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。尽管预防措施的目标是阳光照射，这是黑色素瘤的主要危险因素，但这种疾病的死亡率仍在继续上升。因此，化学预防等其他方法已成为研究领域。一种很有前途的药物，非甾体抗炎药（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类非甾体抗炎药的受试者患黑色素瘤的风险比不服用这些药物的受试者降低了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，即定期使用非甾体抗炎药对黑色素瘤有化学保护作用。我们将通过汇集护士健康研究和卫生专业人员随访研究的数据来评估这一假设，以实现三个具体目标：(1)证实我们的初步发现，即非甾体抗炎药的使用与侵袭性黑色素瘤的风险之间存在负相关关系；(2)确定非甾体抗炎药对原位黑色素瘤风险的影响；(3)通过肿瘤Breslow深度和生长阶段评估非甾体抗炎药对黑色素瘤侵袭的影响。通过汇集这些研究，可以确定男性和女性的影响，并且可以更精确地估计影响。通过我们对这些研究现有数据的分析，我们希望找到一种用于临床化学预防试验的药物。由于大量个体服用非甾体抗炎药和黑色素瘤发病率的增加，我们相信检测其效果将对公众健康做出重大贡献。本研究提出调查是否定期使用非甾体抗炎药（NSAIDs）可以保护个人免受黑色素瘤。这个问题将使用护士健康研究和卫生专业人员随访研究的数据来解决，这两大组卫生专业人员提供了长达24年的健康信息。由于大量个体服用非甾体抗炎药和黑色素瘤发病率的增加，我们相信检测其效果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.