Analgesic Use and Kidney Cancer

描述（由申请人提供）：肾癌是男性第七大恶性疾病，女性第九大恶性疾病，占所有癌症的4%。大多数肾癌是肾细胞癌（RCC），其余病例主要是肾盂癌。肾癌的发病率在美国和世界范围内一直在上升。然而，这种恶性肿瘤的病因在很大程度上是未知的。镇痛药是一组用于缓解疼痛的药物，包括对乙酰氨基酚和非甾体抗炎药（NSAID）。NSAID阿司匹林是美国最常用的药物之一，以其对心血管疾病和结直肠癌的保护作用而闻名。阿司匹林可以通过减少炎症、抑制环氧合酶-2、抑制细胞增殖和诱导癌细胞凋亡来减少肾癌。然而，可用的流行病学数据有限，止痛药使用和肾癌风险的前瞻性数据很少。此外，先前关于止痛药使用和肾癌风险的病例对照研究指出了正相关。事实上，一些止痛药如对乙酰氨基酚可能会导致肾功能下降和慢性肾脏疾病的风险增加，随后增加肾癌的风险。因此，考虑到阿司匹林和其他镇痛药的普及，从公共卫生的角度来看，澄清这种关联是必要的。在本申请中，我们将确定个体和总体镇痛药使用对肾癌风险的影响。我们假设使用阿司匹林和其他非甾体抗炎药与肾癌风险降低相关，但使用对乙酰氨基酚与肾癌风险升高相关。我们将使用两种不同的研究设计来评估这些假设：1）在男性和女性430例肾癌病例（350例RCC）的大型前瞻性研究中，2）在既往文献的荟萃分析中，包括病例对照和队列研究，超过5，600例肾癌病例。这两种研究设计将补充每种研究设计的优势。我们相信，这项拟议的工作将提供最好的数据镇痛剂的使用和肾癌的风险，并大大提高我们的理解镇痛剂在肾癌发生的作用。我们的研究结果将为这些关联的潜在生物学机制提供见解。由于阿司匹林和其他止痛药的普及，这项拟议中的工作具有重大的公共卫生意义。

DESCRIPTION (provided by applicant): Kidney cancer is the 7th leading malignant condition among men and the 9th among women, accounting for 4% of all cancers. The majority of kidney cancer is renal cell cancer (RCC), with the remainder of cases mostly renal pelvis cancer. The incidence of kidney cancer has been rising in the U.S. and worldwide. Nevertheless, the etiology of this malignancy is largely unexplored. Analgesics are a diverse group of drugs used to relieve pain, including acetaminophen and non-steroidal anti- inflammatory drugs (NSAIDs). The NSAID aspirin is one of the most commonly used drugs in the U.S. and is well-known for its protective effect against cardiovascular disease and colorectal cancer. Aspirin may reduce kidney cancer by reducing inflammation, inhibiting cycloxygenase-2, inhibiting cell proliferation, and inducing apoptosis of cancer cells. However, limited epidemiologic data are available, with few prospective data for analgesic use and kidney cancer risk. Furthermore, previous case-control studies on analgesic use and kidney cancer risk point toward a positive association. In fact, some analgesics such as acetaminophen may contribute to decline of renal function and elevated risk of chronic renal disease and, subsequently, to elevated risk of kidney cancer. Thus, given the popularity of aspirin and other analgesics, clarification of the association is necessary from a public health standpoint. In this application, we will determine the effects of individual and total analgesic use on the risk of kidney cancer. We hypothesize that use of aspirin and other NSAIDs is associated with a reduced risk of kidney cancer, but that use of acetaminophen is associated with an elevated risk of kidney cancer. We will evaluate these hypotheses using two different study designs; 1) in large prospective studies of male and female with 430 kidney cancer cases (350 RCC) and 2) in a meta-analysis of previous literature including both case-control and cohort studies with over 5,600 kidney cancer cases. These two study designs will complement the strength of each study design. We believe that this proposed work will provide the best available data on analgesic use and kidney cancer risk and substantially enhance our understanding of the role of analgesics in renal carcinogenesis. Our findings will provide insights into the biological mechanisms potentially underlying these associations. Because of the popularity of aspirin and other analgesics, this proposed work has substantial public health implications.