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

<h4>Introduction</h4>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...

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Autores principales:	Nishi Karunasinghe, Eva Symes, Amy Gamage, Alice Wang, Pam Murray, Shuotun Zhu, Megan Goudie, Jonathan Masters, Lynnette R Ferguson
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2863d6f5e91a4d71bdc10c8d79b1d3fc
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spelling	oai:doaj.org-article:2863d6f5e91a4d71bdc10c8d79b1d3fc2021-12-02T20:15:52ZInteraction between leukocyte aldo-keto reductase 1C3 activity, genotypes, biological, lifestyle and clinical features in a prostate cancer cohort from New Zealand.1932-620310.1371/journal.pone.0217373https://doaj.org/article/2863d6f5e91a4d71bdc10c8d79b1d3fc2019-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0217373https://doaj.org/toc/1932-6203<h4>Introduction</h4>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).<h4>Method</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.Nishi KarunasingheEva SymesAmy GamageAlice WangPam MurrayShuotun ZhuMegan GoudieJonathan MastersLynnette R FergusonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 14, Iss 5, p e0217373 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nishi Karunasinghe Eva Symes Amy Gamage Alice Wang Pam Murray Shuotun Zhu Megan Goudie Jonathan Masters Lynnette R Ferguson Interaction between leukocyte aldo-keto reductase 1C3 activity, genotypes, biological, lifestyle and clinical features in a prostate cancer cohort from New Zealand.
description	<h4>Introduction</h4>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).<h4>Method</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.
format	article
author	Nishi Karunasinghe Eva Symes Amy Gamage Alice Wang Pam Murray Shuotun Zhu Megan Goudie Jonathan Masters Lynnette R Ferguson
author_facet	Nishi Karunasinghe Eva Symes Amy Gamage Alice Wang Pam Murray Shuotun Zhu Megan Goudie Jonathan Masters Lynnette R Ferguson
author_sort	Nishi Karunasinghe
title	Interaction between leukocyte aldo-keto reductase 1C3 activity, genotypes, biological, lifestyle and clinical features in a prostate cancer cohort from New Zealand.
title_short	Interaction between leukocyte aldo-keto reductase 1C3 activity, genotypes, biological, lifestyle and clinical features in a prostate cancer cohort from New Zealand.
title_full	Interaction between leukocyte aldo-keto reductase 1C3 activity, genotypes, biological, lifestyle and clinical features in a prostate cancer cohort from New Zealand.
title_fullStr	Interaction between leukocyte aldo-keto reductase 1C3 activity, genotypes, biological, lifestyle and clinical features in a prostate cancer cohort from New Zealand.
title_full_unstemmed	Interaction between leukocyte aldo-keto reductase 1C3 activity, genotypes, biological, lifestyle and clinical features in a prostate cancer cohort from New Zealand.
title_sort	interaction between leukocyte aldo-keto reductase 1c3 activity, genotypes, biological, lifestyle and clinical features in a prostate cancer cohort from new zealand.
publisher	Public Library of Science (PLoS)
publishDate	2019
url	https://doaj.org/article/2863d6f5e91a4d71bdc10c8d79b1d3fc
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Interaction between leukocyte aldo-keto reductase 1C3 activity, genotypes, biological, lifestyle and clinical features in a prostate cancer cohort from New Zealand.

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