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?

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.

Risk of fracture in men with prostate cancer on androgen deprivation therapy: a population-based cohort study in New Zealand.

BACKGROUND: Androgen deprivation therapy (ADT) administered as a prostate cancer treatment is known to exert multiple side effects including bone deterioration leading to bone fracture. The current analysis is to evaluate the burden of fracture risk in the New Zealand prostate cancer (PCa) population treated with ADT, and to understand the subsequent risk of mortality after a fracture. METHODS: Using datasets created through linking records from the New Zealand Cancer Registry, National Minimal Dataset, Pharmaceutical Collection and Mortality Collection, we studied 25,544 men (aged ≥40 years) diagnosed with PCa between 2004 and 2012. ADT was categorised into the following groups: gonadotropin-releasing hormone (GnRH) agonists, anti-androgens, combined androgen blockade (GnRH agonists plus anti-androgens), bilateral orchiectomy, and bilateral orchiectomy plus pharmacologic ADT (anti-androgens and/or GnRH agonists). RESULTS: Among patients receiving ADT, 10.8 % had a fracture compared to 3.2 % of those not receiving ADT (p < 0.0001). After controlling for age and ethnicity, the use of ADT was associated with a significantly increased risk of any fracture (OR = 2.83; 95 % CI 2.52-3.17) and of hip fracture requiring hospitalisation (OR = 1.82; 95 % CI 1.44-2.30). Those who received combined androgen blockade (OR = 3.48; 95 % CI 3.07-3.96) and bilateral orchiectomy with pharmacologic ADT (OR = 4.32; 95 % CI 3.34-5.58) had the greatest risk of fracture. The fracture risk following different types of ADT was confounded by pathologic fractures and spinal cord compression (SCC). ADT recipients with fractures had a 1.83-fold (95 % CI 1.68-1.99) higher mortality risk than those without a fracture. However, after the exclusion of pathologic fractures and SCC, there was no increased risk of mortality. CONCLUSIONS: ADT was significantly associated with an increased risk of any fracture and hip fracture requiring hospitalisation. The excess risk was partly driven by pathologic fractures and SCC which are associated with decreased survival in ADT users. Identification of those at higher risk of fracture and close monitoring of bone health while on ADT is an important factor to consider. This may require monitoring of bone density and bone marker profiles.

Transcriptomics to study the effect of a Mediterranean-inspired diet on inflammation in Crohn's disease patients.

BACKGROUND: Inflammation is an essential immune response; however, chronic inflammation results in disease including Crohn's disease. Therefore, reducing the inflammation can yield a significant health benefit, and one way to achieve this is through diet. We developed a Mediterranean-inspired anti-inflammatory diet and used this diet in a 6-week intervention in a Crohn's disease population. We examined changes in inflammation and also in the gut microbiota. We compared the results of established biomarkers, C-reactive protein and the micronuclei assay, of inflammation with results from a transcriptomic approach. RESULTS: Data showed that being on our diet for 6 weeks was able to reduce the established biomarkers of inflammation. However, using transcriptomics, we observed significant changes in gene expression. Although no single gene stood out, the cumulative effect of small changes in many genes combined to have a beneficial effect. Data also showed that our diet resulted in a trend of normalising the microbiota. CONCLUSIONS: This study showed that our Mediterranean-inspired diet appeared to benefit the health of people with Crohn's disease. Our participants showed a trend for reduced markers of inflammation and normalising of the microbiota. The significant changes in gene expression after 6 weeks highlighted the increased sensitivity of using transcriptomics when compared to the established biomarkers and open up a new era of dietary intervention studies.

Effects of supplementation with selenium, as selenized yeast, in a healthy male population from New Zealand.

