Analgesic Use and Kidney Cancer

描述（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。在美国和世界范围内，肾癌的发病率一直在上升。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（NSAIDs）。非甾体抗炎药阿司匹林是美国最常用的药物之一，因其对心血管疾病和结直肠癌的保护作用而闻名。阿司匹林可能通过减轻炎症、抑制环氧化酶-2、抑制细胞增殖、诱导癌细胞凋亡等途径降低肾癌。然而，流行病学数据有限，关于止痛药使用和肾癌风险的前瞻性数据也很少。此外，先前的病例对照研究表明，镇痛药的使用与肾癌风险呈正相关。事实上，一些镇痛药，如对乙酰氨基酚，可能导致肾功能下降，增加慢性肾脏疾病的风险，进而增加患肾癌的风险。因此，鉴于阿司匹林和其他镇痛药的普及，从公共卫生的角度澄清两者之间的联系是必要的。在本应用中，我们将确定单个和总镇痛药使用对肾癌风险的影响。我们假设阿司匹林和其他非甾体抗炎药的使用与肾癌风险的降低有关，但对乙酰氨基酚的使用与肾癌风险的升高有关。我们将使用两种不同的研究设计来评估这些假设；1)在430例肾癌（350例RCC）的男性和女性的大型前瞻性研究中，2)在既往文献的荟萃分析中，包括超过5600例肾癌病例的病例对照和队列研究。这两个研究设计将补充每个研究设计的优势。我们相信这项工作将为止痛剂的使用和肾癌风险提供最好的数据，并大大提高我们对止痛剂在肾癌发生中的作用的理解。我们的发现将为这些关联背后潜在的生物学机制提供见解。由于阿司匹林和其他镇痛药的普及，这项拟议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.