Does Dietary Antioxidant Predict Aggressiveness of Prostate Cancer?

描述（由申请人提供）：大量证据表明，氧化应激有助于前列腺癌（PCa）的病因、发病机制和侵袭性。因此，膳食抗氧化剂，其抑制活性氧簇并提供对氧化损伤的保护，被认为是预防PCa发展的重要预防剂。然而，抗氧化剂和PCa之间的关联在考虑饮食和补充剂摄入的流行病学研究中并没有得到一致的证明。这种不一致的部分原因可能是没有考虑到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，并混淆了这种联系。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特性的总和。膳食TAC估计值是否正确反映体内抗氧化状态 氧化应激取决于饮食摄入数据的完整性和有效性，包括准确的食物成分数据。我们最近的研究表明，饮食中的总抗氧化剂的水平的白人美国人（CA）高于非洲裔美国人（AA）。根据2003-2007年美国癌症统计数据，AA的PCa发病率比CA高50%，而AA的死亡率高150%。建议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生物学和侵略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的种族差异。然而，有限的信息是可用的营养调制PCa的侵略性。因此，拟议的研究的目的是确定在何种程度上饮食TAC预测PCa的侵略性。中心假设是，一种新的TAC工具的验证将能够预测氧化应激介导的PCa的风险。我们的工作假设是，PCa攻击性的种族差异部分是由于抗氧化剂摄入量的种族差异。为了验证这一假设，我们的具体目标是：1）确定膳食TAC对新诊断的PCa侵袭性的影响; 2）确定PCa患者的膳食TAC水平是否与血浆、尿液和PCa组织样品中的抗氧化剂-氧化还原状态相关;和3）评估主要的饮食，社会人口，以及生活方式因素对PCa患者饮食TAC的种族差异的影响。该项目将提供关于饮食TAC作为诊断为PCa的男性中可改变的生活方式因素的重要信息，以及它在种族中的差异程度。饮食对PCa攻击性的影响表明生活方式行为因素在PCa结局中的重要性。此外，饮食行为的种族差异的确定可以提供信息，可用于制定适当的干预措施，以降低致命的PCa的风险，并减少PCa死亡率的种族差异。 公共卫生相关性：这项试点研究的目的是测试的假设，即种族差异的前列腺癌的侵略性的一部分是由于种族差异的抗氧化剂摄入量，利用数据的新诊断的前列腺癌患者招募通过北卡罗莱纳州-路易斯安那州前列腺癌项目。这项研究的结果可用于制定适当的干预措施，以降低致命性前列腺癌的风险，并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. PUBLIC HEALTH RELEVANCE: This pilot study aims to test the hypothesis that racial differences in prostate cancer aggressiveness are in part the result of racial differences in antioxidant intake by utilizing data of newly diagnosed prostate cancer patients recruited through the North Carolina-Louisiana Prostate Cancer Project. The findings from this study can be used to develop appropriate interventions to lower the risk of fatal prostate cancer and reduce racial disparities in prostate cancer mortality.