Selenium (Se) supplementation was tested in a group of healthy men from Auckland, New Zealnd with selenized yeast (Selplex, 200 µg/day) as the supplementation mode. A set of biomarkers, including DNA damage levels and seleno-antioxidant enzyme levels, were evaluated at pre- and postsupplementation time points. Supplementation produced significant increases in serum Se levels, red blood cell (RBC) thioredoxin reductase (TR) activity and peroxide-induced DNA damage, when the mean baseline serum Se level was 110 ng/ml. Those with higher baseline serum Se levels gained less serum Se and showed a significant reduction of RBC glutathione peroxidase (GPx) activity by supplementation. The optimum benefits of supplementation on DNA stability are observed when the serum Se level reaches between >120 and <160 ng/ml. However, the most significant observation was that those with highest baseline DNA damage benefit the most from Se supplementation, whereas those having lower baseline DNA damage are disadvantaged. A dose of 200 µg/day selenized yeast was also shown to be a safer supplementation option compared to a similar dose of selenomethionine (SeMet). This study highlights the requirement for prestratification of a population by standing serum Se level and baseline DNA damage level, before any Se supplementation is carried out.

Selenium and its' role in the maintenance of genomic stability.

Selenium (Se) is an essential micronutrient for humans, acting as a component of the unusual amino acids, selenocysteine (Se-Cys) and selenomethionine (Se-Met). Where Se levels are low, the cell cannot synthesise selenoproteins, although some selenoproteins and some tissues are prioritised over others. Characterised functions of known selenoproteins, include selenium transport (selenoprotein P), antioxidant/redox properties (glutathione peroxidases (GPxs), thioredoxin reductases and selenoprotein P) and anti-inflammatory properties (selenoprotein S and GPx4). Various forms of Se are consumed as part of a normal diet, or as a dietary supplement. Supplementation of tissue culture media, animal or human diets with moderate levels of certain Se compounds may protect against the formation of DNA adducts, DNA or chromosome breakage, and chromosome gain or loss. Protective effects have also been shown on mitochondrial DNA, and on telomere length and function. Some of the effects of Se compounds on gene expression may relate to modulation of DNA methylation or inhibition of histone deacetylation. Despite a large number of positive effects of selenium and selenoproteins in various model systems, there have now been some human clinical trials that have shown adverse effects of Se supplementation, according to various endpoints. Too much Se is as harmful as too little, with animal models showing a "U"-shaped efficacy curve. Current recommended daily allowances differ among countries, but are generally based on the amount of Se necessary to saturate GPx enzymes. However, increasing evidence suggests that other enzymes may be more important than GPx for Se action, that optimal levels may depend upon the form of Se being ingested, and vary according to genotype. New paradigms, possibly involving nutrigenomic tools, will be necessary to optimise the forms and levels of Se desirable for maximum protection of genomic stability in all humans.

Zinc in Prostate Health and Disease: A Mini Review.

Introduction-With the high global prevalence of prostate cancer and associated mortalities, it is important to enhance current clinical practices for better prostate cancer outcomes. The current review is towards understanding the value of Zn towards this mission. Method-General information on Zn in biology and multiple aspects of Zn involvement in prostate health and disease were referred to in PubMed. Results-The most influential feature of Zn towards prostate health is its ability to retain sufficient citrate levels for a healthy prostate. Zn deficiencies were recorded in serum, hair, and prostate tissue of men with prostate cancer compared to non-cancer controls. Zn gut absorption, albumin binding, and storage compete with various factors. There are multiple associations of Zn cellular influx and efflux transporters, Zn finger proteins, matrix metalloproteinases, and Zn signaling with prostate cancer outcomes. Such Zn marker variations associated with prostate cancer recorded from biological matrices may improve algorithms for prostate cancer screening, prognosis, and management when coupled with standard clinical practices. Discussion-The influence of Zn in prostatic health and disease is multidimensional, therefore more personalized Zn requirements may be beneficial. Several opportunities exist to utilize and improve understanding of Zn associations with prostate health and disease.

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

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.

Effect of androgen deprivation therapy on serum levels of sclerostin, Dickkopf-1, and osteoprotegerin: a cross-sectional and longitudinal analysis.

