TRICHOMONOSIS AND PROSTATE CANCER RISK IN THE PLCO CANCER SCREENING TRIAL

描述(申请人提供)：尽管炎症被越来越多地认为与前列腺癌的发生有关，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)，一种常见的性传播原虫感染，已知涉及前列腺癌。我们之前在以白人男性为主的三项流行病学研究中调查了滴虫病和前列腺癌风险，其中两项研究发现阴道毛滴虫血清状态与前列腺癌，特别是高级别或晚期疾病呈正相关，而第三项研究未发现与非常早期的疾病有关。总而言之，这些发现表明滴虫病可能与侵袭性前列腺癌的风险有关，至少在白人男性中是这样。据我们所知，尽管黑人男性患滴虫病和前列腺癌的风险更高，但还没有研究调查滴虫病和前列腺癌风险之间的关系。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推广到黑人男性(目标1)，并研究滴虫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)中进行滴虫病和前列腺癌风险的流行病学调查。这项拟议的研究将是迄今为止关于滴虫病和前列腺癌风险的最大规模的研究，并将建立在先前在PLCO进行的对性传播感染(STI)和前列腺癌风险的嵌套病例对照研究中的有希望的结果的基础上，在该研究中，作者没有观察到单独的STI与前列腺癌风险之间的关联，但任何STI合并的病史与前列腺癌之间存在适度的正相关，这表明在该研究人群中，另一种未测量的STI，如滴虫感染，可能与前列腺癌的风险有关。这项拟议的研究是及时和创新的，因为它将我们最近观察到的关于以白人男性为主的滴虫病和前列腺癌风险的有希望的发现扩展到黑人男性，而且它具有重要意义，因为我们的发现可能导致为前列腺癌，特别是最有可能发展为致命疾病的前列腺癌开发新的初级预防策略。根据我们的发现，实施初级预防策略将是简单和廉价的，因为滴虫病可以通过安全的性行为容易地预防，并且很容易用目前可用的、廉价的抗生素进行筛查和治疗。可以想象，也可以为这种常见的感染开发一种疫苗。因此，鉴于我们的发现可能对公共卫生和临床产生很大影响，显然需要将其推广到重要的男性亚群(即黑人男性)，并确认我们对侵袭性疾病的提示性发现。 公共卫生相关性：项目简介这项拟议的研究与公共卫生相关，因为它调查了前列腺癌的一种有希望的可能原因(阴道毛滴虫感染或滴虫病)，特别是最有可能致命的前列腺癌。目前，人们对前列腺癌的病因(S)知之甚少，也几乎没有预防策略。因此，如果我们在研究中观察到滴虫病病史与前列腺癌风险之间的正相关关系，这一发现可能会导致更好地了解前列腺癌的发展，以及前列腺癌的新预防策略，如通过减少危险的性行为或疫苗开发来预防滴虫病，以及通过抗生素筛查和治疗现有的感染。

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.