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

描述(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，通常对传统疗法无效。因此，关键是要确定可用于预防工作的可改变因素，以降低发生这种疾病的风险。饮食、体力活动和肥胖被认为可能影响患胰腺癌的风险，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，但除了极少数例外，很少有证据表明它们的好处或风险。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，使用先前从大量补充剂使用者中收集的数据。主要的具体目标是调查在截至基线的10年中补充营养素摄入与抗炎(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)与胰腺癌发病率的关系。次要目标是检查特定的、不太常见的维生素、矿物质、植物和其他补充剂(如叶酸、铁、银杏叶)和非类固醇抗炎药(NSAIDs)的摄入量与胰腺癌发病率的关系；以及基线和18、30、45岁时的体力活动和身体质量指数水平与胰腺癌发病率的关系。方法2000-2002年间，来自华盛顿州西部的77,738名年龄在50-76岁的男性和女性完成了一份基线问卷，该问卷收集了过去10年中38种补充剂的使用情况、饮食、体力活动(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。补充剂使用者是招募对象；因此，队列成员的补充剂使用率高且持续时间长：79%的人曾经使用补充剂，66%的人使用多种维生素，46%的人使用单独的维生素C，47%的人使用单独的维生素E，通常在过去10年中的5-8年。在胰腺癌队列之后，通过与华盛顿州西部SEER癌症登记联系，通过与华盛顿州死亡文件联系死亡，通过与国家地址更改系统联系，从SEER集水区向外迁移。这项提案寻求资金，以进行针对具体目标的分析。我们希望在平均8.3年的随访期后确定215例胰腺癌病例。主要暴露于感兴趣的营养素(单一补充剂和多种维生素)的前10年的平均每日摄入量，所有分析都将针对饮食和其他潜在的混杂因素和效果调节剂进行调整。意义这项研究的结果将是第一批检验膳食补充剂的使用以及体力活动和肥胖与胰腺癌风险之间的关联的研究之一。胰腺癌是一种死亡率很高的疾病，几乎没有已知的可改变的风险因素。我们将使用唯一一项专门关注膳食补充剂与癌症风险的病因学关系的队列研究的数据，该研究仔细地衡量了补充剂的使用和混杂因素。重要的是，鉴于膳食补充剂在美国的使用率很高，我们的发现将对公众健康产生重要影响，无论我们是否发现补充剂对胰腺癌风险具有保护作用、增加风险或没有影响。公共卫生相关性：胰腺癌是一种高度致命的疾病，几乎没有已知的可改变的危险因素。有研究表明，饮食、体力活动和肥胖可能会影响胰腺癌的发生，但结果并不一致。此外，许多美国人使用膳食补充剂(维生素、矿物质和草药)，但对其潜在的益处和风险知之甚少。这项拟议研究的目标是检查各种膳食补充剂以及基线和18、30、45岁年龄段的体力活动和身体质量指数水平与胰腺癌发病率的关系。为了实现这些目标，我们将在华盛顿州西部50-76岁(基线)的一大群男性和女性(n=77,738)中进行二级数据分析。队列成员完成了一份详细的基线问卷，涵盖了过去10年的补充剂使用、饮食、体力活动、人体测量学、健康史和癌症风险因素。通过与华盛顿州西部SEER癌症登记中心的联系，平均随访8.3年后，预计将确定215例胰腺癌病例。这项拟议的项目将提供有关膳食补充剂的使用以及体力活动和体重指数是否与胰腺癌发病率相关的有价值的信息，并将对数百万服用补充剂的美国成年人有用，无论是否发现特定补充剂的保护作用、无影响或风险增加。

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. PUBLIC HEALTH RELEVANCE: Pancreatic cancer is a highly fatal disease for which there are few known modifiable risk factors. It has been suggested that diet, physical activity, and obesity may impact pancreatic cancer development, but results are inconsistent. Also, many Americans use dietary (vitamin, mineral, and herbal) supplements with limited knowledge regarding their potential benefits and risks. The goal of this proposed study is to examine associations of various dietary supplements, as well as physical activity and body mass index levels at baseline and ages 18, 30, and 45 years, with pancreatic cancer incidence. To accomplish these aims, we would conduct secondary data analyses within a large cohort of men and women (n=77,738), 50-76 years (at baseline) in western Washington state. Cohort members completed a detailed baseline questionnaire covering supplement use over the past 10 years, diet, physical activity, anthropometrics, health history, and cancer risk factors. An expected 215 pancreatic cancer cases would be identified after a mean follow-up of 8.3 years by linkage to the western Washington SEER cancer registry. This proposed project would provide valuable information regarding whether use of dietary supplements, as well as physical activity and body mass index are associated with pancreatic cancer incidence, and would be useful for the millions of American adults who take supplements, regardless of whether protective effects, no effects, or increased risks for specific supplements are found.