title: Quality of life effects of androgen deprivation therapy in a prostate cancer cohort in New Zealand: can we minimize effects using a stratification based on the aldo-keto reductase family 1, member C3 rs12529 gene polymorphism?
abstract: BACKGROUND
  Androgen deprivation therapy (ADT) is an effective palliation treatment in men with advanced prostate cancer (PC). However, ADT has well documented side effects that could alter the patient's health-related quality of life (HRQoL). The current study aims to test whether a genetic stratification could provide better knowledge for optimising ADT options to minimize HRQoL effects.
  
  
  METHODS
  A cohort of 206 PC survivors (75 treated with and 131 without ADT) was recruited with written consent to collect patient characteristics, clinical data and HRQoL data related to PC management. The primary outcomes were the percentage scores under each HRQoL subscale assessed using the European Organisation for Research and Treatment of Cancer Quality of Life questionnaires (QLQ-C30 and PR25) and the Depression Anxiety Stress Scales developed by the University of Melbourne, Australia. Genotyping of these men was carried out for the aldo-keto reductase family 1, member C3 (AKR1C3) rs12529 single nucleotide polymorphism (SNP). Analysis of HRQoL scores were carried out against ADT duration and in association with the AKR1C3 rs12529 SNP using the generalised linear model. P-values <0 · 05 were considered significant, and were further tested for restriction with Bonferroni correction.
  
  
  RESULTS
  Increase in hormone treatment-related effects were recorded with long-term ADT compared to no ADT. The C and G allele frequencies of the AKR1C3rs12529 SNP were 53·4 % and 46·6 % respectively. Hormone treatment-related symptoms showed an increase with ADT when associated with the AKR1C3 rs12529 G allele. Meanwhile, decreasing trends on cancer-specific symptoms and increased sexual interest were recorded with no ADT when associated with the AKR1C3 rs12529 G allele and reverse trends with the C allele. As higher incidence of cancer-specific symptoms relate to cancer retention it is possible that associated with the C allele there could be higher incidence of unresolved cancers under no ADT options.
  
  
  CONCLUSIONS
  If these findings can be reproduced in larger homogeneous cohorts, a genetic stratification based on the AKR1C3 rs12529 SNP, can minimize ADT-related HRQoL effects in PC patients. Our data additionally show that with this stratification it could also be possible to identify men needing ADT for better oncological advantage.
authors.affiliation: Auckland Cancer Society Research Centre (ACSRC), Faculty of Medical and Health Sciences (FM&HS), The University of Auckland, Auckland, New Zealand. n.karunasinghe@auckland.ac.nz.
authors.forename: Nishi
authors.identifier: http://orcid.org/0000-0002-6383-4163
authors.initials: N
authors.lastname: Karunasinghe
authors.affiliation: Auckland Cancer Society Research Centre (ACSRC), Faculty of Medical and Health Sciences (FM&HS), The University of Auckland, Auckland, New Zealand.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Discipline of Nutrition and Dietetics, FM&HS, The University of Auckland, Auckland, New Zealand.
authors.forename: Dug Yeo
authors.initials: DY
authors.lastname: Han
authors.affiliation: Auckland Cancer Society Research Centre (ACSRC), Faculty of Medical and Health Sciences (FM&HS), The University of Auckland, Auckland, New Zealand.
authors.forename: Katja
authors.initials: K
authors.lastname: Lange
authors.affiliation: Auckland Cancer Society Research Centre (ACSRC), Faculty of Medical and Health Sciences (FM&HS), The University of Auckland, Auckland, New Zealand.
authors.forename: Shuotun
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Auckland Cancer Society Research Centre (ACSRC), Faculty of Medical and Health Sciences (FM&HS), The University of Auckland, Auckland, New Zealand.
authors.forename: Alice
authors.initials: A
authors.lastname: Wang
authors.affiliation: Auckland Cancer Society Research Centre (ACSRC), Faculty of Medical and Health Sciences (FM&HS), The University of Auckland, Auckland, New Zealand.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Ellett
authors.affiliation: Urology Department, Auckland Hospital, Auckland, New Zealand.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Masters
authors.affiliation: Urology Department, Auckland Hospital, Auckland, New Zealand.
authors.forename: Megan
authors.initials: M
authors.lastname: Goudie
authors.affiliation: Faculty of Health Sciences and Medicine, Bond University, Robina, Australia.|Human Potential Centre, AUT University, Auckland, New Zealand.|Cluster for Health Improvement, Faculty of Science, Health, Education and Engineering, University of the Sunshine Coast, Sippy Downs, Australia.
authors.forename: Justin
authors.initials: J
authors.lastname: Keogh
authors.affiliation: Radiation Oncology Department, Auckland Hospital, Auckland, New Zealand.
authors.forename: Benji
authors.initials: B
authors.lastname: Benjamin
authors.affiliation: Urology Department, Waikato Hospital, Hamilton, New Zealand.
authors.forename: Michael
authors.initials: M
authors.lastname: Holmes
authors.affiliation: Auckland Cancer Society Research Centre (ACSRC), Faculty of Medical and Health Sciences (FM&HS), The University of Auckland, Auckland, New Zealand.|Discipline of Nutrition and Dietetics, FM&HS, The University of Auckland, Auckland, New Zealand.
authors.forename: Lynnette R
authors.initials: LR
authors.lastname: Ferguson
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D000449:Aldehyde Reductase / Q000235:genetics*; D000074425:Aldo-Keto Reductase Family 1 Member C3; D000074408:Aldo-Keto Reductases; D000726:Androgen Antagonists / Q000009:adverse effects*; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000235:genetics*; D008297:Male; D009520:New Zealand; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D011788:Quality of Life
chemical_list: D000726:Androgen Antagonists; D007987:Gonadotropin-Releasing Hormone; D015096:3-Hydroxysteroid Dehydrogenases; D000074408:Aldo-Keto Reductases; D006911:Hydroxyprostaglandin Dehydrogenases; D000449:Aldehyde Reductase; C487341:AKR1C3 protein, human; D000074425:Aldo-Keto Reductase Family 1 Member C3
keywords: AKR1C3 rs12529 single nucleotide polymorphism (SNP); Androgen deprivation therapy (ADT); Health related quality of life (HRQoL)