Assessment of factors associated with PSA level in prostate cancer cases and controls from three geographical regions

Nishi Karunasinghe,Tsion Zewdu Minas,Shu-Pin Huang,Shuotun Zhu,Megan Goudie,Frank J Jenkins,Alice Wang,Bo-Ying Bao,Lynnette R Ferguson,Arier Lee,Jonathan Masters

doi:10.1038/s41598-021-04116-8

Abstract

It is being debated whether prostate-specific antigen (PSA)-based screening effectively reduces prostate cancer mortality. Some of the uncertainty could be related to deficiencies in the age-based PSA cut-off thresholds used in screening. Current study considered 2779 men with prostate cancer and 1606 men without a cancer diagnosis, recruited for various studies in New Zealand, US, and Taiwan. Association of PSA with demographic, lifestyle, clinical characteristics (for cases), and the aldo–keto reductase 1C3 (AKR1C3) rs12529 genetic polymorphisms were analysed using multiple linear regression and univariate modelling. Pooled multivariable analysis of cases showed that PSA was significantly associated with demographic, lifestyle, and clinical data with an interaction between ethnicity and age further modifying the association. Pooled multivariable analysis of controls data also showed that demographic and lifestyle are significantly associated with PSA level. Independent case and control analyses indicated that factors associated with PSA were specific for each cohort. Univariate analyses showed a significant age and PSA correlation among all cases and controls except for the US-European cases while genetic stratification in cases showed variability of correlation. Data suggests that unique PSA cut-off thresholds factorized with demographics, lifestyle and genetics may be more appropriate for prostate cancer screening.

Highlights

It is being debated whether prostate-specific antigen (PSA)-based screening effectively reduces prostate cancer mortality
The US-AA cases recorded a significantly higher percentage of ever-smokers compared to New Zealand (NZ) and US-EA cases (72% vs 56% for NZ and 61% for US-EA and P < 0.00001)
The percentage alcohol consumption among NZ cases were significantly lower than the US-AA and the US-EA cases (71% vs 85% for US-AA and 90% for US-EA and P < 0.00001)

Summary

Introduction

It is being debated whether prostate-specific antigen (PSA)-based screening effectively reduces prostate cancer mortality. Pooled multivariable analysis of controls data showed that demographic and lifestyle are significantly associated with PSA level. Data suggests that unique PSA cut-off thresholds factorized with demographics, lifestyle and genetics may be more appropriate for prostate cancer screening. The serine protease prostate-specific antigen (PSA) is encoded by the kallikrein-related peptidase 3 (KLK3) gene located in chromosomal region 19q131. Since PSA was considered a marker for prostate cancer screening by the US Food and Drug Administration in 1 9944, US health services had a dedicated prostate cancer screening until the year 2008, when prostate cancer screening with PSA reached a controversial status This was due to the debate as to whether PSA based screening can help reduce prostate cancer-related mortality in men. Comparison of prostate cancer diagnosis data during the pre- and post-USPSTF recommendation eras show that during the latter period US men were diagnosed with more advanced disease compared to the former[11]

Results

Discussion

Conclusion