Androgen deprivation therapy (ADT) for men with prostate cancer (PCa) results in accelerated bone loss and increased risk of bone fracture. The aim of the present study was to evaluate serum bone markers-sclerostin, Dickkopf-1 (DKK-1) and osteoprotegerin (OPG), in a cohort of 88 PCa patients without known bone metastases, managed with and without ADT, and to analyse their relationship with bone mineral density (BMD) and sex steroids. The cross-sectional analysis between acute-, chronic- and former-ADT groups and PCa controls showed that sclerostin and OPG levels significantly differed between them (p = 0.029 and p = 0.032). Groups contributing to these significant changes were recorded. There were no significant differences in serum DKK-1 levels across the four groups (p = 0.683). In the longitudinal analysis, significant % decreases within groups were seen for DKK-1 [chronic-ADT (- 10.06%, p = 0.0057), former-ADT (- 12.77%, p = 0.0239), and in PCa controls group (- 16.73, p = 0.0022); and OPG levels in chronic ADT (- 8.28%, p = 0.003) and PCa controls group (- 12.82%, p = 0.017)]. However, % changes in sclerostin, DKK-1, and OPG did not differ significantly over 6-months across the evaluated groups. Sclerostin levels showed significant positive correlations with BMD at baseline in the ADT group, while in PCa controls this correlation existed at both baseline and 6-month time points. Sclerostin correlated negatively with testosterone in former ADT users and in PCa controls. Possible prognostic features denoted by parallel increases in sclerostin and BMD are discussed.

Genetic factors in chronic inflammation: single nucleotide polymorphisms in the STAT-JAK pathway, susceptibility to DNA damage and Crohn's disease in a New Zealand population.

The Signal Transducers and Activators of Transcription (STAT)-Janus kinase (JAK) pathway controls signal transduction between cell surface receptors and the nucleus. Two members of that pathway, STAT3 and JAK2, enhanced the risk of Crohn's disease (CD) in recent genome-wide association studies. We replicated these findings in a New Zealand Caucasian case-control cohort, by genotyping two single nucleotide polymorphisms (SNPs) in STAT3 (rs744166(G>A) and rs3816769(C>T)) and rs10758669(A>C) in JAK2, in 302 CD patients and 382 controls. For STAT3, there was a significant decrease in the frequency of the G allele of rs744166 and the C allele of rs3816769 in CD patients as compared with controls (OR=0.76, 95% CI=0.61-0.95, p=0.013; OR=0.71, 95% CI=0.56-0.89, p=0.003). For the JAK2 rs10758669 polymorphism, the homozygous C/C or heterozygous A/C genotypes increased the risk of having CD as compared with the homozygous A/A (OR=1.76, 95% CI=1.26-2.45 and OR=2.36, 95% CI=1.44-3.86, respectively, p=0.0003). Variant alleles in either gene significantly modified the likelihood of inflammatory disease in a colonic location, and of developing extra-intestinal manifestations. The JAK2 variant also strongly enhanced the risk of ileocolonic disease, with stricturing or ileal/stricturing behaviour, requiring a bowel resection. We further studied a subset of our control population, stratified for JAK2 rs10758669 and/or STAT3 rs3816769 genotype. Carrying either the JAK2 or STAT3 IBD risk allele was associated with significantly enhanced susceptibility to DNA damage, as estimated by comet assays in peripheral blood leukocytes, with or without a subsequent oxidative challenge. That is, both risk alleles enhance genomic instability. The JAK2 SNP is part of a haplotype previously associated with enhanced susceptibility to myeloproliferative neoplasms, but functional consequences of the STAT3 variant had not been previously demonstrated. It will be of interest to follow up CD patients carrying either JAK2 or STAT3 risk alleles for development of further secondary effects, including cancer.

Selenium Supplementation and Prostate Health in a New Zealand Cohort.

