Prostate Carcinogenesis: The Role of Infection and Inflammation

Cancer, a progressive disease that occurs in a series of well-defined steps. It is induced through mutations, which inactivate tumour suppressor genes or the activation of oncogenes resulting in proliferating cells. Prostate cancer, the most common diagnosed malignancy and source of considerable morbidity and mortality for men around the world, accounts for the 3rd leading cause of death in men in Jamaica. Aside from the contributions of age, race, and family history, which are poorly understood, environmental and lifestyle factors like male sexual behaviour have been suspected of playing a role in prostate carcinogenesis. Recently, there has been increased interest in sexually transmitted infections [STIs] and sexual history as risk factors for prostate cancer. From as early as the 1950s it was postulated that the transmission of a carcinogenic agent through sexual practices may have resulted in an increase in prostate cancer cases.

Inflammation has been hypothesised to increase the risk of numerous malignancies and data suggest that approximately 20% of all human cancers are caused by chronic infection or chronic inflammation. Frequent observations of inflammation close to putative precursor lesions of prostate cancer have sparked renewed interest in the potential influence of sexually transmitted or urogenital infections on prostate carcinogenesis. Studies have shown that many cancers are caused by chronic infection or chronic and longstanding inflammation. The initiation, maintenance and pathology of the inflammatory response depend upon pro- and anti-inflammatory signals, of which the former has multi-factorial epigenetic and genetic cues. Researchers have shown that chronic and longstanding inflammation induced by persistent infection within the host produces preoxynitrite, which interacts with DNA resulting in permanent genomic alterations/mutations that initiate and promote cancer. In addition to the inflammatory process, cells may also be directly transformed via infectious agents inserting oncogenes into the host genome.

There have been numerous studies conducted to ascertain the relationship and risk associated with several STIs and prostate cancer. Several of the earlier studies have shown positive associations between STIs such as gonorrhoea, syphilis and human papillomavirus [HPV] with prostate cancer. However, more recent studies conducted with antibodies against Chlamydia trachomatis, human herpesvirus type 8 [HHV-8], and HPV in relation to prostate cancer have been controversial, moving from no association, weak associations to inverse associations. The association between exposure to specific infectious agents and sexual history may be weak and will vary across populations. Similarly, the association between prostate cancer and the inflammatory cytokines – C-reactive protein [CRP], interleukin-6 [IL-6], and tumour necrosis factor-α [TNF-α] – have been investigated in epidemiological studies with variable results. Some of these studies suggest that the inflammatory markers are more strongly associated with the risk of cancer death than cancer incidence.

Although limited, there is data to support the role of various inflammatory cytokines in the development and progression of prostate cancer. Malignant cells express inflammatory markers and elevated levels of these markers in the blood may signal the presence of an underlying cancer.