Prospective study of telomere length and melanoma risk

描述（由申请人提供）： 摘要：端粒长度与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年龄相关疾病（如癌症）风险的潜在生物标志物。端粒长度部分由遗传因素决定。除了造成DNA损伤外，UVB照射还会缩短端粒。在皮肤组织中，端粒破坏引发多种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）的风险。我们将纳入586例黑色素瘤事件病例和586例匹配对照，这些病例在诊断前提供了来自三个大型特征良好的队列（妇女健康倡议观察性研究、护士健康研究和护士健康研究II）的血液样本。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黑色素瘤风险的烧伤/晒黑倾向。本申请将利用现有特征良好的队列中嵌套的研究机会，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认的黑色素瘤病例、储存的血液和DNA样本以及先前收集的关于宿主风险因素的信息。到目前为止，还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的风险。在这项研究中，我们将研究端粒较短的女性患黑色素瘤的风险是否更高，以及端粒稳定性和维持相关基因变异的影响。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将是重要的，原因有几个。这将为与衰老相关的生物学过程是黑色素瘤风险的重要决定因素这一假设提供确证，并可能提供一种用于黑色素瘤风险评估的测定方法。这项研究将有助于确定黑色素瘤高风险个体的科学基础，并提供个性化的风险管理策略。项目叙述：我们提出了一个前瞻性的评估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的风险。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将是重要的，原因有几个。这将为与衰老相关的生物学过程是黑色素瘤风险的重要决定因素这一假设提供确证，并可能提供一种用于黑色素瘤风险评估的测定方法。这项研究将有助于确定黑色素瘤高风险个体的科学基础，并提供个性化的风险管理策略。

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.