BACKGROUND: There is variable reporting on the benefits of a 200 µg/d selenium supplementation towards reducing prostate cancer impacts. The current analysis is to understand whether stratified groups receive supplementation benefits on prostate health. METHODS: 572 men were supplemented with 200 µg/d selenium as selinized yeast for six months, and 481 completed the protocol. Selenium and prostate-specific antigen (PSA) levels were measured in serum at pre- and post-supplementation. Changes in selenium and PSA levels subsequent to supplementation were assessed with and without demographic, lifestyle, genetic and dietary stratifications. RESULTS: The post-supplementation selenium (p = 0.002) and the gain in selenium (p < 0.0001) by supplementation were significantly dependent on the baseline selenium level. Overall, there was no significant correlation between changes in PSA and changes in selenium levels by supplementation. However, stratified analyses showed a significant inverse correlation between changes in PSA and changes in selenium in men below the median age (p = 0.048), never-smokers (p = 0.031), men carrying the GPX1 rs1050450 T allele (CT, p = 0.022 and TT, p = 0.011), dietary intakes above the recommended daily intake (RDI) for zinc (p < 0.05), and below the RDI for vitamin B12 (p < 0.001). CONCLUSIONS: The current analysis shows the influence of life factors on prostate health benefits of supplemental selenium.

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

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.

Influence of lifestyle and genetic variants in the aldo-keto reductase 1C3 rs12529 polymorphism in high-risk prostate cancer detection variability assessed between US and New Zealand cohorts.

INTRODUCTION: The prostate-specific antigen (PSA) based prostate cancer (PC) screening is currently being debated. The current assessment is to understand the variability of detecting high-risk PC in a NZ cohort in comparison to a US cohort with better PSA screening facilities. Aldo-keto reductase 1C3 (AKR1C3) is known for multiple functions with a potential to regulate subsequent PSA levels. Therefore, we wish to understand the influence of tobacco smoking and the AKR1C3 rs12529 gene polymorphism in this variability. METHOD: NZ cohort (n = 376) consisted of 94% Caucasians while the US cohort consisted of African Americans (AA), n = 202, and European Americans (EA), n = 232. PSA level, PC grade and stage at diagnosis were collected from hospital databases for assigning high-risk PC status. Tobacco smoking status and the AKR1C3 rs12529 SNP genotype were considered as confounding variables. Variation of the cumulative % high-risk PC (outcome variable) with increasing PSA intervals (exposure factor) was compared between the cohorts using the Kolmogorov-Smirnov test. Comparisons were carried out with and without stratifications made using confounding variables. RESULTS: NZ cohort has been diagnosed at a significantly higher mean age (66.67± (8.08) y) compared to both AA (62.65±8.17y) and EA (64.83+8.56y); median PSA (NZ 8.90ng/ml compared to AA 6.86ng/ml and EA 5.80ng/ml); and Gleason sum (NZ (7) compared EA (6)) (p<0.05). The cumulative % high-risk PC detection shows NZ cohort with a significantly lower diagnosis rates at PSA levels between >6 - <10ng/ml compared to both US groups (p<0.05). These were further compounded significantly by smoking status and genetics. CONCLUSIONS: High-risk PCs recorded at higher PSA levels in NZ could be due to factors including lower levels of PSA screening and subsequent specialist referrals for biopsies. These consequences could be pronounced among NZ ever smokers carrying the AKR1C3 rs12529 G alleles making them a group that requires increased PSA screening attention.

Cancer-preventive Properties of an Anthocyanin-enriched Sweet Potato in the APCMIN Mouse Model.

BACKGROUND: Anthocyanin-rich foods and preparations have been reported to reduce the risk of life-style related diseases, including cancer. The SL222 sweet potato, a purple-fleshed cultivar developed in New Zealand, accumulates high levels of anthocyanins in its storage root. METHODS: We examined the chemopreventative properties of the SL222 sweet potato in the C57BL/6J-APC MIN/+ (APCMIN) mouse, a genetic model of colorectal cancer. APCMIN and C57BL/6J wild-type mice (n=160) were divided into four feeding groups consuming diets containing 10% SL222 sweet potato flesh, 10% SL222 sweet potato skin, or 0.12% ARE (Anthocyanin rich-extract prepared from SL222 sweet potato at a concentration equivalent to the flesh-supplemented diet) or a control diet (AIN-76A) for 18 weeks. At 120 days of age, the mice were anaesthetised, and blood samples were collected before the mice were sacrificed. The intestines were used for adenoma enumeration. RESULTS: The SL222 sweet potato-supplemented diets reduced the adenoma number in the APCMIN mice. CONCLUSIONS: These data have significant implications for the use of this sweet potato variant in protection against colorectal cancer.

