In this prospective study, we observed a two-fold increase in bladder cancer risk among men with a history of gonorrhoea. The association was stronger for invasive and advanced bladder cancer and among current smokers.
Chronic or recurring urinary infections may increase bladder cancer risk through inflammation or urinary stasis. Urinary tract infections have been associated with bladder cancer risk in many case–control studies (Howe et al, 1980
; Kantor et al, 1984
; Claude et al, 1986
; Piper et al, 1986
; Gonzalez et al, 1991
; La Vecchia et al, 1991
). In one study, increased risk was observed among individuals who reported their first UTI 15 or more years before diagnosis (OR=2.3, 95% CI=1.0–5.2) (La Vecchia et al, 1991
). In another case–control study, associations with UTI were strongest for advanced cancers (OR=4.6, 95% CI=2.4–8.9) (Kantor et al, 1984
Lower urinary tract symptoms include incomplete bladder emptying, frequency, intermittency, urgency, and hesitancy, and we recently reported a positive association between history of gonorrhoea and such symptoms in this cohort (RR=1.63, 95% CI=1.14–2.33) (Sutcliffe et al, 2005
). Based on these findings, gonorrhoeal infections, generally acquired relatively early in adulthood, may have a long-lasting impact on bladder function. It is plausible therefore that the inflammation producing these urinary symptoms, or increased urinary stasis from incomplete bladder emptying, or a combination of these could be involved in bladder carcinogenesis.
Although the interaction with smoking was not statistically significant in the current study, we observed a strong association with gonorrhoea and bladder cancer among ever smokers. The strength of the association among individuals with a high or a low pack-year smoking history was similar, suggesting that residual confounding by number of pack-years was unlikely. Effect modification by smoking of the UTI and bladder cancer association has been reported in two studies (Kantor et al, 1984
; La Vecchia et al, 1991
). In one, when compared to never smokers with no history of UTI, ever smokers with a history of UTI had an RR of 10.3 (95% CI=5.3–20.1), never smokers with a history of UTI had an RR of 3.2 (95% CI=1.6–6.3), and ever smokers with no history of UTI had an RR of 2.4 (95% CI=1.6–3.6) (La Vecchia et al, 1991
The strengths of this study include its prospective design, which precludes recall bias, a large number of bladder cancer cases, and high follow-up rates. In addition, we conducted secondary analyses to address potential biases that may have occurred. We explored the possibility that a person with a history of gonorrhoea might be more likely to get a medical work-up that would lead to the detection of bladder cancer. If detection bias was present, we would expect less advanced or noninvasive tumours to be more commonly reported among those with a history of gonorrhoea. However, we observed stronger associations between gonorrhoea and bladder cancer risk among those who had advanced or invasive disease and no association among those with noninvasive disease. Furthermore, the association strengthened after removing the first 2 years of follow-up, suggesting that detection bias or reverse causation is unlikely to explain our findings.
As with other STDs, under reporting is probable, especially in face-to-face interviews where individuals may be uncomfortable reporting a positive history. Our data on gonorrhoea was obtained from mailed questionnaires and fewer than 9% of participants did not answer that question; we do not know why these men did not respond, but it is unlikely that nonrespondents were all positive for gonorrhoea. In this cohort, 2.9% of men reported a history of gonorrhoea, which is slightly higher than the prevalence rate reported in a case–control study on STD and prostate cancer among white men (2.5%) (Hayes et al, 2000
). If all nonrespondents were positive, the prevalence of gonorrhoea would be 11% in this educated population of health professionals, which is unlikely. Furthermore, nonrespondents were similar to men with no history of gonorrhoea with respect to behavioural characteristics. Therefore, although we cannot rule out the possibility that some nonrespondents had gonorrhoea, it is unlikely to be a large proportion, and results would only be biased if the relationship between gonorrhoea and bladder cancer was different in responders and nonresponders.
In this cohort study of men, a history of gonorrhoea was associated with a statistically significant increase in bladder cancer risk (P-value=0.02). The 2.4-fold increase in risk observed for invasive disease and the lack of association among men with superficial disease suggest that detection bias is unlikely to explain our observation. Our findings from a prospective study confirm those of two previous case–control studies and warrant further study of the role of gonorrhoea and inflammation in bladder carcinogenesis.