Polyphenols for Cancer Treatment or Prevention

Polyphenols are commonly found in fruits and vegetables, and have been suggested to have protective effects against chronic diseases, such as cancers. They are a diverse group of molecules, many of which possess antioxidant, anti-inflammatory, epigenetic, drug sensitization, and/or modulation of xenobiotic metabolizing enzyme properties. However, there is mixed evidence regarding their protective effects with respect to various cancers. Some of this controversy may be due to the combination of polyphenols administered, synergistic effects of accompanying compounds, bio-accessibility, bioavailability, effect of gut microbiota, and the type of cancer investigated. The purpose of this Special Issue is to present the recent evidence for the effect of polyphenol intake on cancer, as well as mechanisms of action. This Special Issue, entitled "Polyphenols for Cancer Treatment or Prevention", welcomes manuscript submissions of original research, meta-analyses, or reviews of the scientific literature. Authors should focus their manuscripts on polyphenol bioactives or dietary patterns naturally rich in polyphenols that have been identified and used for the prevention and or treatment of cancer

DNA and the chromosome – varied targets for chemotherapy

The nucleus of the cell serves to maintain, regulate, and replicate the critical genetic information encoded by the genome. Genomic DNA is highly associated with proteins that enable simple nuclear structures such as nucleosomes to form higher-order organisation such as chromatin fibres. The temporal association of regulatory proteins with DNA creates a dynamic environment capable of quickly responding to cellular requirements and distress. The response is often mediated through alterations in the chromatin structure, resulting in changed accessibility of specific DNA sequences that are then recognized by specific proteins. Anti-cancer drugs that target cellular DNA have been used clinically for over four decades, but it is only recently that nuclease specific drugs have been developed to not only target the DNA but also other components of the nuclear structure and its regulation. In this review, we discuss some of the new drugs aimed at primary DNA sequences, DNA secondary structures, and associated proteins, keeping in mind that these agents are not only important from a clinical perspective but also as tools for understanding the nuclear environment in normal and cancer cells

Human intervention study to assess the effects of supplementation with olive leaf extract on peripheral blood mononuclear cell gene expression

Olive leaf extract (OLE) has been used for many years for its putative health benefits, but, to date, scientific evidence for the basis of these effects has been weak. Although recent literature has described a link between ailments such as cardiovascular disease, diabetes and cancer and a protective effect of polyphenols in the OLE, the mode of action is still unclear. Here, we describe a double-blinded placebo (PBO)-controlled trial, in which gene expression profiles of peripheral blood mononuclear cells from healthy male volunteers (n = 29) were analysed to identify genes that responded to OLE, following an eight-week intervention with 20 mL daily consumption of either OLE or PBO. Differences between groups were determined using an adjusted linear model. Subsequent analyses indicated downregulation of genes important in inflammatory pathways, lipid metabolism and cancer as a result of OLE consumption. Gene expression was verified by real-time PCR for three genes (EGR1, COX-2 and ID3). The results presented here suggest that OLE consumption may result in health benefits through influencing the expression of genes in inflammatory and metabolic pathways. Future studies with a larger study group, including male and female participants, looking into direct effects of OLE on lipid metabolism and inflammation are warranted

Personalised nutrition and health

This article is one of a series commissioned by The BMJ. Open access fees for the series were funded by SwissRe, which had no input into the commissioning or peer review of the articles.S

One Year Sustainability of Risk Factor Change from a 9-Week Workplace Intervention

We examined the effect of a 9-week diet and physical activity intervention provided in the workplace by a group education session where personal dietary and physical activity goals were proposed. Measurements of anthropometry, fasting blood lipids, glucose and insulin, assays for antioxidant activity (AOA) and questionnaires were completed at 0, 3, 6, 9, and 12 weeks in 50 healthy workers (50% male, mean age 46y). Followup measurements in 39 (56% male) were possible at 52 weeks. At week 3 a group dietary and physical activity “motivational seminar” was held. At week 6, half the group were supplied daily kiwifruit for 3 weeks with cross over at week 9 until week 12. Compared to baseline, lipid, glucose, insulin and AOA measurements were improved at 12 and 52 weeks. Body measurements did not change. Group diet and physical activity advice reinforced over 9 weeks is associated with a sustained improvement in cardiovascular risk factors at 52 weeks

Association Analysis of ULK1 with Crohn's Disease in a New Zealand Population

The gene ULK1 is an excellent candidate for Crohn's disease (CD) due to its role in autophagy. A recent study provided evidence for the involvement of ULK1 in the pathogenesis of CD (Henckaerts et al., 2011). We attempted to validate this association, using a candidate gene SNP study of ULK1 in CD. We identified tagging SNPs and genotyped these SNPs using the Sequenom platform in a Caucasian New Zealand dataset consisting of 406 CD patients and 638 controls. In this sample, we were able to demonstrate an association between CD and several different ULK1 SNPs and haplotypes. Phenotypic analysis showed an association with age of diagnosis 17–40 years and inflammatory behaviour. The findings of this study provide evidence to suggest that genetic variation in ULK1 may play a role in interindividual differences in CD susceptibility and clinical outcome

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

DNase1: No Association with Crohn's Disease in a New Zealand Population

DNase1 has been implicated in a number of immune disorders and is an excellent candidate gene for Crohn's disease (CD). We investigated whether DNase1 SNPs rs1053874 and rs8176938 were associated with CD in a well-characterized New Zealand dataset consisting of 447 cases and 716 controls. Furthermore, we measured serum DNase1 activity levels in a number of CD patients and controls. We did not find any evidence of association for either DNase1 genetic variation or DNase1 activity levels with CD. The lack of association indicates that DNase1 does not play a significant role in predisposing to CD in the New Zealand population

Prostate Cancer: Is It a Battle Lost to Age?

Age is often considered an important non-modifiable risk factor for a number of diseases, including prostate cancer. Some prominent risk factors of prostate cancer include familial history, ethnicity and age. In this review, various genetic and physiological characteristics affected due to advancing age will be analysed and correlated with their direct effect on prostate cancer

IL23R and IL12B SNPs and Haplotypes Strongly Associate with Crohn's Disease Risk in a New Zealand Population

DNA samples from 339 Crohn's disease (CD) and 407 randomly selected controls from the Auckland (New Zealand) IBD project, were genotyped for five common single nucleotide polymorphisms in IL-23R (rs11805303, rs7517847, rs1343151, rs11209026, and rs10889677) and two in IL-12B (rs1363670 and rs6887695). While the IL-12B variants did not show an overall association and other IL23R variants led to minor changes in the risk of CD, rs1343151 and/or rs7517847 variants in the IL-23R gene strongly reduced the risk of developing CD at both allelic and genotype levels. A significantly decreased risk of first diagnosis of childhood CD was observed in individuals carrying the A allele of rs1343151, or between 17–40 y in individuals carrying the G allele in rs7517847 of IL-23R. A significantly decreased risk of ileocolonic or structuring disease was observed in individuals carrying the A allele in either rs11209026 or rs1343151, or the G allele in rs7517847 of IL-23R, and when such individuals did develop the disease, they were unlikely to require a bowel resection. Certain haplotypes very strongly modified risk. There was evidence for interactions of IL-23R variants with the NOD2 wild-type (d/d) genotype. Down-regulating the function of the IL-23R gene may decrease CD risk in the normal population