Effect of green tea and lycopene on the insulin-like growth factor system: the ProDiet randomized controlled trial.

Whether prostate cancer (PCa) may be preventable by dietary interventions can be assessed in randomized trials using intermediate biomarkers of cancer risk or progression. We investigated whether lycopene or green tea modify circulating insulin-like growth factor (IGF) peptides in men at increased risk of PCa. Participants (aged 50-69 years) in one centre in the UK wide PCa testing and treatment trial (ProtecT) with prostate specific antigen between 2.0 and 2.95 ng/ml or negative biopsies, were randomized to daily lycopene (n = 44 assigned 15 mg capsules/day; 44 assigned a lycopene-rich diet; 45 assigned placebo) and green tea (n = 45 assigned 600 mg/day epigallocatechin gallate; 45 assigned green tea drink; 43 assigned placebo) for 6 months. The interventions significantly elevated the primary outcomes, serum epigallocatechin gallate and lycopene at 6 months of follow-up. We report here an exploratory analysis in which serum IGF-I, IGF-II, IGF binding protein (BP)-2 and IGFBP-3 were measured at baseline and 6 months of postintervention. A total of 133 men were randomized (34% of eligible men approached) and 130 had follow-up IGF peptides (98%). In intention-to-treat analyses, there was only weak evidence that lycopene or green tea influenced some aspects of serum IGF-I, IGF-II, IGFBP-2 or IGFBP-3. In men randomized to lycopene supplements, IGFBP-2 was nonsignificantly (50.9 ng/ml; 95% confidence interval: -51.2-152.9, P = 0.3) higher in comparison to placebo, whereas in men randomized to green tea supplements, IGFBP-3 was nonsignificantly (205.2 ng/ml; 95% confidence interval: -583.3-172.9, P = 0.3) lower than with placebo. In this small, pilot randomized controlled trial, there was little evidence that lycopene or green tea interventions influenced serum levels of IGF-I, IGF-II, IGFBBP-3 and IGFBP-2. However, the effects were imprecisely estimates and some observed trends may justify larger trials.

Investigating the effects of lycopene and green tea on the metabolome of men at risk of prostate cancer: The ProDiet randomised controlled trial.

Lycopene and green tea consumption have been observationally associated with reduced prostate cancer risk, but the underlying mechanisms have not been fully elucidated. We investigated the effect of factorial randomisation to a 6-month lycopene and green tea dietary advice or supplementation intervention on 159 serum metabolite measures in 128 men with raised PSA levels (but prostate cancer-free), analysed by intention-to-treat. The causal effects of metabolites modified by the intervention on prostate cancer risk were then assessed by Mendelian randomisation, using summary statistics from 44,825 prostate cancer cases and 27,904 controls. The systemic effects of lycopene and green tea supplementation on serum metabolic profile were comparable to the effects of the respective dietary advice interventions (R2 = 0.65 and 0.76 for lycopene and green tea respectively). Metabolites which were altered in response to lycopene supplementation were acetate [ß (standard deviation difference vs. placebo): 0.69; 95% CI = 0.24, 1.15; p = 0.003], valine (ß: -0.62; -1.03, -0.02; p = 0.004), pyruvate (ß: -0.56; -0.95, -0.16; p = 0.006) and docosahexaenoic acid (ß: -0.50; -085, -0.14; p = 0.006). Valine and diacylglycerol were lower in the lycopene dietary advice group (ß: -0.65; -1.04, -0.26; p = 0.001 and ß: -0.59; -1.01, -0.18; p = 0.006). A genetically instrumented SD increase in pyruvate increased the odds of prostate cancer by 1.29 (1.03, 1.62; p = 0.027). An intervention to increase lycopene intake altered the serum metabolome of men at risk of prostate cancer. Lycopene lowered levels of pyruvate, which our Mendelian randomisation analysis suggests may be causally related to reduced prostate cancer risk.

The importance of dietary change for men diagnosed with and at risk of prostate cancer: a multi-centre interview study with men, their partners and health professionals.

