TRICHOMONOSIS AND PROSTATE CANCER RISK IN THE PLCO CANCER SCREENING TRIAL

尽管越来越多的人认为炎症与前列腺癌的发生有关，但炎症的原因尚不清楚。一个有希望的，可能的原因是阴道毛滴虫感染（毛滴虫病），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，其中两项研究发现阴道滴虫血清状态与前列腺癌呈正相关，特别是高级别或晚期疾病，而第三项研究发现与非常早期的疾病没有关联。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较高，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，为了将滴虫病与前列腺癌风险的有希望的发现扩展到黑人男性（Aim 1），并研究滴虫病与侵袭性前列腺癌风险的关系（Aim 2），我们建议在前列腺、肺、结直肠癌和卵巢癌筛查试验（PLCO）中开展滴虫病与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规模最大的滴虫病和前列腺癌风险的调查，并将建立在先前一项关于PLCO性传播感染（STIs）和前列腺癌风险的巢式病例对照研究的有希望的发现之上。在这项研究中，作者观察到个体性传播感染和前列腺癌风险之间没有关联，但任何性传播感染合并史和前列腺癌之间存在适度的正相关，这表明另一种未测量的性传播感染，如滴虫病，在本研究人群中可能与前列腺癌风险相关。这项研究是及时的和创新的，因为它将我们最近观察到的关于毛滴虫病和前列腺癌风险在白人男性中主要存在的有希望的发现扩展到黑人男性，而且它是重要的，因为我们的发现可能导致前列腺癌，特别是最有可能发展为致命疾病的前列腺癌的新的一级预防策略的发展。基于我们的研究结果的一级预防策略的实施将是简单和廉价的，因为滴虫病可以通过安全的性行为很容易地预防，并且很容易用目前可用的廉价抗生素进行筛查和治疗。可以想象，针对这种常见感染也可以研制出疫苗。因此，考虑到我们的研究结果潜在的高公共卫生和临床影响，显然需要扩展到重要的男性亚群（即黑人男性），并确认我们对侵袭性疾病的启发性发现。

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.