Defining critical aspects of environmental ultraviolet exposure in melanogenesis

描述（由申请人提供）：这一竞争性修订旨在大大提高我们从自我报告中回顾性估计终身和年龄特异性太阳紫外线（UV）暴露的能力，并增强我们为父母奖开发并正在使用的新型紫外线暴露度量标准。除了加强父母奖的科学方法外，这项额外的方法工作将广泛适用于自我们的父母奖开始以来由调查小组的合作者发起的关于紫外线照射和疾病结果的许多其他研究。我们之前开发了一种方法来推算一生和年龄特异性紫外线暴露。我们现在有机会验证紫外线测量与实时紫外线剂量法的对比，并利用这些信息更好地测量回顾性紫外线照射，特别是与黑色素瘤相关的极端和间歇性照射，但目前的方法无法很好地测量。在本研究中，我们的目标是描述估算紫外线照射与个人实时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（并非所有人都会因为处于相同的地理位置而接受相同的紫外线照射）。对于黑色素瘤来说，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衡量的，比如在阳光下度假、日光浴或短期周末暴露。这些自我报告几乎肯定会对间歇性暴露估计进行错误分类，而且不清楚哪种测量方法最能代表间歇性紫外线暴露。我们的紫外线测量测量的是总紫外线，但对于黑色素瘤，我们还想知道总紫外线暴露的组成部分，可归因于特定波长（粗略地说，UVA和UVB）。我们已经开发了剂量计，以便将波长特定的紫外线测量与自我报告的阳光照射行为联系起来。我们将在父母奖研究人群中通过剂量学测量紫外线，并使用这些数据来模拟自我报告的测量、我们的估算紫外线度量（两者也可用于回顾性数据）和实时紫外线暴露（特别是间歇性和极端暴露，以及UVA和UVB波长的分别贡献）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的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。这一竞争性修订申请符合ARRA资助的所有标准，既加快了直接用于父母补助金和相关科学的科学研究的节奏，也促进了创造/保留就业机会，这是经济刺激法案的主要重点。

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.