Defining critical aspects of environmental ultraviolet exposure in melanogenesis

定义环境紫外线暴露在黑素生成中的关键方面

• 批准号: 7818220
• 负责人: MYLES G COCKBURN
• 金额: $ 48.1万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-20 至 2010-09-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7818220
• 关键词: Affect; Age; Award; Bathing; Behavior; Data; Devices; Disease; Disease Outcome; Eating; Exposure to; Frequencies; Funding; Genetic Predisposition to Disease; Geographic Locations; Incidence; Individual; Location; Measures; Mediating; Melanogenesis; Methods; Metric; Modeling; Occupational; Occupations; Parents; Patient Self-Report; Pattern; Population; Population Study; Primary Prevention; Recruitment Activity; Research; Retrospective Studies; Risk; Role; Science; Seasons; Solar Energy; Stimulus; Sun Exposure; The Sun; Time; Ultraviolet B Radiation; Validation; Variant; Weight; Work; base; behavior change; dosimetry; experience; meetings; melanoma; novel; parent grant; prospective; public health relevance; residence; self reported behavior; success; ultraviolet; volunteer

DESCRIPTION (provided by applicant): This Competitive Revision aims to greatly enhance our ability to estimate lifetime and age-specific solar ultraviolet (UV) exposures obtained retrospectively from self-report and enhance the novel UV exposure metric that we developed for, and are using in, the Parent Award. As well as enhancing the scientific approach of the Parent Award, this additional methodological work will have wide applicability to a number of other studies of UV exposure and disease outcome that have been initiated since our Parent Award began, by collaborators of the investigative team. We previously developed a method of imputing lifetime and age-specific UV exposure. We now have an opportunity to validate that UV metric against real-time UV dosimetry, and use that information to better measure retrospective UV exposure, especially extreme and intermittent exposures that are relevant to melanoma but not well measured by current methods. In the proposed study, we aim to characterize the relationship between imputed UV exposure and real-time personal UV exposure: that relationship is certainly mediated by sun exposure behavior (not all people will receive the same UV exposure just because they are in the same geographical location). For melanoma, a critical issue is the impact of past intermittent exposure on disease. Currently, intermittent UV exposure is measured by self-report of activities such as vacations in the sun, sun bathing, or short term weekend exposures. These self-reports almost certainly misclassify intermittent exposure estimates, and it is unclear which measure best represents intermittent UV exposure. Our UV metric measures total UV, but for melanoma we also want to know the component of total UV exposure that is attributable to specific wavelengths (crudely, UVA and UVB). Our dosimeters have been developed in order to correlate wavelength-specific UV measures with self-reported sun exposure behavior. We will measure UV from dosimetry in the Parent Award study population, and use those data to model the relationship between self-reported measures, our imputed UV metric (both of which are available for retrospective data also) and real time UV exposure (especially intermittent and extreme exposures, and the contribution of UVA and UVB wavelengths separately). The proposed study will further accelerate our progress towards the central theme of reducing exposure assessment error in order to determine the true effects of UV exposure on melanoma. This Competitive Revision application meets ALL of the criteria for funding under the ARRA, both for accelerating the tempo of scientific research directly for the Parent Grant and for associated science, and for job creation/retention that is the primary focus of the Stimulus Bill. PUBLIC HEALTH RELEVANCE: Melanoma incidence is increasing steadily in most populations worldwide, and primary prevention efforts (largely based on avoiding sun exposure around midday) have had limited success. Our Parent Award aims to better characterize the role of varying wavelengths of solar ultraviolet (UV) on melanoma, in the absence of the muddying effect of genetic susceptibility, and provide the 'cleanest' picture of how to achieve primary prevention through behavior change. The proposed study enhances those aims by relating imputed UV exposures (based on self-report) to real time UV exposure from dosimetry, using devices that also measure wavelength-specific UV. Those dosimetry data will be modeled against self report and imputed UV data to determine the best way to measure variability in past UV exposures that is relevant to melanoma, focusing specifically on intermittent and extreme exposures that current methods almost certainly fail to accurately capture.

描述（由申请人提供）：本次竞争性修订旨在大大增强我们根据自我报告回顾性地估计寿命和特定年龄太阳紫外线 (UV) 暴露的能力，并增强我们为家长奖开发并正在使用的新型紫外线暴露指标。除了增强“家长奖”的科学方法之外，这项额外的方法学工作还将广泛适用于自“家长奖”开始以来由调查团队的合作者发起的许多其他关于紫外线暴露和疾病结果的研究。我们之前开发了一种估算寿命和特定年龄紫外线暴露的方法。我们现在有机会根据实时紫外线剂量测定来验证紫外线指标，并使用该信息更好地测量回顾性紫外线暴露，特别是与黑色素瘤相关但目前方法无法很好测量的极端和间歇性暴露。在拟议的研究中，我们的目标是描述估算的紫外线照射与实时个人紫外线照射之间的关系：这种关系肯定是由阳光照射行为介导的（并非所有人都会仅仅因为处于相同的地理位置而受到相同的紫外线照射）。对于黑色素瘤，一个关键问题是过去间歇性接触对疾病的影响。目前，间歇性紫外线暴露是通过自我报告的活动来测量的，例如在阳光下度假、日光浴或短期周末暴露。这些自我报告几乎肯定对间歇性暴露估计进行了错误分类，并且尚不清楚哪种措施最能代表间歇性紫外线暴露。我们的紫外线指标测量的是总紫外线，但对于黑色素瘤，我们还想知道特定波长（粗略地说，UVA 和 UVB）导致的总紫外线暴露量的组成部分。我们开发的剂量计是为了将特定波长的紫外线测量值与自我报告的阳光照射行为相关联。我们将通过家长奖研究人群的剂量测定来测量紫外线，并使用这些数据来模拟自我报告的测量值、我们的推算紫外线指标（两者也可用于回顾性数据）和实时紫外线暴露（尤其是间歇性和极端暴露，以及 UVA 和 UVB 波长分别的贡献）之间的关系。拟议的研究将进一步加速我们在减少暴露评估误差这一中心主题方面的进展，以确定紫外线暴露对黑色素瘤的真正影响。该竞争性修订申请符合 ARRA 资助的所有标准，既可以直接加快家长补助金和相关科学的科学研究速度，也可以创造/保留就业机会，这是刺激法案的主要重点。 公共卫生相关性：全球大多数人群中黑色素瘤的发病率正在稳步上升，初级预防工作（主要是避免中午晒太阳）的成功有限。我们的家长奖旨在在没有遗传易感性的混乱影响的情况下，更好地描述不同波长的太阳紫外线 (UV) 对黑色素瘤的作用，并提供如何通过行为改变实现一级预防的“最清晰”的画面。拟议的研究通过使用同时测量特定波长紫外线的设备，将估算的紫外线暴露（基于自我报告）与剂量测定中的实时紫外线暴露联系起来，从而增强了这些目标。这些剂量测定数据将根据自我报告和估算的紫外线数据进行建模，以确定测量与黑色素瘤相关的过去紫外线暴露变化的最佳方法，特别关注当前方法几乎肯定无法准确捕获的间歇性和极端暴露。