ProDiet: A Phase II Randomized Placebo-controlled Trial of Green Tea Catechins and Lycopene in Men at Increased Risk of Prostate Cancer.

Epidemiologic studies suggest that diet can alter prostate cancer risk. This study aimed to establish the feasibility and acceptability of dietary modification in men at increased risk of prostate cancer. Men were invited with a PSA level of 2.0-2.95 ng/mL or 3.0-19.95 ng/mL with negative prostate biopsies. Randomization (3 × 3 factorial design) to daily green tea and lycopene: green tea drink (3 cups, unblinded) or capsules [blinded, 600 mg flavan-3-ol ()-epigallocatechin-3-gallate (EGCG) or placebo] and lycopene-rich foods (unblinded) or capsules (blinded, 15 mg lycopene or placebo) for 6 months. Primary endpoints were randomization rates and intervention adherence (blinded assessment of metabolites) at 6 months with secondary endpoints of acceptability (from interviews), safety, weight, blood pressure, and PSA. A total of 133 of 469 (28.4%) men approached agreed to be randomized and 132 were followed-up (99.2%). Mean lycopene was 1.28 [95% confidence intervals (CI), 1.09-1.50, P = 0.003] times higher in the lycopene capsule group and 1.42 (95% CI, 1.21-1.66; P < 0.001) times higher in the lycopene-enriched diet group compared with placebo capsules. Median EGCG was 10.7 nmol/L (95% CI, 7.0-32.0) higher in in the active capsule group and 20.0 nmol/L (95% CI, 0.0-19.0) higher in the green tea drink group compared with placebo capsules (both P < 0.001). All interventions were acceptable and well tolerated although men preferred the capsules. Dietary prevention is acceptable to men at risk of prostate cancer. This intervention trial demonstrates that a chemoprevention clinical trial is feasible. Cancer Prev Res; 11(11); 687-96. ©2018 AACR.

Citrus fruits intake and oral cancer risk: A systematic review and meta-analysis.

OBJECTIVE: To quantify the relationship between Citrus intake and risk of cancer of the oral cavity and pharynx. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Ovid MEDLINE, EMBASE, and Web of Science were searched until September 2017. Search terms included Citrus, Citrus aurantifolia, Citrus sinensis, Citrus paradisi, Citrus fruits, Citrus fruits extract, Citrus oil, fruits, oral cancer, mouth cancer, mouth neoplasm. STUDY SELECTION: The selection of studies and the systematic review were carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A pre-defined inclusion checklist resulted in the inclusion of articles which were (i) published in peer-reviewed scientific journals; (ii) English language; (iii) and included a measure of Citrus fruit intake and risk of oral and pharyngeal cancer. Studies were excluded if (i) preparations derived from other fruits were used, (ii) Citrus intake was combined with intake of other fruits; (iii) in vitro or animal models were used. We also excluded reviews, systematic reviews, meta-analyses, letters, personal opinions, conference abstracts and book chapters. DATA EXTRACTION: Three reviewers independently performed the extraction of data from studies included. RESULTS: Seventeen studies met our inclusion criteria and were included in the final review. Pooled analyses showed that those with the highest Citrus fruit intake compared to the lowest intake had a 50% reduction in risk of oral cavity and pharyngeal cancer (OR 0.50; 95% CI 0.43-0.59). CONCLUSION: The studies included in this review and meta-analysis showed an inverse association between Citrus fruit intake and oral cancer.

Non-pharmacological interventions for cognitive impairment due to systemic cancer treatment.

