Does diabetes mellitus modify the association between 17q12 risk variant and prostate cancer aggressiveness?

To examine further the relationship between diabetes mellitus (DM), genotype and prostate cancer aggressiveness. Specifically, we sought to evaluate for effect modification between DM, a newly discovered prostate cancer susceptibility locus on chromosome 17q12 (single nucleotide polymorphism rs4430796) and prostate cancer features.

In 593 genotyped men treated with radical prostatectomy (RP), we examined RP features stratified by DM and rs4430796 carrier status.

Despite a significantly higher body mass index among patients with DM, individual pathological features were similar between men with and without DM. Using a dominant model, 17q12 carriers were less likely to have DM and more likely to have a RP Gleason score of >or=7. However, the presence or absence of DM did not modify the relationship between 17q12 susceptibility alleles and pathological features.

Among 17q12 risk allele carriers, there was no significant relationship between DM and adverse tumour features. However, there were relatively few men with DM (7%) in our RP cohort, particularly compared with its 21% prevalence in the USA population aged >60 years. It is unclear whether this reflects selection bias, genetic protection from prostate cancer among patients with DM, or both. Despite these limitations, the present data suggest that DM alone does not appear to modify any association between 17q12 risk alleles with prostate cancer features.