Prospective Study of Trichomonas vaginalis Infection and Prostate Cancer Incidence and Mortality: Physicians' Health Study

Jennifer R. Stark; Gregory Judson; John F. Alderete; Vasanthakrishna Mundodi; Ashwini S. Kucknoor; Edward L. Giovannucci; Elizabeth A. Platz; Siobhan Sutcliffe; Katja Fall; Tobias Kurth; Jing Ma; Meir J. Stampfer; Lorelei A. Mucci

Disclosures

J Natl Cancer Inst. 2009;101(20):1406-11. 

In This Article

Abstract and Introduction

Abstract

Background A recent nested case–control study found that the presence of antibodies against Trichomonas vaginalis, a common nonviral sexually transmitted infection, was positively associated with subsequent incidence of prostate cancer. We confirmed these findings in an independent population and related serostatus for antibodies against T vaginalis to prostate cancer incidence and mortality.
Methods We conducted a case–control study nested within the Physicians' Health Study that included 673 case subjects with prostate cancer and 673 individually matched control subjects who had available plasma samples. Plasma from blood samples collected at baseline was assayed for antibodies against T vaginalis with an enzyme-linked immunosorbent assay. We used conditional logistic regression to estimate the odds ratios (ORs) of incident prostate cancer, extraprostatic prostate cancer, and cancer that would ultimately progress to bony metastases or prostate cancer–specific death.
Results Although not statistically significant, the magnitude of the association between T vaginalis–seropositive status and overall prostate cancer risk (OR = 1.23, 95% confidence interval [CI] = 0.94 to 1.61) was similar to that reported previously. Furthermore, a seropositive status was associated with statistically significantly increased risks of extraprostatic prostate cancer (OR = 2.17, 95% CI = 1.08 to 4.37) and of cancer that would ultimately progress to bony metastases or prostate cancer–specific death (OR = 2.69, 95% CI = 1.37 to 5.28).
Conclusions This large prospective case–control study obtained further support for an association between a seropositive status for antibodies against T vaginalis and the risk of prostate cancer, with statistically significant associations identified for the risk of extraprostatic prostate cancer and for clinically relevant, potentially lethal prostate cancer.

Introduction

A number of inflammation-related factors have been implicated in prostate cancer risk and progression, but the origin of inflammation is unclear.[1] Infections are one possible source. Trichomonas vaginalis is a common nonviral sexually transmitted infection, with an estimated 174 million annual infections globally.[2] Prevalence in American men ranges from approximately 3% among young men in the general population[3] to 65% among military personnel with nongonococcal urethritis.[4] Little is known about the prevalence of infection in older men; however, in contrast to other common sexually transmitted infections, the infection has been observed to be more prevalent among men aged 25–39 years than in men aged 18–20 years.[3,5] Urethral symptoms associated with T vaginalis tend to be less severe than other common sexually transmitted infections, such as those due to Chlamydia trachomatis or Neisseria gonorrhoeae.[6] Furthermore, more recent studies have found that T vaginalis is associated with asymptomatic infections in 50%–75% of infected men (5,7). Consequently, many men are unaware that they are infected with the parasite.

Men infected with T vaginalis often experience spontaneous resolution, as shown by decreasing rates of infection with time since last sexual contact with an infected partner[8] and natural history studies,[9] in which as many as one-third of men cleared the infection within 2 weeks without treatment.[7] Nevertheless, a smaller proportion of men experience long-term asymptomatic infection.[7,9]T vaginalis can ascend the urethra to the prostate and infect the prostate epithelium,[10,11] and in that epithelium, it is associated with evidence of acute and chronic inflammation.[10] As such, chronic prostatic infection with T vaginalis may initiate an inflammatory response that could increase the risk of developing prostate cancer[10] and increase the risk of disease progression.

A recent case–control study[12] nested in the Health Professionals Follow-up Study found that seroprevalence of T vaginalis infection was positively associated with subsequent prostate cancer risk, with a suggestion of the greatest risk for more aggressive disease that was defined as high Gleason grade disease. As a follow-up on the positive finding between T vaginalis serostatus and prostate cancer risk, we conducted a large nested case–control study within the Physicians' Health Study to further investigate a potential association between T vaginalis serostatus and prostate cancer incidence. We also investigated potential associations between T vaginalis serostatus and subgroups of prostate cancer defined by tumor stage, tumor grade, age at diagnosis, and cancer that ultimately progressed to bony metastases or prostate cancer–specific death.

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