BOSTON, Jan. 11 -- A history of gonorrhea may translate into a twofold increased risk of bladder cancer for men, researchers here reported.
The association was stronger for invasive and advanced bladder cancer and among smokers, Dominique Michaud, Sc.D., of the Harvard School of Public Health, and colleagues, reported online and in the January issue of the British Journal of Cancer.
Dr. Michaud's team recently reported a positive association between a history of gonorrhea and urinary tract symptoms. On the basis of these earlier findings, the investigators said, gonorrheal infections, generally acquired relatively early in adulthood, may have a long-lasting impact on bladder function.
It is plausible therefore, they said, 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.
Bladder cancer is the fourth most common cancer in men and the sixth most commonly diagnosed cancer in the U.S., the researchers wrote.
Two earlier case-control studies had suggested a link between bladder cancer and gonorrhea, but because both retrospective studies assessed exposure after the cancer diagnosis, recall or selection bias could not be ruled out, the investigators said.
In a prospective cohort of 51,529 predominantly white U.S. men, ages 40 to 75, who were enrolled in the Health Professionals Follow-Up Study, the researchers analyzed 286 incident bladder cancer cases with complete information on gonorrhea.
Men with a history of gonorrhea (2.9%) had twice the risk of bladder cancer (RR 2.07, 95% CI 1.19-3.57). After controlling for a variety of confounders, including smoking history, the risk was still close to two (RR 1.92, CI 1.10-3.33).
In a secondary analysis, the association was slightly stronger after excluding the first two years (1992- 1994) of follow-up (multivariable RR 2.07, CI 1.19-3.60).
Next, the cases were stratified by tumor invasiveness to help eliminate detection bias. The association was not apparent in men with superficial bladder cancer (Ta) and was weak among those with less advanced disease (Ta and T1; RR 1.14, CI 0.50-2.59).
However, it was four times greater in men with invasive cancer (T1-T4) and in advanced cases only (T2-T4; RR 4.07, CI 1.35-12.3).
Further restricting the analysis to invasive TCC produced similar results (RR 2.38, CI 1.00-5.63).
The association with gonorrhea appeared stronger among ever-smokers, although the overall interaction was not statistically significant (P-interaction=0.14), the researchers said.
However, analyzed separately, smoking, not surprisingly, turned out to be bad news, with an almost fivefold greater risk. Compared with never-smokers without a history of gonorrhea, ever-smokers without a history of gonorrhea had a relative risk of 2.19 (CI 1.66-2.89); never-smokers with a history of gonorrhea had an RR of 1.45 (CI 0. 35-6.04), while ever-smokers with a history of gonorrhea had an RR of 4.84 (CI 2.58-9.07).
The association with gonorrhea was similar among ever-smokers with less than 25 pack-years of smoking (RR 1.91, CI 0.87-4.18, yes, versus no history of gonorrhea) and among men with 25-plus pack-years of smoking (RR 2.32, CI 0.95-5.68, yes, versus no history).
Chronic or recurring urinary tract symptom -- incomplete bladder emptying, frequency, intermittency, and urgency -- may increase bladder cancer risk through inflammation or urinary stasis, the researchers said.
Although the overall interaction with smoking was not statistically significant in the current study, a strong association with gonorrhea and bladder cancer was observed among ever-smokers, the researchers said. 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.
Reviewing the study's limitations, the researchers said that as with other STDs under-reporting is possible, although the data were obtained from mailed questionnaires.
In this cohort, 2.9% of men reported a history of gonorrhea, which is slightly higher than the prevalence rate reported in a case-control study. Nonrespondents were similar to men with no history of gonorrhea with respect to behavioral characteristics. Therefore, although it was not possible to rule out the possibility that some non-respondents had gonorrhea, it is unlikely to be a large proportion.
Summing up, the researchers said that in this cohort study, a history of gonorrhea was associated with a statistically significant increase in bladder cancer risk.
The 2.38 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 these observations.
The findings from this prospective study confirm those of two previous case-control studies and warrant further study of the role of the gonorrheal infection itself and bladder inflammation in bladder carcinogenesis, the investigators concluded.