BACKGROUND: The diagnosis of prostate cancer (PC) can provide a trigger for dietary change, and there is evidence that healthier diets may improve quality of life and clinical outcomes. However, men's views about dietary change in PC survivorship are largely unknown. This multi-centre qualitative interview study explored men's views about dietary change in PC survivorship, to better understand motivations for, and barriers to, achieving desired changes. The role of radical and active surveillance treatments on dietary change and the influence of men's partners were examined. Focus groups also evaluated stakeholder opinion, including healthcare professionals, about the provision of dietary advice to PC patients. METHODS: A multi-centre interview study explored views about diet and motivations for, and barriers to, dietary change in men at elevated risk or diagnosed with PC following prostate specific antigen (PSA) testing. 58 men and 11 partners were interviewed. Interviews and focus groups were undertaken with 11 healthcare professionals, 5 patients and 4 partners to evaluate stakeholders' opinions about the feasibility and acceptability of providing dietary advice to PC patients. Data were analysed using methods of constant comparison and thematic analysis. RESULTS: Over half of diagnosed men reported making dietary changes, primarily to promote general or prostate health or facilitate coping, despite their uncertainty about diet-PC links. Interest in dietary advice was high. Information needs varied depending on treatment received, with men on active surveillance more frequently modifying their diet and regarding this as an adjunct therapy. Men considered their partners integral to implementing changes. Provision of dietary advice to men diagnosed with PC was considered by healthcare professionals and men to be feasible and appropriate in the context of a holistic 'care package'. CONCLUSIONS: Many men make positive dietary changes after PC diagnosis, which are perceived by men and their partners to bring psychological and general health benefits and could help future dietary intervention trials. Men and their partners desire more and better dietary information that may support PC survivorship, particularly among those embarking on active surveillance/monitoring programmes. There are opportunities for healthcare professionals to support PC patients both clinically and psychologically by the routine integration of healthy eating advice into survivorship care plans.

Genetic variants in the vitamin d receptor are associated with advanced prostate cancer at diagnosis: findings from the prostate testing for cancer and treatment study and a systematic review.

Low levels of plasma vitamin D have been implicated as a possible risk factor for both prostate cancer incidence and advanced disease, and recent phase II trials suggest that vitamin D supplementation might delay progression of prostate cancer. Common polymorphisms in the vitamin D receptor (VDR) are associated with VDR activity and are therefore potentially useful proxies for assessing whether vitamin D is causally related to advanced prostate cancer. We genotyped five well-known VDR polymorphisms in 1,604 men with prostate cancer from the Prostate Testing for Cancer and Treatment study. Our aim was to examine the association between VDR polymorphisms and cancer stage (localized versus advanced) as well as cancer grade (Gleason score <7 versus >or=7). Moreover, we also carried out a systematic review and meta-analysis of 13 similar studies. As a result of our meta-analysis, we revealed three polymorphisms, BsmI, ApaI, and TaqI, associated with high Gleason score with an overall summary odds ratios (95% confidence intervals) of 1.12 (1.00-1.25; bb versus BB + Bb), 1.25 (1.02-1.53; aa versus AA + Aa), and 0.82 (0.69-0.98; Tt + tt versus TT), respectively. The haplotype analysis revealed that the BsmI (B)-ApaI (A)-TaqI (t) participants compared with BsmI (b)-ApaI (a)-TaqI (T) individuals were less likely to have high Gleason scores (odds ratio, 0.84; 95% confidence interval, 0.71-1.00; P(unadjusted) = 0.050; P(adjusted) = 0.014). Our finding provides some support for the hypothesis that low levels of vitamin D may increase the risk of prostate cancer progression.

Inverse relationship between alcohol consumption and active Helicobacter pylori infection: the Bristol Helicobacter project.

OBJECTIVE: The aim of this study was to examine whether smoking or consumption of alcohol or coffee is associated with active Helicobacter pylori (H. pylori) infection. METHODS: This was a cross-sectional population study conducted as part of a randomized controlled trial of H. pylori infection eradication in southwest England. A total of 10,537 subjects, recruited from seven general practices, underwent 13C-urea breath testing for active infection with H. pylori and provided data on smoking, usual weekly consumption of alcohol, and daily intake of coffee. RESULTS: Smoking or coffee consumption were not related to active H. pylori infection. Total alcohol consumption was associated with a small, but not statistically significant, decrease in the odds of infection. After adjustment for age, sex, ethnic status, childhood and adult social class, smoking, coffee consumption, and intake of alcoholic beverages other than wine, subjects drinking 3-6 units of wine/wk had an 11% lower risk of H. pylori infection compared with those who took no wine: OR = 0.89, 95% CI = 0.80-0.99. Higher wine consumption was associated with a further 6% reduction in the risk of infection: OR = 0.83, 95% CI = 0.64-1.07. Intake of 3-6 units of beer (but no greater intake) was associated with a similar reduction in the risk of infection when compared to no beer intake (OR = 0.83, 95% CI = 0.75-0.91). CONCLUSIONS: This study indicates that modest consumption of wine and beer (approximately 7 units/wk) protects against H. pylori infection, presumably by facilitating eradication of the organism.