Influence of Aldo-keto Reductase 1C3 in Prostate Cancer - A Mini Review.

BACKGROUND: Aldo-keto reductase 1C3 (AKR1C3) is an important oxidoreductase with multiple substrates, that are involved in producing extra-testicular androgens. Its activity is influenced by environmental exposures, as well as by genetic variants. These genetic variants could therefore produce variable testosterone levels and subsequent androgen receptor (AR) activation. This could lead to differential downstream production of the prostate-specific antigen (PSA). As PSA level is used for clinical evaluation of the prostate, these variations could impact prostate cancer (PC) diagnosis, as well as PC management outcomes. This review brings together information with regards to key functions of this enzyme, its relevance in PC, its transcriptional regulation, clinical aspects associated with genetics, differential regulation in cancer and cancer progression, and the types of AKR1C3 inhibitors with future therapeutic value. CONCLUSION: Based on these discussions, hypotheses are forwarded for future applicability of this enzyme and its genetic variants in transformational medical practices in PC. Options for the use of personalised AKR1C3 inhibitor drugs for late stage PC are also discussed.

SNP-SNP interactions as risk factors for aggressive prostate cancer.

Prostate cancer (PCa) is one of the most significant male health concerns worldwide. Single nucleotide polymorphisms (SNPs) are becoming increasingly strong candidate biomarkers for identifying susceptibility to PCa. We identified a number of SNPs reported in genome-wide association analyses (GWAS) as risk factors for aggressive PCa in various European populations, and then defined SNP-SNP interactions, using PLINK software, with nucleic acid samples from a New Zealand cohort. We used this approach to find a gene x environment marker for aggressive PCa, as although statistically gene x environment interactions can be adjusted for, it is highly impossible in practicality, and thus must be incorporated in the search for a reliable biomarker for PCa. We found two intronic SNPs statistically significantly interacting with each other as a risk for aggressive prostate cancer on being compared to healthy controls in a New Zealand population.

Effect of ageing and single nucleotide polymorphisms associated with the risk of aggressive prostate cancer in a New Zealand population.

Prostate cancer is one of the most significant male health concerns worldwide, and various researchers carrying out molecular diagnostics have indicated that genetic interactions with biological and behavioral factors play an important role in the overall risk and prognosis of this disease. Single nucleotide polymorphisms are increasingly becoming strong biomarker candidates to identify the susceptibility of individuals to prostate cancer. We carried out risk association of different stages of prostate cancer to a number of single nucleotide polymorphisms to identify the susceptible alleles in a New Zealand population and checked the interaction with environmental factors as well. We identified a number of single nucleotide polymorphisms to have associations specifically to the risk of prostate cancer and aggressiveness of the disease, and also certain single nucleotide polymorphisms to be vulnerable to the reported behavioral factors. We have addressed "special" environmental conditions prevalent in New Zealand, which can be used as a model for a bigger worldwide study.

Effect of Androgen Deprivation Therapy on Bone Mineral Density in a Prostate Cancer Cohort in New Zealand: A Pilot Study.

