Circumcision Linked to Lower Rates of Prostate Cancer

Roxanne Nelson

March 12, 2012

March 12, 2012 — Circumcision prior to first sexual intercourse appears to be associated with a reduction in the relative risk for prostate cancer.

In a study published online today in Cancer, early circumcision was linked to a 15% reduction in the relative risk for prostate cancer, compared with no circumcision. These findings were observed in both aggressive and less aggressive disease.

"Although the hypothesis and findings of this study are interesting, it is too early to make recommendations about circumcision for prostate cancer prevention," said Siobhan Sutcliffe, PhD, assistant professor in the division of public health sciences at Washington University School of Medicine, St. Louis, Missouri, who was approached for independent comment.

She pointed out that this study is a pooled analysis of 2 observational case–control studies, and compares the proportion of men circumcised before their first sexual intercourse in patients with prostate cancer and in control subjects. "You can draw stronger conclusions from the results of a clinical trial than from a case–control study," she told Medscape Medical News. "This will require many more studies."

The researchers, led by Jonathan L. Wright, MD, affiliate investigator in the public health sciences division at the Fred Hutchinson Cancer Research Center, Seattle, Washington, note that epidemiologic and histologic data support the concept of an inflammatory pathway in prostate cancer development. In addition, there is some evidence of an infectious pathway. Sexually transmitted infections (STI) have been implicated in prostate cancer in some but not all studies.

Some sexually transmitted organisms have been detected in the prostate, including Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, Treponema pallidum, human papillomavirus (HPV), herpes simplex virus, and human herpes virus type 8. The researchers point out that genes that are involved in infection susceptibility, such as RNASEL (ribonuclease L [2′,5′ -oligoisoadenylate synthetase-dependent]), might also play some part in the development of prostate cancer.

In addition, they note that there is research suggesting that circumcised men have a lower risk for STIs, and randomized trials conducted in Africa have shown that circumcision reduces the risk for HIV.

Provocative But More Study Needed

Anthony Y. Smith, MD, who was not involved in the study, pointed out that it is a "provocative study," but much more data are needed.

"Because cervical cancer is so tightly linked to HPV, along with ulcer disease, which is also linked to a pathogen, we are more tuned in to the fact that infectious factors may play more of a role," said Dr. Smith, who is professor and chief of the division of urology in Department of Surgery at the University of New Mexico Cancer Center in Albuquerque.

However, some research on possible infectious pathways has not held up under scrutiny. "There were studies that looked at the murine leukemia-related virus (XMRV) as a potential infectious pathway for prostate cancer development, but recent research has debunked the hypothesis," said Dr. Smith. "The data could not be reproduced by European investigators; they believe that the samples may have been contaminated. This undermined the evidence for XMRV being a human pathogen."

Dr. Smith cautioned that the value of circumcision might be highly dependent on the prevalence of disease in the population. For example, "if the HIV risk is low in the general population, then you are not going to see the effect," he said. "In the African studies, there is high prevalence, so that is why we may be seeing such a strong effect. The flipside is that it may give individuals a false sense of security."

Too Many Confounders

It is extremely difficult to evaluate the effect of circumcision on a wider geographic scale outside of a controlled clinical trial, he noted. As an example, the prevalence of prostate cancer and STIs is similar in the United States, where circumcision is common, and Western Europe, where it is not.

"There are just too many confounders," explained Dr. Smith. "There are so many environmental and other variables that we just don't know about that may play a role in prostate cancer."

"This was a good case–control study, but it will take a lot more study to see if it pans out," he added. "There is also a great deal of controversy with circumcision, so it is way too early to draw any conclusions."

Dr. Sutcliffe agrees. "There are many differences that could exist between the 2 groups that could create or mask an ecologic association, such as differences in the racial distribution of the population, prostate cancer screening practices, sexual practices, sexually transmitted screening practices, the distribution of other known or unknown risk factors for prostate cancer, and so on," she said. "Therefore, it is difficult to interpret ecologic differences or the lack thereof."

"There may be many reasons why ecologic observations don't appear to agree with the authors' finding," she added. "That's why more and different types of studies need to be done before a preventive recommendation can be put forward."

Study Details

Dr. Wright and colleagues collected data from 1754 patients with prostate cancer (68.8% circumcised) and 1645 control subjects (71.5% circumcised) who participated in 1 of 2 population-based case–control studies of prostate cancer. All participants were residents of King County, Washington. Of the circumcised men, 91% reported that the procedure was done shortly after birth.

Overall, they found that men who were circumcised before their first sexual intercourse had a 15% reduction in the relative risk for prostate cancer (95% confidence interval, 0.73 to 0.99), compared with men not circumcised and those circumcised after their first sexual intercourse. Being circumcised after first sexual intercourse was not associated with prostate cancer risk.

The effect did not appear to be modified by factors such as age, STI status, history of prostatitis, family history of prostate cancer, education, or income level (P > .4 for all). In addition, the type of STI did not play a role.

The researchers note that there was a "suggestion of effect modification by race" (P = .07), but the reduction in risk was observed in both white (odds ratio [OR], 0.87) and black (OR, 0.64) men in stratified analyses.

The study was funded by the National Institutes of Health and the Fred Hutchinson Cancer Research Center. The authors have disclosed no relevant financial relationships.

Cancer. Published online March 12, 2012. Abstract


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