键词: Age; Aging; Biological Assay; Biological Markers; Biological Process; Blood; Blood specimen; Burn injury; Characteristics; Cutaneous Melanoma; DNA; DNA Damage; Disease; Disruption; Evaluation; Genes; Genetic; Genetic Variation; Individual; Inherited; Length; Leukocytes; Maintenance; Malignant Neoplasms; Nurses' Health Study; Observational Study; Prospective Studies; Rate; Research; Risk; Risk Factors; Risk Management; Sample Size; Sampling; Skin Tissue; TERF1 gene; TERT gene; TINF2 gene; TNKS gene; Tankyrase; Telomere Shortening; Ultraviolet B Radiation; Variant; Woman; Women' s Health; abstracting; age related; base; cohort; design; follow-up; genetic variant; irradiation; melanoma; peripheral blood; prospective; response; telomere

DESCRIPTION (provided by applicant): Abstract: Prospective study of telomere length and melanoma risk Telomere length in peripheral blood leukocytes (PBLs) has emerged as a potential biomarker of aging and of risk of age-related diseases such as cancers. Telomere length is determined in part by inherited genetic factors. In addition to causing DNA damage, UVB irradiation shortens telomeres. In skin tissue, telomere disruption triggers multiple DNA damage responses. We propose to examine telomere length and genetic variants in telomere-related genes in relation to the risk of cutaneous malignant melanoma (hereafter called melanoma). We will include 586 incident cases of melanoma and 586 matched controls who provided blood samples pre-diagnostically from three large well- characterized cohorts, the Women's Health Initiative Observational Study, the Nurses Health Study, and Nurses Health Study II. In addition, we will assess the interactions between telomere length and genetic variants in telomere-related genes and tendency to burn/tan on melanoma risk. This application will take advantage of the research opportunities nested within the existing well-characterized cohort, including cohort characteristics, quality of design, high follow-up rate, and large sample size. Our study will also take advantage of the previously confirmed cases of melanoma, stored blood and DNA samples, as well as previously collected information on host risk factors. To date, no one has evaluated how telomere length or genetic variation in telomere-related genes may influence melanoma risk. In this study, we will examine whether the risk of melanoma is higher in women with shorter telomeres and is influenced by variation in genes related to telomere stability and maintenance. Establishing the relationship between telomere length in pre-diagnostically collected peripheral blood leukocytes and melanoma risk will be important for several reasons. It would provide corroboration for the hypothesis that biological processes related to aging are important determinants of melanoma risk and may provide an assay to be used part of an assessment of melanoma risk. This research will contribute to the scientific basis for identifying individuals at high risk for melanoma and providing individualized risk management strategies. Project Narrative: We propose a prospective evaluation of telomere length and the genetic variants in telomere-related genes in relation to the risk of cutaneous malignant melanoma. Establishing the relationship between telomere length in pre-diagnostically collected peripheral blood leukocytes and melanoma risk will be important for several reasons. It would provide corroboration for the hypothesis that biological processes related to aging are important determinants of melanoma risk and may provide an assay to be used part of an assessment of melanoma risk. This research will contribute to the scientific basis for identifying individuals at high risk for melanoma and providing individualized risk management strategies.

描述（由申请人提供）： 摘要：端粒长度和黑色素瘤风险的前瞻性研究外周血白细胞（PBL）中的端粒长度已成为衰老和癌症等年龄相关疾病风险的潜在生物标志物。端粒长度部分由遗传因素决定。 UVB 照射除了造成 DNA 损伤外，还会缩短端粒。在皮肤组织中，端粒破坏会引发多种 DNA 损伤反应。我们建议检查端粒长度和端粒相关基因的遗传变异与皮肤恶性黑色素瘤（以下称为黑色素瘤）风险的关系。我们将纳入 586 例黑色素瘤病例和 586 例匹配对照，这些对照提供了来自三个特征明确的大型队列（妇女健康倡议观察研究、护士健康研究和护士健康研究 II）的诊断前血液样本。此外，我们将评估端粒长度和端粒相关基因的遗传变异之间的相互作用，以及晒伤/晒黑倾向对黑色素瘤风险的影响。该应用程序将利用现有特征良好的队列中的研究机会，包括队列特征、设计质量、高随访率和大样本量。我们的研究还将利用先前确诊的黑色素瘤病例、储存的血液和 DNA 样本，以及先前收集的有关宿主危险因素的信息。迄今为止，没有人评估端粒长度或端粒相关基因的遗传变异如何影响黑色素瘤风险。在这项研究中，我们将检查端粒较短的女性患黑色素瘤的风险是否较高，并且是否受到与端粒稳定性和维持相关的基因变异的影响。出于多种原因，建立诊断前收集的外周血白细胞中端粒长度与黑色素瘤风险之间的关系非常重要。它将为以下假设提供佐证：与衰老相关的生物过程是黑色素瘤风险的重要决定因素，并可能提供一种用于评估黑色素瘤风险的检测方法。这项研究将为识别黑色素瘤高风险个体并提供个性化风险管理策略奠定科学基础。项目叙述：我们建议对端粒长度和端粒相关基因的遗传变异与皮肤恶性黑色素瘤风险的关系进行前瞻性评估。出于多种原因，建立诊断前收集的外周血白细胞中端粒长度与黑色素瘤风险之间的关系非常重要。它将为以下假设提供佐证：与衰老相关的生物过程是黑色素瘤风险的重要决定因素，并可能提供一种用于评估黑色素瘤风险的检测方法。这项研究将为识别黑色素瘤高风险个体并提供个性化风险管理策略奠定科学基础。