INTRODUCTION: Reduction in bone mineral density (BMD) is a common side effect of androgen deprivation therapy (ADT). We aimed to examine the cross-sectional and longitudinal variation in BMD and associated bone markers in patients with nonmetastatic prostate cancer (PCa) managed with and without ADT. METHODS: Bone mineral density of the total body, lumbar spine, femoral neck, ultradistal forearm, and one-third distal radius was measured in 88 patients with PCa without bone metastases at baseline and at 6 months. Patients were categorized into 4 groups: (1) acute ADT (≤6 months), (2) chronic ADT (>6 months), (3) former ADT, and (4) no ADT (controls). Serum levels of bone metabolism markers, procollagen type I N-terminal propeptide (PINP) and C-terminal cross-linking telopeptide of type I collagen (CTX), were also measured. RESULTS: In the cross-sectional analysis, men receiving chronic ADT had significantly lower total body BMD as compared with former ADT users and men with no ADT. In longitudinal analysis, a significant reduction in ultradistal forearm BMD was observed in both acute and chronic ADT users after 6 months (4.08% and 2.7%, P = .012 and .026, respectively). A significant reduction in total body BMD was observed in acute ADT users (2.99%, P = .032). Former ADT users had a significant increase in both lumbar spine and femoral neck BMD (2.84% and 1.59%, P = .008 and .002, respectively). The changes in BMD were not significantly different between acute and chronic ADT users. In the cross-sectional analysis, higher levels of PINP and CTX were observed in acute and chronic ADT users than former ADT users or PCa controls. In longitudinal analysis, the level of serum PINP and CTX did not change significantly from baseline to 6 months in acute, chronic, and former ADT users, or PCa controls, and the percentage change did not differ among the 4 groups. CONCLUSIONS: Men on acute ADT had a similar rate of bone loss to men on chronic ADT. Reversibility in ADT-induced bone loss was observed in those who discontinued ADT. Serum levels of PINP and CTX were higher in acute and chronic ADT users and levels returned to the range of PCa controls when treatment was withdrawn.

Environmental factors and risk of aggressive prostate cancer among a population of New Zealand men - a genotypic approach.

Prostate cancer is one of the most significant health concerns for men worldwide. Numerous researchers carrying out molecular diagnostics have indicated that genetic interactions with biological and behavioral factors play an important role in the overall risk and prognosis of this disease. Single nucleotide polymorphisms (SNPs) are increasingly becoming strong biomarker candidates to identify susceptibility to prostate cancer. We carried out a gene × environment interaction analysis linked to aggressive and non-aggressive prostate cancer (PCa) with a number of SNPs. By using this method, we identified the susceptible alleles in a New Zealand population, and examined the interaction with environmental factors. We have identified a number of SNPs that have risk associations both with and without environmental interaction. The results indicate that certain SNPs are associated with disease vulnerability based on behavioral factors. The list of genes with SNPs identified as being associated with the risk of PCa in a New Zealand population is provided in the graphical abstract.

Aggressive prostate cancer incidence in New Zealand-"united we fall, divided we stand".

Prostate cancer is an important health burden to the healthcare system of any country. However, with the current prostate-specific antigen biomarker having low predictive value even for diagnostic purposes, the challenge is still open to tackle this chronic disease. There have been a number of studies which have indicated and encouraged a multi-directional approach to combat this disease. We have been carrying out a multi-directional approach in order to identify certain New Zealand-specific factors which may be drivers for this cancer and its aggressive forms. These will be explained in further detail in this research letter.

Benefits of Selenium Supplementation on Leukocyte DNA Integrity Interact with Dietary Micronutrients: A Short Communication.

A male cohort from New Zealand has previously shown variability in Selenium (Se) supplementation effects on measured biomarkers. The current analysis is to understand the reasons for variability of the H2O2-induced DNA damage recorded after Se supplementation. We have looked at the variation of demographic, lifestyle, medication, genetic and dietary factors and biomarkers measured at baseline and post-supplementation in these two extreme subgroups A and B. Group A showed increased H2O2-induced DNA damage and group B showed decreased damage after Se supplementation. We have also considered correlations of biomarkers and dietary factors in the complete dataset. The glutathione peroxidase (GPx) activity and DNA damage were significantly lower at post-supplementation in Group B compared to Group A. Post-supplementation, Group B showed a significant reduction in the GPx activity, while Group A showed a significant increase in DNA damage compared to baseline levels. Dietary methionine intake was significantly higher and folate intake was significantly lower in Group B compared to Group A. Se supplementation significantly increased the caspase-cleaved keratin 18 levels in both groups, indicating increased apoptotic potential of this supplement. Parameter correlation with the complete dataset showed dietary methionine to have a significant negative correlation with H2O2-induced DNA damage post-supplementation. The data suggest that Se supplementation is beneficial for the leukocyte DNA integrity only in interaction with the dietary methionine and folate intake.