Does Dietary Antioxidant Predict Aggressiveness of Prostate Cancer?

描述(由申请人提供)：相当多的证据表明，氧化应激对前列腺癌(PCa)的病因、发病机制和侵袭性有贡献。因此，膳食抗氧化剂被认为是防止前列腺癌发生的重要防御剂，它可以灭活活氧物质，保护机体免受氧化损伤。然而，在考虑了饮食和补充剂摄入量的流行病学研究中，抗氧化剂和PCA之间的联系并没有得到一致的证明。这种不一致的部分原因可能是未能解释人类饮食中抗氧化剂的主要来源，这些抗氧化剂来自许多不同的化学形式，并扰乱了这种联系。膳食总抗氧化能力(TAC)是一个新的概念，它使人们能够估计膳食抗氧化剂对氧化应激的保护作用的总和。膳食TAC估算是否正确反映体内抗氧化剂状态 氧化应激取决于饮食摄入量数据的完整性和有效性，其中包括准确的食物成分数据。我们最近的研究表明，高加索美国人(CA)的膳食TAC水平高于非裔美国人(AA)。根据2003-2007年美国癌症统计，AA的前列腺癌发病率比CA高50%，而AA的死亡率高150%。提出的解释这种差异的因素包括PCa筛查的种族差异、获得护理或寻求护理的行为，以及影响PCa生物学和侵袭性的病因和致病因素。PCA攻击性的种族差异可能部分归因于抗氧化剂摄入量的种族差异。然而，关于PCA侵袭性的营养调节方面的信息有限。因此，这项拟议研究的目标是确定饮食TAC预测PCA侵袭性的程度。中心假设是，验证一种新的TAC工具将能够预测由氧化应激介导的前列腺癌的风险。我们的工作假设是，PCA攻击性的种族差异在一定程度上是抗氧化剂摄入量的种族差异的结果。为了检验整个假设，我们的具体目标是：1)确定饮食TAC对新诊断的PCa侵袭性的影响；2)确定PCa患者的饮食TAC水平是否与血浆、尿液和PCa组织样本中的抗氧化剂氧化还原状态相关；以及3)利用北卡罗来纳州-路易斯安那州前列腺癌计划招募的新诊断PCa患者的数据，评估导致PCa患者饮食TAC存在种族差异的主要饮食、社会人口和生活方式因素。该项目将提供关于饮食TAC作为一种可改变的生活方式因素在被诊断为前列腺癌的男性中的重要信息，以及它在种族方面的差异程度。确定饮食对PCA攻击性的影响将表明生活方式行为因素在PCA结果中的重要性。此外，确定饮食行为的种族差异可能会提供信息，可用于开发适当的干预措施，以降低致命性前列腺癌的风险，减少前列腺癌死亡率的种族差异。

DESCRIPTION (provided by applicant): Considerable evidence suggests that oxidative stress contributes to the etiology, pathogenesis, and aggressiveness of prostate cancer (PCa). Consequently dietary antioxidants, which inactivate reactive oxygen species and provide protection from oxidative damage, are considered important preventive agents against the development of PCa. However, the association between antioxidants and PCa has not been demonstrated consistently across epidemiological studies that took into account both dietary and supplement intake. The inconsistencies may result in part from failure to account for major sources of antioxidants in human diets that derive from many different chemical forms and confound this association. Dietary total antioxidant capacity (TAC) is a new concept that enables one to estimate the sum of protective properties of dietary antioxidants against oxidative stress. Whether or not dietary TAC estimates correctly reflect in vivo antioxidant status and oxidative stress depends on the completeness and validity of dietary intake data that include accurate food composition data. Our recent studies indicate that dietary TAC levels of Caucasian Americans (CA) are higher than those of African Americans (AA). According to the U.S. Cancer Statistics for 2003-2007, the incidence rates of PCa are 50% higher for AA than CA, while mortality rates are 150% higher for AA. Factors proposed to explain this disparity include racial differences in PCa screening, access to care or care seeking behaviors, and etiologic and pathogenetic factors that influence PCa biology and aggressiveness. The racial disparity in PCa aggressiveness may be in part attributed to racial differences in antioxidant intake. However, limited information is available on the nutritional modulation of PCa aggressiveness. Thus, the objective of the proposed study is to determine the extent to which dietary TAC predicts PCa aggressiveness. The central hypothesis is that validation of a novel TAC tool will enable prediction of the risks of PCa mediated by oxidative stress. Our working hypothesis is that racial differences in PCa aggressiveness are in part the result of racial differences in antioxidant intake. To test the overall hypothesis, our specific aims are to: 1) determine the impact of dietary TAC on aggressiveness of newly diagnosed PCa; 2) determine whether dietary TAC level of PCa patients is associated with antioxidant-redox status in plasma, urinary, and PCa tissue samples; and 3) evaluate major dietary, sociodemographic, and lifestyle factors contributing to racial differences in dietary TAC of PCa patients by utilizing data on newl diagnosed PCa patients recruited through North Carolina-Louisiana Prostate Cancer Project. This project will provide important information on dietary TAC as a modifiable lifestyle factor among men diagnosed with PCa, and the extent to which it differs by race. Identification of dietary effects on PCa aggressiveness would suggest the importance of lifestyle behavioral factors in PCa outcome. Furthermore, the determination of racial differences in dietary behaviors may provide information that could be used to develop appropriate interventions to lower the risk of fatal PCa and reduce racial disparities in PCa mortality.