Dietary supplement use, physical activity, body mass index, and pancreatic cancer

描述（由申请人提供）：胰腺癌是美国癌症死亡的第四大常见原因，预后非常差，通常对常规治疗无反应。因此，确定可用于预防工作的可改变因素以降低患此病的风险至关重要。饮食、体育活动和肥胖被认为可能影响胰腺癌的风险，但结果并不一致。此外，数以百万计的美国人使用膳食补充剂（维生素、矿物质和草药）来预防癌症和其他疾病，但除了少数例外，很少有证据表明它们的益处或风险。本研究的目的是研究各种膳食补充剂与胰腺癌发病率的关系，使用先前从一项大型队列研究中收集的数据，该研究中有高比例的补充剂使用者。主要的具体目的是调查在基线结束的10年期间补充摄入具有抗炎（维生素E、硒和omega-3脂肪酸）和抗氧化特性（维生素C、维生素E、β -胡萝卜素、番茄红素和硒）的营养素与胰腺癌发病率之间的关系。次要目的是检查特定的、不常见的维生素、矿物质、植物和其他补充剂（如叶酸、铁、银杏叶）和非甾体抗炎药（NSAIDs）的摄入量之间的关系；以及18岁，30岁和45岁胰腺癌患者的身体活动和体重指数水平。方法2000-2002年间，来自华盛顿州西部的77,738名年龄在50-76岁之间的男性和女性完成了一份基线问卷，该问卷收集了过去10年38种补充剂的使用情况、饮食、体育活动（使用有效问卷）、人体测量学、健康史和癌症风险因素的详细信息。补充用户的招募有针对性；因此，队列成员服用补充剂的时间既高又长：79%的人曾经服用过补充剂，66%的人服用复合维生素，46%的人服用单一维生素C， 47%的人服用单一维生素E，通常在过去10年的5-8年。该队列通过与西华盛顿SEER癌症登记处的联系来跟踪胰腺癌，通过与华盛顿州死亡档案的联系来跟踪死亡，并通过与国家地址变更系统的联系来跟踪从SEER集水区向外迁移的队列。这项建议寻求资金进行针对具体目标的分析。我们期望在平均8.3年的随访后确定215例胰腺癌病例。主要暴露量是研究对象在过去10年里每天的平均摄入量（单一补充剂加上多种维生素），所有的分析都将根据饮食和其他潜在的混杂因素和影响调节因素进行调整。这项研究的结果将是第一个研究膳食补充剂使用、体育活动和肥胖与胰腺癌风险之间关系的研究之一，胰腺癌是一种死亡率高、已知可改变的风险因素很少的疾病。我们将使用唯一一项队列研究的数据，该研究特别关注膳食补充剂与癌症风险的病因学关系，仔细测量了补充剂的使用情况和混杂因素。重要的是，鉴于膳食补充剂在美国的高流行率，我们的研究结果将具有重要的公共卫生意义，无论我们是否发现补充剂对胰腺癌风险的保护作用、增加风险或没有影响。

DESCRIPTION (provided by applicant): Pancreatic cancer is the fourth most common cause of cancer deaths in the United States (U.S.), has a very poor prognosis, and is generally unresponsive to conventional therapies. Therefore, it is critical to identify modifiable factors that can be used in prevention efforts to reduce risk for developing this disease. Diet, physical activity, and obesity have been postulated to potentially influence pancreatic cancer risk, but results are inconsistent. Also, millions of Americans use dietary (vitamin, mineral, and herbal) supplements to prevent cancer and other diseases, but with few exceptions, there is sparse evidence for either their benefits or risks. Specific Aims The goal of this study is to examine associations of various dietary supplements with pancreatic cancer incidence, using previously collected data from a large cohort study with a high proportion of supplement users. The primary specific aims are to investigate associations of supplemental intakes of nutrients with anti-inflammatory (vitamin E, selenium, and omega-3 fatty acids) and antioxidant properties (vitamin C, vitamin E, beta-carotene, lycopene, and selenium) over the 10-year period ending at baseline with the incidence of pancreatic cancer. Secondary aims are to examine associations of intakes of specific, less common vitamin, mineral, botanical, and other supplements (e.g., folate, iron, gingko biloba) and non- steroidal anti-inflammatory drugs (NSAIDs); as well as physical activity and body mass index levels at baseline and ages 18, 30, and 45 years with pancreatic cancer incidence. Methods Between 2000-2002, 77,738 men and women, aged 50-76 from western Washington State completed a baseline questionnaire that captured detailed information on use of 38 supplements over the previous 10 years, diet, physical activity (using a validated questionnaire), anthropometrics, health history, and cancer risk factors. Supplement users were targeted in recruitment; therefore, supplement use by cohort members is both high and of long duration: 79% were ever users of a supplement, and 66% used multivitamins,46% used individual vitamin C, and 47% used individual vitamin E, typically for 5-8 of the previous 10years. The cohort is being followed for pancreatic cancers by linkage to the western Washington SEER cancer registry, deaths by linkage to the Washington State death file, and out-migration from the SEER catchment area by linkage to the National Change of Address system. This proposal seeks funds to conduct analyses addressing the specific aims. We expect to identify 215 pancreatic cancer cases after a mean follow-up of 8.3 years. The primary exposure would be average intake per day over the previous 10 years of the nutrient of interest (single supplements plus multivitamins), and all analyses will be adjusted for diet and other potential confounders and effect modifiers. Significance The results of this study will be one of the first to examine associations of dietary supplement use, as well as physical activity and obesity, with risk for pancreatic cancer, a disease with a high fatality rate and few known modifiable risk factors. We would use data from the only cohort study specifically focused on the etiologic relationships of dietary supplements with cancer risk which carefully measured supplement use and confounding factors. Importantly, given the high prevalence of dietary supplement use in the U.S., our findings will have important public health implications regardless of whether we find protective effects, increased risks, or no effects of supplements on pancreatic cancer risk.