TRICHOMONOSIS AND PROSTATE CANCER: EVIDENCE OF PROSTATE INFECTION

描述(申请人提供)：尽管越来越多的人认为炎症与前列腺癌的发展有关，但炎症的责任原因(S)仍不清楚。一个有希望的、可能的责任原因是阴道毛滴虫感染(滴虫病)。滴虫病是一种常见的性传播原虫感染，已知涉及前列腺。我们之前在三项流行病学研究中调查了滴虫史和前列腺癌风险，其中两项研究发现阴道毛滴虫血清状态与前列腺癌风险呈正相关，特别是侵袭性疾病或晚期疾病。尽管这些发现是有希望的，但有必要进行更多的研究，以确定它们是否是由于非因果机制，如偶然性或残留混杂。要开始调查这些发现的有效性，一种方法是检查前列腺癌男性患者中前列腺癌滴虫病的证据，假设如果滴虫病确实与前列腺癌的风险相关(至少通过最常见的感染相关致癌机制)，前列腺癌患者中应该观察到过去或现在患有前列腺癌的前列腺癌患者患有前列腺癌的证据。因此，作为调查先前发现有效性的第一个重要步骤，我们建议在华盛顿大学医学院对阴道毛滴虫血清阳性男性前列腺癌患者样本进行一项全面的前列腺癌滴虫病调查。具体地说，在这一男性样本中，我们建议：1)调查当前前列腺癌滴虫病的证据或过去未完全清除的前列腺癌感染中残留的滴虫DNA/抗原；2)调查过去已清除的前列腺滴虫病的证据；以及3)确定滴虫病的血清学证据和前列腺癌证据之间的一致性程度，以告知阴道毛滴虫血清学和前列腺癌风险流行病学研究中可能出现的暴露误分类程度。据我们所知，我们的研究将是第一个全面调查前列腺癌男性前列腺毛滴虫感染的研究。除了它的新颖性，这项研究也是及时和重要的，因为它扩展和支持了最近有希望的流行病学发现，如果最终得到证实，可能会导致前列腺癌的新的初级预防策略，如滴虫病预防、现有感染的筛查和治疗，以及可能的疫苗接种。 公共卫生相关性：这项拟议的研究与公共卫生相关，因为它调查了最近有希望的流行病学发现的有效性，这些发现存在于阴道毛滴虫感染(一种常见的性传播感染)病史和随后的前列腺癌风险之间。如果这些发现最终得到证实，它们可能导致开发新的、简单和廉价的前列腺癌初级预防策略，例如通过减少高危性行为来预防滴虫病；用抗生素筛查和治疗现有的阴道毛滴虫感染；以及可能的疫苗接种。PHS 398/2590(11/07版)页面续格式页面

DESCRIPTION (provided by applicant): Although inflammation is increasingly believed to be involved in the development of prostate cancer, responsible cause(s) of inflammation are still unknown. One promising, possible responsible cause is Trichomonas vaginalis infection (trichomonosis). Trichomonosis is a common, sexually transmitted protozoan infection known to involve the prostate. We previously investigated a history of trichomonosis and risk of prostate cancer in three epidemiologic studies, two of which observed a positive association between T. vaginalis serostatus and prostate cancer risk, particularly aggressive or late-stage disease. Although these findings are promising, additional studies are necessary to determine whether they are due to non-causal mechanisms, such as chance or residual confounding. One way to begin to investigate the validity of these findings is to examine evidence of prostatic trichomonosis in men with prostate cancer under the assumption that, if trichomonosis is truly associated with risk of prostate cancer (at least by the most commonly cited mechanisms of infection-related carcinogenesis), evidence of either past or current prostatic trichomonosis should be observed among men with prostate cancer. Therefore, as the first important step to investigating the validity of previous findings, we propose to conduct a comprehensive investigation of prostatic trichomonosis in a sample of prostate cancer patients enriched for T. vaginalis seropositive men at Washington University School of Medicine. Specifically, in this sample of men, we propose to: 1) investigate evidence of current prostatic trichomonosis or residual trichomonad DNA/antigens from incompletely cleared past prostatic infections; 2) investigate evidence of past, cleared prostatic trichomonosis; and 3) determine the level of agreement between serologic and prostatic evidence of trichomonosis to inform the possible level of exposure misclassification in epidemiologic studies of T. vaginalis serology and prostate cancer risk. To our knowledge, our study will be the first to comprehensively investigate prostatic trichomonosis among men with prostate cancer. In addition to its novelty, this study is also timely and important because it expands upon and supports recent, promising epidemiologic findings, which, if ultimately confirmed, could lead to novel primary preventive strategies for prostate cancer, such as trichomonosis prevention, screening and treatment of existing infections, and possibly vaccination. PUBLIC HEALTH RELEVANCE: The proposed study is relevant to public health because it investigates the validity of recent promising, epidemiologic findings between a history of Trichomonas vaginalis infection (trichomonosis), a common sexually transmitted infection, and subsequent risk of prostate cancer. If these findings are ultimately confirmed, they could lead to the development of novel, simple and inexpensive primary preventive strategies for prostate cancer, such as trichomonosis prevention through reduced high-risk sexual behaviors; screening and treatment of existing T. vaginalis infections with antibiotics; and possibly vaccination. PHS 398/2590 (Rev. 11/07) Page Continuation Format Page