Meta-analysis of impact of circumcision and vitamin D on occurrence of prostate cancer: Could they act by suppressing anaerobes colonizing areas of prostatic proliferative inflammatory atrophy?

Abstract

259 Background: There is evidence that some false positive PSA tests can reflect prostatic inflammation that leads to Proliferative Inflammatory atrophy (PIA) that promotes malignant change. Report from circumcision trials in Africa suggest that dominant bacterial flora in un-circumcised men was anaerobes. As circumcised men have a lower incidence of PC this presentation reviews the literature on lack of circumcision and that on Vitamin D deficiency and as a cause of diminished host surveillance that could have potential to synergise as causes of PC. Methods: Three papers reporting incidence of PC in Jewish and non-Jewish men undergoing prostate biopsy for prostate symptoms and 7 series reporting case controlled studies published between 1952 and 2001 have provided data on circumcision and PC risk. There were 10 papers referred to in the IARC 2008 report on plasma 25-hydroxyvitamin D and PC. These have been reviewed together with 8 more published from 2008-10 and 3 that have examined impact of an index of life-time sun exposure on PC risk. Results: The 2 of 3 series of prostate biopsy reported 1951-65 demonstrated significant excess and 1 a non-significant excess of PC in the non-Jewish population. Of the 7 case controlled reported from 1971-2001, only 1 reported significant (OR 1.38) and 1 non-significant (OR 1.15) excess of lack of circumcision in those with prostate cancer, the remaining 6 studies having an excess cancer in those who have been circumcised (OR 0.50 – 0.82 pooled risk 0.70). Only 1 of the 18 plasma 25-OH Vit D series showed significant reduction of PC overall (6 did have reduction in prognostic subsets though 2 had higher incidence in the same sub-groups. In contrast all 3 series that have examined an index of life-time sun exposure showed significant reduction of PC (OR 0.18, 0.32 and 0.52 n= 850). Conclusions: The inconsistencies in the circumcision data suggest that it is not the surgery alone but the confounding variable of the hygiene rules that at least contribute to the reduced PC in Jewish men, and mirrors the similar differences seen in the protective value against AIDS of circumcision in Xhosa African and Asian Muslim men.