BACKGROUND: It is estimated that up to 75% of cancer survivors may experience cognitive impairment as a result of cancer treatment and given the increasing size of the cancer survivor population, the number of affected people is set to rise considerably in coming years. There is a need, therefore, to identify effective, non-pharmacological interventions for maintaining cognitive function or ameliorating cognitive impairment among people with a previous cancer diagnosis. OBJECTIVES: To evaluate the cognitive effects, non-cognitive effects, duration and safety of non-pharmacological interventions among cancer patients targeted at maintaining cognitive function or ameliorating cognitive impairment as a result of cancer or receipt of systemic cancer treatment (i.e. chemotherapy or hormonal therapies in isolation or combination with other treatments). SEARCH METHODS: We searched the Cochrane Centre Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PUBMED, Cumulative Index of Nursing and Allied Health Literature (CINAHL) and PsycINFO databases. We also searched registries of ongoing trials and grey literature including theses, dissertations and conference proceedings. Searches were conducted for articles published from 1980 to 29 September 2015. SELECTION CRITERIA: Randomised controlled trials (RCTs) of non-pharmacological interventions to improve cognitive impairment or to maintain cognitive functioning among survivors of adult-onset cancers who have completed systemic cancer therapy (in isolation or combination with other treatments) were eligible. Studies among individuals continuing to receive hormonal therapy were included. We excluded interventions targeted at cancer survivors with central nervous system (CNS) tumours or metastases, non-melanoma skin cancer or those who had received cranial radiation or, were from nursing or care home settings. Language restrictions were not applied. DATA COLLECTION AND ANALYSIS: Author pairs independently screened, selected, extracted data and rated the risk of bias of studies. We were unable to conduct planned meta-analyses due to heterogeneity in the type of interventions and outcomes, with the exception of compensatory strategy training interventions for which we pooled data for mental and physical well-being outcomes. We report a narrative synthesis of intervention effectiveness for other outcomes. MAIN RESULTS: Five RCTs describing six interventions (comprising a total of 235 participants) met the eligibility criteria for the review. Two trials of computer-assisted cognitive training interventions (n = 100), two of compensatory strategy training interventions (n = 95), one of meditation (n = 47) and one of physical activity intervention (n = 19) were identified. Each study focused on breast cancer survivors. All five studies were rated as having a high risk of bias. Data for our primary outcome of interest, cognitive function were not amenable to being pooled statistically. Cognitive training demonstrated beneficial effects on objectively assessed cognitive function (including processing speed, executive functions, cognitive flexibility, language, delayed- and immediate- memory), subjectively reported cognitive function and mental well-being. Compensatory strategy training demonstrated improvements on objectively assessed delayed-, immediate- and verbal-memory, self-reported cognitive function and spiritual quality of life (QoL). The meta-analyses of two RCTs (95 participants) did not show a beneficial effect from compensatory strategy training on physical well-being immediately (standardised mean difference (SMD) 0.12, 95% confidence interval (CI) -0.59 to 0.83; I(2)= 67%) or two months post-intervention (SMD - 0.21, 95% CI -0.89 to 0.47; I(2) = 63%) or on mental well-being two months post-intervention (SMD -0.38, 95% CI -1.10 to 0.34; I(2) = 67%). Lower mental well-being immediately post-intervention appeared to be observed in patients who received compensatory strategy training compared to wait-list controls (SMD -0.57, 95% CI -0.98 to -0.16; I(2) = 0%). We assessed the assembled studies using GRADE for physical and mental health outcomes and this evidence was rated to be low quality and, therefore findings should be interpreted with caution. Evidence for physical activity and meditation interventions on cognitive outcomes is unclear. AUTHORS' CONCLUSIONS: Overall, the, albeit low-quality evidence may be interpreted to suggest that non-pharmacological interventions may have the potential to reduce the risk of, or ameliorate, cognitive impairment following systemic cancer treatment. Larger, multi-site studies including an appropriate, active attentional control group, as well as consideration of functional outcomes (e.g. activities of daily living) are required in order to come to firmer conclusions about the benefits or otherwise of this intervention approach. There is also a need to conduct research into cognitive impairment among cancer patient groups other than women with breast cancer.

The Malaysian Breast Cancer Survivorship Cohort (MyBCC): a study protocol.

INTRODUCTION: Over recent decades, the burden of breast cancer has been increasing at an alarming rate in Asia. Prognostic research findings from Western countries may not readily be adapted to Asia, as the outcome of breast cancer depends on a multitude of factors ranging from genetic, clinical and histological predictors, to lifestyle and social predictors. The primary aim of this study is to determine the impact of lifestyle (eg, nutrition, physical activity), mental and sociocultural condition, on the overall survival and quality of life (QoL) among multiethnic Malaysian women following diagnosis of breast cancer. This study aims to advance the evidence on prognostic factors of breast cancer within the Asian setting. The findings may guide management of patients with breast cancer not only during active treatment but also during the survivorship period. METHODS: This hospital-based prospective cohort study will comprise patients with breast cancer (18 years and above), managed in the University Malaya Medical Centre (UMMC). We aim to recruit 1000 cancer survivors over a 6-year period. Data collection will occur at baseline (within 3 months of diagnosis), 6 months, and 1, 3 and 5 years following diagnosis. The primary outcomes are disease-free survival and overall survival, and secondary outcome is QoL. Factors measured are demographic and socioeconomic factors, lifestyle factors (eg, dietary intake, physical activity), anthropometry measurements (eg, height, weight, waist, hip circumference, body fat analysis), psychosocial aspects, and complementary and alternative medicine (CAM) usage. ETHICS AND DISSEMINATION: This protocol was approved by the UMMC Ethical Committee in January 2012. All participants are required to provide written informed consent. The findings from our cohort study will be disseminated via scientific publication as well as presentation to stakeholders including the patients, clinicians, the public and policymakers, via appropriate avenues.

The DietCompLyf study: a prospective cohort study of breast cancer survival and phytoestrogen consumption.

