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

基本信息

批准号：
7372994
负责人：
MYLES G COCKBURN
金额：
$ 36.68万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-01-01 至 2012-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7372994
关键词：
21 year old Address Adult Age Behavior Behavioral Genetics Burn injury California Cancer Etiology Case-Control Studies Childhood Chronic Complement DNA Damage Data Dermal Development Diagnosis Doctor of Philosophy Dose Epidemiologic Studies Epidemiology Etiology Exposure to Future Genetic Genetic Predisposition to Disease Genotype Geographic Information Systems Incidence Investigation Lead Malignant Neoplasms Measurement Measures Melanocytic nevus Melanogenesis Methods Modeling Mole the mammal Monozygotic twins Nested Case-Control Study Nevus Normal tissue morphology Paraffin Embedding Pathway interactions Patient Self-Report Pattern Pigmentation physiologic function Play Population Primary Prevention Principal Investigator Range Recording of previous events Reporting Research Retrospective Studies Risk Risk Estimate Risk Factors Role Sampling Skin Skin Cancer Skin Carcinoma Solar Energy Specimen Staining method Stains Sun Exposure Sunburn Surface Time Tumor Markers Twin Multiple Birth Ultraviolet B Radiation Ultraviolet Rays Variant Viola Work absorption age effect base cohort gene environment interaction improved male melanoma member novel programs research study response success tumor ultraviolet

项目摘要

DESCRIPTION (provided by applicant): Sun exposure has been consistently implicated in the development of non-melanoma skin cancers, but its role in melanoma etiology remains controversial, and is complicated by poorly understood genetic and behavioral factors. Melanoma incidence continues to increase (it is now the 4th most common cancer among males in California). Efforts to reduce melanoma incidence through sun exposure avoidance have had limited success, underscoring our lack of understanding of the true mechanisms of melanogenesis. Melanoma epidemiology is based on retrospective studies: recall bias probably explains associations between sunburn (almost always self-reported) and melanoma. Moreover, sun burn represents only excessive exposure to solar radiation, while sun-induced DNA damage potentially occurs across all levels of intensity: there is no accepted method for directly measuring sun exposure in epidemiological studies. In order to better understand the etiology of melanoma (particularly the role of sun exposure), valid methods of assessing both current and historical sun exposure are needed. While genetic factors probably play some role in melanogenesis, no study has yet managed to distinguish genetic from sun exposure-related risks. We will address both these issues in a case-control study of identical twins (nested in an established population-based cohort of 52,000 twins in California) assessing the role of sun exposure in melanoma etiology in the absence of genetic effects. Historical sun exposure will be assessed by combining residential history with novel fine-layer interpolated solar radiation level using GIS: we have already shown this method significantly reduces misclassification and recall bias. We will measure the actual impact of solar radiation on the skin, measuring UV- induced epidermal damage in tumor specimens noting differences in risk with varying UV intensity and wavelength. These results have the potential to improve primary prevention of melanoma and other skin cancers, and to direct the research team's future work on gene-environment interactions relevant to melanogenesis. We will measure the actual impact of solar radiation on the skin, measuring ultra-violet (UV)-induced epidermal damage in tumor specimens noting differences in risk with varying UV intensity and wavelength, and estimating the risk of melanoma with lifetime and age- specific exposures to specific wavelengths of UV. These results have the potential to improve primary prevention of melanoma and other skin cancers by indicating the appropriate means of avoiding harmful UV exposure, and to direct the research team's future work on gene-environment interactions relevant to melanogenesis.

描述（由申请人提供）：暴露在非黑色素瘤皮肤癌的发展中一直与之相关，但其在黑色素瘤病因中的作用仍然存在争议，并且由于遗传和行为因素而言，它的理解不足。黑色素瘤的发病率继续增加（现在是加利福尼亚男性中第四大癌症）。通过避免太阳暴露来减少黑色素瘤发病率的努力取得了有限的成功，强调了我们对黑色素生成的真实机制的缺乏。黑色素瘤流行病学基于回顾性研究：回忆偏见可能解释了晒伤（几乎总是自我报告）和黑色素瘤之间的关联。此外，太阳燃烧仅代表过度暴露于太阳辐射，而太阳引起的DNA损伤可能发生在所有级别的强度上：在流行病学研究中没有可接受的方法直接测量日晒。为了更好地了解黑色素瘤的病因（尤其是太阳暴露的作用），需要评估当前和历史阳光的有效方法。尽管遗传因素可能在黑色素发生中起作用，但尚无研究将遗传与与日光暴露有关的风险区分开。我们将在一项对同卵双胞胎的病例对照研究中解决这两个问题（嵌套在加利福尼亚州的52,000个双胞胎的基于人群的同类中），该研究在没有遗传作用的情况下评估了日晒在黑色素瘤病因中的作用。使用GIS将住宅历史与新颖的高层插值太阳辐射水平相结合来评估历史阳光的暴露：我们已经证明了这种方法可大大减少错误分类和回忆偏见。我们将测量太阳辐射对皮肤的实际影响，测量肿瘤标本中紫外线诱导的表皮损伤，这些肿瘤标本指出风险差异，紫外线强度和波长变化。这些结果有可能改善黑色素瘤和其他皮肤癌的一级预防，并指导研究团队对与黑色素生成有关的基因环境相互作用的未来工作。我们将衡量太阳辐射对皮肤的实际影响，测量肿瘤标本中超紫（UV）诱导的表皮损伤，这些肿瘤标本中指出风险差异的紫外线强度和波长的风险差异，并估算了与UV的特定波长有关寿命和年龄的外观和年龄的外观风险。这些结果有可能通过指示避免有害紫外线暴露的适当方法，并指导研究团队对基因 - 环境相互作用的未来工作，从而改善对黑色素瘤和其他皮肤癌的一级预防。