Men who are circumcised before their first sexual intercourse have a significantly lower risk for prostate cancer than do uncircumcised men or those who are circumcised after their first sexual encounter, according to an analysis of data on 3,399 men.
The finding of a 15% reduction in relative risk points to sexually transmitted infections and inflammation as possible risk factors for prostate cancer, the authors suggested in a study published online in the journal Cancer.
"These findings are consistent with research showing that an infectious/inflammatory pathway may be involved in prostate carcinogenesis," wrote Dr. Jonathan L. Wright and colleagues at the University of Washington and the Fred Hutchinson Cancer Research Center, both in Seattle (Cancer 2012 March 12 [doi:10.1002/cncr.26653]).
The authors had hypothesized that circumcision reduces the risk for transmission of a sexually transmitted infection (STI), "and that if a [prostate cancer] develops as a result of the STI, only circumcision prior to first sexual intercourse can potentially alter risk" of prostate cancer.
They borrowed data from two population-based, case-control studies of men with prostate cancer, identifying a total of 1,754 cases in the Seattle–Puget Sound SEER (Surveillance, Epidemiology, and End Results) cancer registry. For the 1,645 controls, they used random-digit dialing to identify men from the same area with no prostate cancer, age-matched in 5-year groups.
In all, 68.8% of cases and 71.5% of controls were circumcised. Among all men who reported being circumcised, 91% had the procedure shortly after birth. Circumcision was performed after first sexual intercourse in 3.9% of cases and 2.5% of controls. Circumcision was also more commonly reported in white men (69%) than in black men (43%).
In multivariate regression analysis, the investigators controlled for age, race, prostate-specific antigen (PSA) test within 5 years of diagnosis or reference data, family history of prostate cancer, history of STIs, prior prostatitis, and number of female and male sexual partners. They found that the overall odds ratio for prostate cancer among men who were circumcised before their first sexual intercourse was 0.88 (95% confidence interval, 0.73-0.99).
The researchers also looked at prostate cancer and circumcision status by aggressiveness of disease, with "aggressive" defined as a composite of Gleason score of 7 (4 + 3) or greater; nonlocalized stage; or PSA level greater than 20 ng/mL at the time of diagnosis.
They saw that preintercourse circumcision had borderline associations with lower risk for both less-aggressive (OR, 0.88; 95% CI, 0.74-1.04) and more-aggressive cancers (OR, 0.82; 95% CI, 0.66-1.00).
The reduction in prostate cancer risk with circumcision before first intercourse was observed in whites (OR, 0.87; 95% CI, 0.73-1.02); and blacks (OR, 0.64; 95% CI, 0.39-1.08).
Circumcision has been shown in other studies to be linked to lower rates of STIs, including HIV/AIDS, herpes simplex, syphilis, and chancroid, the authors noted. They suggested that the mucosal lining of the prepuce, which is thin, may develop small tears that provide pathogens with a route to the bloodstream.
"Circumcision may reduce these injuries due to the significant keratinization that occurs following the procedure," they speculated. "In addition, the moist environment under the preputial skin may help pathogens survive for extended periods prior to direct infection. Circumcision removes this protective environment."
The authors pointed to other studies linking circumcision to reduced prostate cancer risk, including a 1987 case-control study in which circumcision was associated with a 50% reduction in relative risk among whites, and a near 40% reduction in blacks (J Natl Cancer Inst. 1987;78:869-74).
The study was supported by National Institute of Health grants and the Fred Hutchinson Cancer Research Center. The authors reported no conflicts of interest. Dr. Freedland said that he had no conflicts of interest.