DietCompLyf is a multi-centre prospective study designed to investigate associations between phytoestrogens - naturally occurring plant compounds with oestrogenic properties - and other diet and lifestyle factors with breast cancer recurrence and survival. 3159 women with grades I-III breast cancer were recruited 9-15 months post-diagnosis from 56 UK hospitals. Detailed information on clinico-pathological, diet, lifestyle and quality of life is collected annually up to 5 years. Biological samples have also been collected as a resource for subsequent evaluation. The characteristics of the patients and associations between pre-diagnosis intake of phytoestrogens (isoflavones and lignans; assessed using the EPIC-Norfolk UK 130 question food frequency questionnaire) and breast cancer (i) risk factors and (ii) prognostic factors are described for 1797 women who had complete data for all covariates and phytoestrogens of interest. Isoflavone intakes were higher in the patients who were younger at diagnosis, in the non-smokers, those who had breast-fed and those who took supplements. Lignan intakes were higher in patients with a higher age at diagnosis, in ex-smokers, those who had breast-fed, who took supplements, had a lower BMI at diagnosis, lower age at menarche and were nulliparous. No significant associations between pre-diagnosis phytoestrogen intake and factors associated with improved breast cancer prognosis were observed. The potential for further exploration of the relationship between phytoestrogens and breast cancer recurrence and survival, and for the establishment of evidence to improve dietary and lifestyle advice offered to patients following breast cancer diagnosis using DietCompLyf data is discussed.

Significant changes in dietary intake and supplement use after breast cancer diagnosis in a UK multicentre study.

The diagnosis of cancer can motivate survivors to alter their lifestyle habits. Healthcare providers need to be aware of what changes patients are likely to make in order to derive more pertinent recommendations; however, few studies have reported pre- and post-diagnostic lifestyle behaviours. Semi-quantitative food frequency questionnaires (FFQs) completed approximately 1 year after diagnosis were used to evaluate dietary intake and supplement use before and after diagnosis in a cohort of 1,560 breast cancer patients participating in the UK, prospective DietCompLyf study. Intake of fruit and vegetables, wholegrains and lean sources of protein increased significantly post-diagnosis (P < 0.05, each). Conversely, after diagnosis consumption of high-fat, high-sugar products, red meat, coffee, some alcoholic drinks and refined grains significantly decreased (P < 0.05, each). Post-diagnostic changes in diet were accompanied by changes in the intake of macronutrients and a number of vitamins and minerals. Supplement use was highly prevalent (56.1%) pre-diagnosis, increasing to 62.8% after diagnosis (P = 0.001). Fish oils, multivitamin and minerals, and evening primrose oil were most often used and the proportion of users significantly increased (P < 0.05, each) after diagnosis. The percentage of women using oestrogenic botanical supplements (OBSs) was small but more than doubled to 8.4% after diagnosis (P < 0.05). British women participating in the DietCompLyf study reported significant changes in dietary intake and supplement use after their breast cancer diagnosis. These findings contribute to our understanding of female cancer survivors' dietary behaviours which is crucial for developing and implementing recommendations.

Dietary antioxidant and mineral intake in humans is associated with reduced risk of esophageal adenocarcinoma but not reflux esophagitis or Barrett's esophagus.

The role of antioxidants in the pathogenesis of reflux esophagitis (RE), Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC) remains unknown. We evaluated the associations among dietary antioxidant intake and these diseases. We performed an assessment of dietary antioxidant intake in a case control study of RE (n = 219), BE (n = 220), EAC (n = 224), and matched population controls (n = 256) (the Factors Influencing the Barrett's Adenocarcinoma Relationship study) using a modification of a validated FFQ. We found that overall antioxidant index, a measure of the combined intake of vitamin C, vitamin E, total carotenoids, and selenium, was associated with a reduced risk of EAC [odds ratio (OR) = 0.57; 95% CI = 0.33-0.98], but not BE (OR = 0.95; 95% CI = 0.53-1.71) or RE (OR = 1.60; 95% CI = 0.86-2.98), for those in the highest compared with lowest category of intake. Those in the highest category of vitamin C intake had a lower risk of EAC (OR = 0.37; 95% CI = 0.21-0.66; P-trend = 0.001) and RE (OR = 0.46; 95% CI = 0.24-0.90; P-trend = 0.03) compared with those in the lowest category. Vitamin C intake was not associated with BE, and intake of vitamin E, total carotenoids, zinc, copper, or selenium was not associated with EAC, BE, or RE. In conclusion, the overall antioxidant index was associated with a reduced risk of EAC. Higher dietary intake of vitamin C was associated with a reduced risk of EAC and RE. These results suggest that antioxidants may play a role in the pathogenesis of RE and EAC and may be more important in terms of progression rather than initiation of the disease process.

