Interaction between leukocyte aldo-keto reductase 1C3 activity, genotypes, biological, lifestyle and clinical features in a prostate cancer cohort from New Zealand

PLoS One. 2019 May 24;14(5):e0217373. doi: 10.1371/journal.pone.0217373. eCollection 2019.

Abstract

Introduction: Aldo-keto reductase 1C3 (AKR1C3) is known for multiple functions including its catalytic activity towards producing extra-testicular androgen. The present study is towards understanding interaction between biological, lifestyle and genetic impacts of AKR1C3 and their influence on clinical factors in a prostate cancer (PC) cohort from New Zealand (NZ).

Method: Characteristics of 516 PC patients were collected from the Auckland Regional Urology Facility, NZ. These men were genotyped for the AKR1C3 rs12529 single nucleotide polymorphism (SNP). The leukocyte AKR1C3 activity was measured in a sub-cohort. Variability of leukocyte AKR1C3 activity between biological, lifestyle and clinical features as well as correlation between biological and clinical features were assessed with and without genetic stratification.

Results: The leukocyte AKR1C3 activity was associated with age at diagnosis (0.51 vs 0.34 μM coumberol units for >69y vs ≤69y, P = 0.03); and with anatomic stage/prognostic grouping among the AKR1C3 rs12529 CC genotype carriers (0.50 vs 28 μM coumberol units among low- and high-risk groups respectively, P = 0.02). Significant correlation between leukocyte AKR1C3 activity and age at PC diagnosis was also observed (correlation coefficient 0.20 and P = 0.02). Ever- smoking impacted both age and PSA at PC diagnosis among AKR1C3 rs12529 GG and CG genotype carriers respectively. Age at diagnosis significantly correlated with PSA at diagnosis in the main (correlation coefficient 0.29, and P<0.001) and sub-cohorts (correlation coefficient 0.24, and P = 0.01); and those carrying the AKR1C3 rs12529 CG and GG genotypes in both the main (correlation coefficient 0.30, and P<0.001 and correlation coefficient 0.35, and P<0.001 respectively) and sub-cohorts (correlation coefficient 0.43, and P<0.001 and correlation coefficient 0.39, and P = 0.06 respectively); but not with those carrying the CC genotype.

Conclusions: Age dependent PSA thresholds in PC screening could have been valid only in men carrying the AKR1C3 rs12529 CG and GG genotypes in this NZ cohort.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aldo-Keto Reductase Family 1 Member C3 / blood*
  • Aldo-Keto Reductase Family 1 Member C3 / genetics*
  • Body Mass Index
  • Cohort Studies
  • Genotype
  • Humans
  • Kallikreins / blood
  • Leukocytes / enzymology
  • Life Style
  • Male
  • Middle Aged
  • Neoplasm Grading
  • New Zealand
  • Polymorphism, Single Nucleotide
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / enzymology*
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology

Substances

  • AKR1C3 protein, human
  • Aldo-Keto Reductase Family 1 Member C3
  • KLK3 protein, human
  • Kallikreins
  • Prostate-Specific Antigen

Grants and funding

Authors wish to acknowledge the following grantees from New Zealand for their support with the study since 2006 - the A+ Trust, Auckland District Health Board, Auckland, NZ (Grant No. 5461-PG-1204-007-JM), the GoodFellow Trust, Urology Department, Auckland Hospital, Auckland, NZ (Grant No. +3192-JM), the Cancer Society NZ (https://cancernz.org.nz/) (Grant No. 10/08-LRF); and the Auckland Northland Cancer Society, NZ (https://auckland-northland.cancernz.org.nz/) (NK). Funders played no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.