TRICHOMONOSIS AND PROSTATE CANCER: EVIDENCE OF PROSTATE INFECTION

描述（由申请人提供）：尽管越来越多的人认为炎症与前列腺癌的发展有关，但炎症的主要原因尚不清楚。一个有希望的，可能的原因是阴道毛滴虫感染（毛滴虫病）。滴虫病是一种常见的性传播原虫感染，已知累及前列腺。我们之前在三项流行病学研究中调查了滴虫病的病史和前列腺癌的风险，其中两项研究发现阴道滴虫血清状态与前列腺癌风险呈正相关，特别是侵袭性或晚期疾病。虽然这些发现是有希望的，但还需要进一步的研究来确定它们是否是由于非因果机制，如偶然或残留混杂。开始调查这些发现的有效性的一种方法是检查前列腺癌男性中前列腺滴虫病的证据，假设滴虫病确实与前列腺癌的风险相关（至少从最常被引用的感染相关癌变机制来看），应该在前列腺癌男性中观察到过去或现在的前列腺滴虫病的证据。因此，作为验证先前发现有效性的第一步，我们建议在华盛顿大学医学院富含阴道滴虫血清阳性男性的前列腺癌患者样本中对前列腺滴虫病进行全面调查。具体来说，在这个男性样本中，我们建议：1)调查目前前列腺滴虫病的证据或残留的滴虫DNA/抗原，这些证据来自过去未完全清除的前列腺感染；2)调查既往已清除的前列腺滴虫病的证据；3)确定毛滴虫病的血清学和前列腺证据之间的一致程度，以告知在阴道滴虫血清学和前列腺癌风险的流行病学研究中可能存在的暴露错误分类程度。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滴虫病的研究。除了它的新颖性之外，这项研究也是及时和重要的，因为它扩展并支持了最近有希望的流行病学发现，如果最终得到证实，可能会导致新的前列腺癌初级预防策略，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。

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