Varying parameters associated with prostate-specific antigen (PSA) level in prostate cancer cases and controls from three geographical regions

Abstract

Abstract Introduction It is still being debated whether PSA-based screening effectively reduces prostate cancer mortality in men. Some of the uncertainty could be related to existing deficiencies in the age-based PSA thresholds that are currently used, without consideration of other factors. Methods The current analysis considered PSA associations with demographic, lifestyle, and clinical characteristics, and genotype data for the aldo-keto reductase 1C3 (AKR1C3) rs12529 genotype. Cohorts analysed included a total of 2781 men with prostate cancer and 1606 men without a cancer diagnosis, recruited for various studies in New Zealand (NZ), the United States of America (US-EA - European Americans and US-AA - African Americans), and Taiwan (TW1 and TW2 - advanced and localised prostate cancer groups respectively). Factors potentially affecting PSA level were analysed using multiple linear regression and univariate modeling. Results Multivariable analysis using the pooled data from all cases showed that PSA was significantly associated with ethnicity, disease prognostic stage (DPS), Gleason sum score (GSS), age at diagnosis (AaD), tobacco smoking, and BMI. An interaction between ethnicity and AaD modified the association of PSA among the aforementioned variables. However, similar analyses within independent case cohorts showed that factors associated with PSA were rather specific for each case cohort. Among the factors significantly associated with PSA were GSS for US-EA, US-AA, and TW2; DPS for NZ-European and TW1, AaD and tobacco smoking for NZ-European; and BMI for US-AA and TW1 cases. Multivariable analysis of the combined US-EA, US-AA, and NZ-European controls also showed that ethnicity, age, BMI, and tobacco smoking are significantly associated with PSA level. However, independent analyses of control cohorts indicated that PSA is significantly associated with age among all cohorts while the association of other factors varied between cohorts. Univariate analyses showed a significant age and PSA correlation among all cases and control cohorts except for the US-EA cases. Univariate analyses with genetic stratification in case cohorts showed variability in significant age and PSA correlation.

Conclusion The Association of PSA with BMI and tobacco smoking at the expense of age in some tested cohorts could be indicating a changing paradigm of parameters associated with PSA since the PSA test was first established in 1994. Variation in the correlation between age at diagnosis and PSA in genetically stratified groups in the cases cohorts may indicate the insufficiency of ‘one size fits all’ age-based PSA thresholds for prostate cancer screening. Further expanded studies are needed to verify these findings.