Do phytoestrogens reduce the risk of breast cancer and breast cancer recurrence? What clinicians need to know.

Oestrogen is an important determinant of breast cancer risk. Oestrogen-mimicking plant compounds called phytoestrogens can bind to oestrogen receptors and exert weak oestrogenic effects. Despite this activity, epidemiological studies suggest that the incidence of breast cancer is lower in countries where the intake of phytoestrogens is high, implying that these compounds may reduce breast cancer risk, and possibly have an impact on survival. Isoflavones and lignans are the most common phytoestrogens in the diet. In this article, we present findings from human observational and intervention studies related to both isoflavone and lignan exposure and breast cancer risk and survival. In addition, the clinical implications of these findings are examined in the light of a growing dietary supplement market. An increasing number of breast cancer patients seek to take supplements together with their standard treatment in the hope that these will either prevent recurrence or treat their menopausal symptoms. Observational studies suggest a protective effect of isoflavones on breast cancer risk and the case may be similar for increasing lignan consumption although evidence so far is inconsistent. In contrast, short-term intervention studies suggest a possible stimulatory effect on breast tissue raising concerns of possible adverse effects in breast cancer patients. However, owing to the dearth of human studies investigating effects on breast cancer recurrence and survival the role of phytoestrogens remains unclear. So far, not enough clear evidence exists on which to base guidelines for clinical use, although raising patient awareness of the uncertain effect of phytoestrogens is recommended.

Acute postprandial effect of hydrogenated fish oil, palm oil and lard on plasma cholesterol, triacylglycerol and non-esterified fatty acid metabolism in normocholesterolaemic males.

The majority of research has focused on the association between trans unsaturated fatty acids (TUFA) from hydrogenated vegetable oils and heart disease even though TUFA are also produced from hydrogenated fish oil. We compared the acute effect of three solid fats on postprandial cholesterol, triacylglycerol (TAG) and NEFA concentrations in normocholesterolaemic males. Eight healthy male volunteers consumed each of the three 40 g fat meals (partially hydrogenated fish oil (PHFO), palm oil and lard) in random order and blood samples were drawn at 2, 4, 6 and 8 h thereafter for lipid analysis. The postprandial response in plasma TAG, TAG-rich lipoprotein-TAG (TRL-TAG), total cholesterol and plasma NEFA, measured as the area under the postprandial curve, was not significantly different between the three meals (P>0.05), which varied in MUFA, PUFA and TUFA content. There was no marked elevation of longer-chain fatty acids (C20-22, cis or trans isomers) into the TRL-TAG fraction following the PHFO meal even though they provided 40 % of the total fatty acids in the PHFO meal. The postprandial TRL-TAG response to PHFO was expected to be higher, as it is higher in TUFA, lower in PUFA and similar in saturated fatty acid composition compared with the lard and palm oil test meals. The absence of a higher postprandial response following ingestion of PHFO could be as a result of reduced absorption and increased oxidation of long-chain fatty acids (both cis and trans isomers).

Development and validation of a food-frequency questionnaire for the determination of detailed fatty acid intakes.

OBJECTIVE: To validate a fat intake questionnaire (FIQ) developed to assess habitual dietary intake while focusing on the assessment of detailed fatty acid intake including total trans unsaturated fatty acids (TUFA). DESIGN: An 88 food item/food group FIQ was developed using a meal pattern technique. Validation was achieved by comparison with dietary intake assessed by a modified diet history (DH) in a cross-over design. Eighty-four individuals supplied adipose tissue biopsies for linoleic acid and total TUFA analysis as an independent validation of the FIQ and DH. SETTING: Medical Centre, Dublin Airport, Republic of Ireland. SUBJECTS: One hundred and five healthy volunteers (43 females and 62 males aged 23-63 years). RESULTS: Significant correlations (P<0.0005) were achieved for intakes of energy (0.78), total fat (0.77), saturated fat (0.77), monounsaturated fat (0.63), polyunsaturated fat (0.73), TUFA (0.67) and linoleic acid (0.71) assessed by the FIQ compared with the DH. Linoleic acid intake assessed by the FIQ and the DH was significantly correlated with adipose tissue concentrations (r=0.58 and 0.49, respectively; P<0.005); however, total TUFA intake was poorly correlated with adipose tissue concentrations (r=0.17 and 0.10 for FIQ and DH, respectively). CONCLUSIONS: The FIQ compared favourably with the DH in assessing habitual diet, in particular fatty acid intake. In addition, the FIQ was successfully validated against the linoleic acid composition of adipose tissue, an independent biomarker of relative fatty acid status. The FIQ could therefore be used as an alternative to the DH as it is a shorter, less labour-intensive method.