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：周围血清细胞（PBL）中端粒长度和黑色素瘤风险端粒长度的前瞻性研究已成为衰老的潜在生物标志物和与年龄相关疾病（如癌症）的风险。端粒长度部分由遗传因素确定。除了引起DNA损伤外，UVB辐射还缩短了端粒。在皮肤组织中，端粒破坏会触发多个DNA损伤反应。我们建议检查与皮肤恶性黑色素瘤的风险有关的端粒相关基因的端粒长度和遗传变异（以下称为黑色素瘤）。我们将包括586例黑色素瘤事件和586个匹配的对照组，这些对照可从三个大型特征良好的同类群体，妇女健康计划观察性研究，护士健康研究和护士健康研究II。此外，我们将评估端粒长度与端粒相关基因中的遗传变异和在黑色素瘤风险上燃烧/晒黑的趋势之间的相互作用。该应用程序将利用嵌套在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，高后续率和大型样本量。我们的研究还将利用先前确认的黑色素瘤病例，储存的血液和DNA样本，以及先前收集的有关宿主风险因素的信息。迄今为止，没有人评估端粒相关基因的端粒长度或遗传变异如何影响黑色素瘤的风险。在这项研究中，我们将检查端粒较短的女性黑色素瘤的风险是否更高，并且受到与端粒稳定性和维持相关的基因变异的影响。在诊断前收集的外周血白细胞和黑色素瘤风险中建立端粒长度之间的关系至关重要。它将为以下假设提供佐证，即与衰老有关的生物学过程是黑色素瘤风险的重要决定因素，并且可以提供一种用于评估黑色素瘤风险评估的一部分的测定。这项研究将有助于科学依据，以确定黑色素瘤高风险的人并提供个性化的风险管理策略。项目叙述：我们提出了对端粒长度的前瞻性评估以及与皮肤恶性黑色素瘤风险有关的端粒相关基因中的遗传变异。在诊断前收集的外周血白细胞和黑色素瘤风险中建立端粒长度之间的关系至关重要。它将为以下假设提供佐证，即与衰老有关的生物学过程是黑色素瘤风险的重要决定因素，并且可以提供一种用于评估黑色素瘤风险评估的一部分的测定。这项研究将有助于科学依据，以确定黑色素瘤高风险的人并提供个性化的风险管理策略。