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 treatmentrelated 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 cancerspecific 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

Molecular Characterization of the Onset and Progression of Colitis in Inoculated Interleukin-10 Gene-Deficient Mice: A Role for PPARα

The interleukin-10 gene-deficient (Il10−/−) mouse is a model of human inflammatory bowel disease and Ppara has been identified as one of the key genes involved in regulation of colitis in the bacterially inoculated Il10−/− model. The aims were to (1) characterize colitis onset and progression using a histopathological, transcriptomic, and proteomic approach and (2) investigate links between PPARα and IL10 using gene network analysis. Bacterial inoculation resulted in severe colitis in Il10−/− mice from 10 to 12 weeks of age. Innate and adaptive immune responses showed differences in gene expression relating to colitis severity. Actin cytoskeleton dynamics, innate immunity, and apoptosis-linked gene and protein expression data suggested a delayed remodeling process in 12-week-old Il10−/− mice. Gene expression changes in 12-week-old Il10−/− mice were related to PPARα signaling likely to control colitis, but how PPARα activation might regulate intestinal IL10 production remains to be determined

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 abstrac

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

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

Selenium Supplementation and Prostate Health in a New Zealand Cohort

Background: There is variable reporting on the benefits of a 200 &mu;g/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 &micro;g/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 &lt; 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 &lt; 0.05), and below the RDI for vitamin B12 (p &lt; 0.001). Conclusions: The current analysis shows the influence of life factors on prostate health benefits of supplemental selenium

Molecular characterization of the onset and progression of colitis in inoculated interleukin-10 gene-deficient mice: a role for PPARcx

The interleukin-10 gene-deficient (Il10−/−) mouse is a model of human inflammatory bowel disease and Ppara has been identified as one of the key genes involved in regulation of colitis in the bacterially inoculated Il10−/− model. The aims were to (1) characterize colitis onset and progression using a histopathological, transcriptomic, and proteomic approach and (2) investigate links between PPARα and IL10 using gene network analysis. Bacterial inoculation resulted in severe colitis in Il10−/− mice from 10 to 12 weeks of age. Innate and adaptive immune responses showed differences in gene expression relating to colitis severity. Actin cytoskeleton dynamics, innate immunity, and apoptosis-linked gene and protein expression data suggested a delayed remodeling process in 12-week-old Il10−/− mice. Gene expression changes in 12-week-old Il10−/− mice were related to PPARα signaling likely to control colitis, but how PPARα activation might regulate intestinal IL10 production remains to be determined

An Investigation into the Association between DNA Damage and Dietary Fatty Acid in Men with Prostate Cancer

Prostate cancer is a growing problem in New Zealand and worldwide, as populations adopt a Western style dietary pattern. In particular, dietary fat is believed to be associated with oxidative stress, which in turn may be associated with cancer risk and development. In addition, DNA damage is associated with the risk of various cancers, and is regarded as an ideal biomarker for the assessment of the influence of foods on cancer. In the study presented here, 20 men with prostate cancer adhered to a modified Mediterranean style diet for three months. Dietary records, blood fatty acid levels, prostate specific antigen, C-reactive protein and DNA damage were assessed pre- and post-intervention. DNA damage was inversely correlated with dietary adherence (p = 0.013) and whole blood monounsaturated fatty acids (p = 0.009) and oleic acid (p = 0.020). DNA damage was positively correlated with the intake of dairy products (p = 0.043), red meat (p = 0.007) and whole blood omega-6 polyunsaturated fatty acids (p = 0.015). Both the source and type of dietary fat changed significantly over the course of the dietary intervention. Levels of DNA damage were correlated with various dietary fat sources and types of dietary fat