Non-Steroidal Anti-Inflammatory Drugs and Melanoma -- A Pooling Project

描述(由申请人提供)：在过去的70年里，美国的黑色素瘤发病率增加了15倍。尽管针对黑色素瘤的主要风险因素--阳光暴晒进行了预防努力，但这种疾病的死亡率仍在继续上升。因此，其他方法，如化学预防，已成为研究领域。一类有希望的药物，非类固醇抗炎药物(NSAIDs)，已经在细胞系和小鼠模型中证明了对黑色素瘤的保护作用。我们最近在人类中进行了一项病例对照研究，发现服用非阿司匹林非类固醇抗炎药的受试者与不服用这些药物的人相比，患黑色素瘤的风险降低了40%。基于这些结果，我们提出了一项研究，致力于调查我们的假设，即定期使用非类固醇抗炎药对黑色素瘤具有化学保护作用。我们将通过汇集护士健康研究和卫生专业人员后续研究的数据来评估这一假设，以解决三个具体目标：(1)确认我们初步发现非类固醇抗炎药的使用与侵袭性黑色素瘤风险之间存在负相关关系；(2)确定非类固醇抗炎药对原位黑色素瘤风险的影响；以及(3)评估非类固醇抗炎药对黑色素瘤侵袭的影响，以肿瘤Breslow深度和生长阶段为衡量标准。通过汇集这些研究，可以确定对男性和女性的影响，并增加对影响的更准确估计的力量。通过我们对这些研究的现有数据的分析，我们希望找到一种用于临床化学预防试验的试剂。由于服用非甾体类抗炎药的人数众多，黑色素瘤的发病率不断上升，我们相信检测到一种效应将对公众健康做出重大贡献。这项研究建议调查定期使用非类固醇抗炎药(NSAIDs)是否可以保护个人免受黑色素瘤的侵袭。这个问题将使用护士健康研究和健康专业人员后续研究的数据来解决，这两大健康专业人员群体提供了长达24年的健康信息。由于服用非甾体类抗炎药的人数众多，黑色素瘤的发病率不断上升，我们相信检测到一种效应将对公众健康做出重大贡献。

DESCRIPTION (provided by applicant): Melanoma incidence in the United States has increased 15-fold over the last 70 years. Despite prevention efforts targeting sun exposure, the major risk factor for melanoma, the mortality from this disease continues to rise. Therefore, other approaches such as chemoprevention have emerged as areas of investigation. One promising class of medications, non-steroidal anti-inflammatory drugs (NSAIDs), has demonstrated protective effects against melanoma in cell lines and mouse models. We have recently conducted a case-control study in humans that found that subjects taking non-aspirin NSAIDs had a 40% decreased risk of melanoma compared to those who did not take these medications. Based on these results, we propose a study dedicated to investigating our hypothesis that regular use of NSAIDs has a chemoprotective effect against melanoma. We will evaluate this hypothesis by pooling data from the Nurses Health Study and the Health Professionals Follow-up Study to address three specific aims: (1) To confirm our preliminary finding of an inverse relationship between the use of NSAIDs and risk of invasive melanoma; (2) To determine the effects of NSAIDs on risk of melanoma in situ, and (3) To assess the influence of NSAIDs on melanoma invasion, as measured by tumor Breslow depth and growth phase. By pooling these studies, effects can be determined in both men and women, and power is increased for more precise estimates of effect. Through our analysis of existing data from these studies, we hope to identify an agent for clinical chemoprevention trials. Due to the large numbers of individuals taking NSAIDs and the increasing incidence of melanoma, we believe that the detection of an effect will make a significant contribution to the public health. This study proposes to investigate whether regular use of non-steroidal anti-inflammatory drugs (NSAIDs) may protect individuals against melanoma. This question will be addressed using data from the Nurses Health Study and the Health Professionals Follow-up Study, two large groups of health professionals who have provided information about their health for up to 24 years. Due to the large numbers of individuals taking NSAIDs and the increasing incidence of melanoma, we believe that the detection of an effect will make a significant contribution to the public health.