TRICHOMONOSIS AND PROSTATE CANCER RISK IN THE PLCO CANCER SCREENING TRIAL

描述（由申请人提供）： 摘要 尽管人们越来越多地认为炎症与前列腺癌发生有关，但引起炎症的原因仍不清楚。一个有希望的、可能的原因是阴道毛滴虫感染（毛滴虫病），这是一种常见的性传播原虫感染，已知前列腺受累。我们之前在三项主要针对白人男性的流行病学研究中调查了滴虫病和前列腺癌的风险，其中两项研究观察到阴道滴虫与前列腺癌之间存在正相关，特别是高级别或晚期疾病，而第三项研究则观察到与非常早期疾病没有相关性。总的来说，这些发现表明滴虫病可能与侵袭性前列腺癌的风险有关，至少在白人中是这样。据我们所知，没有研究调查黑人男性滴虫病和前列腺癌风险之间的关联，尽管他们患滴虫病和前列腺癌的风险较高。因此，为了将我们关于滴虫病和前列腺癌风险的有希望的发现扩展到黑人（目标 1），并调查滴虫病和侵袭性前列腺癌风险之间的关系（目标 2），我们建议在前列腺癌、肺癌、结直肠癌和卵巢癌筛查试验（PLCO）中对滴虫病和前列腺癌风险进行流行病学调查。拟议的研究将是迄今为止对滴虫病和前列腺癌风险最大规模的调查，并将建立在先前一项关于 PLCO 中性传播感染 (STI) 和前列腺癌风险的巢式病例对照研究的有希望的结果的基础上，其中作者观察到个体 STI 与前列腺癌风险之间没有关联，但任何 STI 病史与前列腺癌之间存在适度的正相关，这表明另一种未测量的 STI，如滴虫病，可能与本研究人群中的前列腺癌风险相关。这项拟议的研究是及时且具有创新性的，因为它将我们最近观察到的关于主要是白人男性的毛滴虫病和前列腺癌风险的有希望的发现扩展到了黑人男性，而且意义重大，因为我们的发现可能导致针对前列腺癌，特别是最有可能进展为致命疾病的前列腺癌制定新的一级预防策略。基于我们的研究结果的一级预防策略实施起来既简单又便宜，因为滴虫病可以通过安全的性行为轻松预防，并且可以使用目前可用的廉价抗生素轻松筛查和治疗。可以想象，还可以针对这种常见感染开发疫苗。因此，考虑到我们的研究结果可能对公共卫生和临床产生重大影响，显然需要扩展到重要的男性亚群（即黑人），并确认我们对侵袭性疾病的提示性发现。 公共健康相关性：项目叙述拟议的研究与公共健康相关，因为它调查了前列腺癌，特别是最有可能致命的前列腺癌的一个有希望的、可能的原因（阴道毛滴虫感染或毛滴虫病）。目前对前列腺癌的病因知之甚少，也很少有预防策略。因此，如果我们在研究中观察到滴虫病史与前列腺癌风险之间存在正相关，这一发现可能会导致更好地了解前列腺癌的发展，并制定新的前列腺癌预防策略，例如通过减少危险性行为或开发疫苗来预防滴虫病，以及通过抗生素筛查和治疗现有感染。

DESCRIPTION (provided by applicant): ABSTRACT Although inflammation is increasingly believed to be involved in prostate carcinogenesis, responsible cause(s) of inflammation are still unclear. One promising, possible responsible cause is Trichomonas vaginalis infection (trichomonosis), a common, sexually transmitted protozoan infection with known prostate involvement. We previously investigated trichomonosis and prostate cancer risk in three epidemiologic studies of predominantly White men, two of which observed a positive association between T. vaginalis serostatus and prostate cancer, particularly high-grade or late-stage disease, while the third observed no association with very early-stage disease. Collectively, these findings suggest that trichomonosis may be associated with risk of aggressive prostate cancer, at least in White men. To our knowledge, no studies have investigated associations between trichomonosis and prostate cancer risk among Black men, despite their higher risks of both trichomonosis and prostate cancer. Therefore, to extend our promising findings for trichomonosis and prostate cancer risk to Black men (Aim 1), and to investigate the relation between trichomonosis and aggressive prostate cancer risk (Aim 2), we propose to conduct an epidemiologic investigation of trichomonosis and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). The proposed study will be the largest investigation of trichomonosis and prostate cancer risk to date, and will build upon promising findings from a previous nested case-control study of sexually transmitted infections (STIs) and prostate cancer risk in PLCO, in which the authors observed no associations between individual STIs and risk of prostate cancer, but a modest positive association between a history of any STIs combined and prostate cancer, suggesting that another unmeasured STI, such as trichomonosis, might be associated with risk of prostate cancer in this study population. The proposed study is timely and innovative because it extends our recently observed promising findings for trichomonosis and prostate cancer risk among predominantly White men to Black men, and it is significant because our findings could lead to the development of novel primary prevention strategies for prostate cancer, particularly prostate cancer with the greatest potential for progression to fatal disease. Primary prevention strategies based on our findings would be simple and inexpensive to implement because trichomonosis can be easily prevented by safe sexual behavior, and easily screened and treated with currently available, inexpensive antibiotics. A vaccine could also conceivably be developed for this common infection. Therefore, given the potentially high public health and clinical impact of our findings, extension to important sub-groups of men (i.e., Black men), and confirmation of our suggestive findings for aggressive disease are clearly needed. PUBLIC HEALTH RELEVANCE: PROJECT NARRATIVE The proposed study is relevant to public health because it investigates a promising, possible cause (Trichomonas vaginalis infection or trichomonosis) of prostate cancer, particularly prostate cancer that is most likely to be fatal. Very little is currently known about the cause(s) of prostate cancer, and few prevention strategies exist. Therefore, if we observe a positive association between a history of trichomonosis and prostate cancer risk in our study, this finding could lead to a better understanding of prostate cancer development, and novel prevention strategies for prostate cancer, such as prevention of trichomonosis through reduced risky sexual behaviors or vaccine development, and screening and treatment of existing infections by antibiotics.