Sexually Transmitted Infections and Risk of Prostate Cancer: Review of Historical and Emerging Hypotheses

Abstract

ABSTRACT/SUMMARYSince the early 1950s when sexually transmitted infections (STIs) were first proposed as a possible risk factor for prostate cancer, numerous epidemiologic studies have been conducted.Initially, these studies were primarily small case-control studies with retrospective, self-reported assessment of a narrow range of STIs, typically either any STIs, or gonorrhea and syphilis.However, as new STIs have been discovered/recognized, new and better tests to detect histories of STIs have been developed, and new resources for prostate cancer research have been created, epidemiologic studies have expanded to include a wider range of STIs, and have moved towards more rigorous, prospective study designs and serologic assessment of STI histories. The results of these studies are reviewed and discussed, as well as possible new avenues of research, such asTrichomonas vaginalis infection and infections not typically considered to be sexually transmitted. 3 EARLY HYPOTHESES FOR SEXUALLY TRANSMITTED INFECTIONS AND PROSTATE CANCEREarly hypotheses related to a sexually transmitted etiology of prostate cancer were initially motivated by contemporary, epidemiologic patterns of prostate cancer occurrence. In the early 1950s, Ravich and Ravich [1, 2] noted a higher prostate cancer prevalence among mainly uncircumcised non-Jewish than circumcised Jewish men, similar to patterns for penile cancer and cervical cancer among female partners of these men, leading them to propose that observed patterns might be explained by sexual transmission of a virus or other carcinogenic agent contained within the smegma of uncircumcised males. Subsequent investigators [3][4][5] further proposed additional hypotheses related to infection, sexual behavior, and sexual frustration to explain other contemporary patterns of prostate cancer occurrence by marital, paternal, and racial status. Together, these observations and hypotheses led to a series of investigations beginning in the early 1970s to examine possible associations between STIs and sexual behavior in relation to prostate cancer. Selection of STIs STI markers:Most early investigations of STIs and prostate cancer assessed either a history of any STIs or individual histories of gonorrhea and syphilis as markers or possibly vectors of the potentially causative STI or sexual behavior [6][7][8][9]. These STIs were likely selected because they were the most common, well-known, and symptomatic STIs at the time, making them also more readily assessed by self-report, medical record abstraction, or registry query. Prostate inflammation:Other early studies focused specifically on gonorrhea because it frequently led to 4 secondary gonococcal prostatitis in the pre-and early-antibiotic era, and because prostate inflammation had previously been hypothesized as a cause of atrophy and subsequent prostate cancer ([9-11] and references therein). This inflammation-atrophy-prostate cancer hypothesis has since gained further support with the observation of morphological and epigenetic transitions betwe...

Prostate Involvement During Sexually Transmitted Infections as Measured by Prostate Specific Antigen Concentration

“…While all STIs had the potential for prostate involvement (Sutcliffe andPlatz, 2007, 2008), chlamydia cases were most likely to have a large PSA rise, followed by gonorrhoea cases, whereas NCNGU cases were no more likely to have a rise than controls. One possible reason for these differences may be likelihood of symptoms as a possible marker of duration of infection.…”

“…Despite ongoing interest in the role of exudative sexually transmitted infections (STIs; i.e., those that cause an inflammatory discharge) in prostate carcinogenesis (Sutcliffe, 2010), few studies have examined the likelihood of prostate involvement during infection, particularly in the current antibiotic era (Sutcliffe and Platz, 2007). We previously investigated this question by measuring serum prostate-specific antigen (PSA) as a marker of prostate infection, inflammation, and/or cell damage in a small study of young, African-American STI patients (Sutcliffe et al, 2006).…”

What’s the Damage? The Impact of Pathogens on Pathways that Maintain Host Genome Integrity

“…The flagellate Trichomonas vaginalis has been linked to cervical and prostate cancer (Sutcliffe, 2010). Malaria was linked to development of endemic Burkitt lymphoma (eBL) by Denis Burkitt in Sub-Saharan Africa in the 1960’s, and malaria antibodies have been detected in cancer patients.…”

Persistence of Trichomonas vaginalis serostatus in men over time

“…Other determinants of both seroconversion and antibody persistence might be the number of repeat Tv infections, the duration of infection, and the development of complications, as each of these has been found to influence seroconversion and antibody persistence for other non-lifelong STIs. Importantly, these characteristics are also believed to be relevant for carcinogenesis [2]. Finally, studies with longer time between repeat specimens are necessary to inform the long-term persistence of Tv antibodies, as our study was limited to three years.…”

“…This common protozoan infection has been proposed as a possible risk factor for prostate cancer (PCa) for several reasons, including its ability to infect and elicit inflammation within the prostate; its propensity to establish persistent, subclinical infections; its ability to damage prostate epithelium, alter local polyamine levels, inhibit apoptosis, and upregulate proto-oncogenes; and its more common occurrence in African-American men, who are at highest risk of PCa [2, 3]. A recent study also found that Tv macrophage migration inhibitory factor, a human proinflammatory cytokine homolog, increases growth and invasiveness of benign and malignant prostate cells in vitro [4], and two of three recent sero-epidemiologic studies observed positive associations between a history of Tv infection and risk of PCa, particularly high-grade and metastatic/fatal disease [5, 6].…”