Who suffers most in a low level PSA screening system? A comparison of prostate cancer cohorts from New Zealand and USA

Abstract

According to the New Zealand (NZ) Prostate Cancer Taskforce consideration in 2013, there was no clear evidence to support organised national screening for prostate cancer (PC) with the prostate-specific antigen (PSA) to outweigh the harms of over-diagnosis and over-treatment.Previously we have recorded that the PSA levels are associated with the aldo-keto reductase 1C3 (AKR1C3) rs12529 single nucleotide polymorphism (SNP) compounded by tobacco smoking. Therefore, the current assessment is to understand the variability of detecting high-risk PC in a NZ cohort (with low scale PSA screening) in comparison to a US cohort that had better organised PSA screening until 2012. TheNZcohort from Auckland University study consisted of 95% with Europeanancestry while that of the US cohort from the National Cancer Institute consisted of 47% African Americans (AA) and53% European Americans (EA). Recruitment wascarried out with informed consent and was restricted to the ages 40-90 years. Age,PSA level, disease stage and grade at diagnosiswere collected from the hospital databases.Disease staging followed the tumor–node–metastasis system and a stage IIB and beyond were considered as high-risk disease. At recruitment ethnicity and tobacco smoking status were collected, in addition to a blood sample. All patients were genotyped for the aldo-keto reductase 1C3 (AKR1C3) rs12529 SNP. A total of 376, 202 and 232 NZ, AA and EA men respectively were included in the final analysis.Cumulative % frequency of high-risk prostate cancer was plotted against PSA class intervals and compared between the three groups with and without additional stratifications based on tobacco smoking status and genotype. Our data indicates that lowerlevel PSA screening in NZ render delayed diagnosis of high-risk PC. This impact is compounded by tobacco smoking with worse effects seen among men carrying the AKR1C3 rs12529 CG and GG genotypes.