Publication bias is always a concern for meta-analyses. To estimate the number of unpublished studies needed to nullify significant findings to nonsignificance (P > 0.05), we assumed a null effect for unpublished studies and arbitrarily used a variance equivalent to that seen in the study by Honda et al. 17 For STIs, an additional 95 such studies would be needed. More than 200 studies would be needed to nullify the results seen for frequency of sexual activity and 29 to nullify results for number of sexual partners.
These data are supportive of a role of STIs in the etiology of prostate cancer. Consistent associations that are not likely to be explained by publication bias were seen for history of any STI (RR = 1.4), gonorrhea (RR = 1.4), and syphilis (RR = 2.3). The association between prostate cancer and STIs is further supported by an increased RR seen for men whose partners reported STIs (RR = 2.1), men who visited prostitutes (RR = 1.2), men reporting more than 30 sexual partners (RR = 1.3), and men reporting extramarital affairs (RR = 2.2). The 12% of controls reporting STIs in these studies is equivalent to that reported among men 50–59 years of age for a nationwide survey of sexual activity conducted in 1992. 55,56 Based on these data, 30.6% of prostate cancers among men with STIs are attributable to the STI. Assuming causality, the corresponding population attributable risk percentage is 5.8% of all prostate cancers having STI-related etiology.
The higher RR for prostate cancer and STIs seen among population-based studies rather than hospital-based studies could reflect differential misclassification caused by reporting bias, where population-based controls are less likely to report socially undesirable factors such as STIs regardless of their history. Differences seen by study design may instead reflect a high percentage of hospital controls who actually have a history of STIs. Although case-control studies are prone to recall or reporting bias, which may affect reporting of STIs, the recent study by Hayes et al 10 found a higher prevalence of antibodies to Treponema pallidum among prostate cancer cases than in controls, suggesting that recall or reporting bias does not entirely explain the relation. Population-based and hospital-based case-control studies tend to have different advantages and biases; however, both study designs showed an increased association between prostate cancer and STIs.
A mechanism to explain the relation between sexual frequency and prostate cancer is less well understood than that for STIs and prostate cancer. Substantial evidence indicates that hormones play a major role in the etiology of several cancers. 57 Among some men, frequency of sexual activity may be related to hormone levels. It is thought that neoplasms may occur in response to excessive hormonal stimulation of an organ of which the normal function and growth are controlled by hormones. 57 Androgens are required for the growth, maintenance, and functional activities of the prostate gland. 58 Reports suggest that men whose testes have been removed or never developed are not at risk for prostate cancer, 24,59,60 supporting evidence of a hormonal effect on prostate cancer development. Although underlying hormonal factors may contribute to the relation of sexual activity and prostate cancer, human sexual practices are complex and may not directly correlate with hormone levels.
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