Creatine supplementation and resistance training to preserve muscle mass and attenuate cancer progression (CREATINE-52): a protocol for a double-blind randomized controlled trial.

BACKGROUND: Muscle mass is important for metastatic prostate cancer survival and quality of life (QoL). The backbone of treatment for men with metastatic castration sensitive prostate cancer (mCSPC) is androgen deprivation therapy (ADT) with an androgen signaling inhibitor. ADT is an effective cancer treatment, but it facilitates significant declines in muscle mass and adverse health outcomes important to mCSPC survivors, such as fatigue, and reductions in physical function, independence, insulin sensitivity, and QoL. In non-metastatic CSPC survivors, resistance training (RT) preserves muscle mass and improves these related health outcomes, but the biggest barrier to RT in CSPC survivors of all stages is fatigue. Creatine monohydrate supplementation coupled with RT (Cr + RT) may address this barrier since creatine plays a critical role in energy metabolism. Cr + RT in cancer-free older adults and other clinical populations improves muscle mass and related health outcomes. Evidence also suggests that creatine supplementation can complement cancer treatment. Thus, Cr + RT is a strategy that addresses gaps in survivorship needs of people with mCSPC. The purpose of this parallel, double-blind randomized controlled trial is to test the effects of 52-weeks of Cr + RT compared with placebo (PLA) and RT (PLA + RT) on muscle mass, other related health outcomes, and markers of cancer progression. METHODS: We will carry out this trial with our team's established, effective, home-based, telehealth RT program in 200 mCSPC survivors receiving ADT, and evaluate outcomes at baseline, 24-, and 52-weeks. RT will occur twice weekly with elastic resistance bands, and an established creatine supplementation protocol will be used for supplementation delivery. Our approach addresses a major facilitator to RT in mCSPC survivors, a home-based RT program, while utilizing a supervised model for safety. DISCUSSION: Findings will improve delivery of comprehensive survivorship care by providing a multicomponent, patient-centered lifestyle strategy to preserve muscle mass, improve health outcomes, and complement cancer treatment (NCT06112990).

Intake and biomarkers of folate and folic acid as determinants of chemotherapy-induced toxicities in patients with colorectal cancer: a cohort study.

BACKGROUND: Capecitabine is an oral chemotherapeutic drug showing antitumor activity through inhibition of thymidylate synthase, an enzyme involved in folate metabolism. There are concerns about the high intake of certain vitamins, and specifically folate, during chemotherapy with capecitabine. Whether folate or folic acid, the synthetic variant of the vitamin, impact treatment toxicity remains unclear. OBJECTIVE: We studied associations between intake and biomarkers of folate as well as folic acid and toxicities in patients with colorectal cancer (CRC) receiving capecitabine. METHODS: Within the prospective COLON (Colorectal cancer: Longitudinal, Observational study on Nutritional and lifestyle factors that influence recurrence, survival, and quality of life) cohort, 290 patients with stage II to III CRC receiving capecitabine were identified. Dietary and supplemental intake of folate and folic acid were assessed at diagnosis and during chemotherapy using questionnaires (available for 280 patients). Plasma folate and folic acid levels were determined by liquid chromatography tandem mass spectrometry (LC-MS/MS) and were available for 212 patients. Toxicities were defined as toxicity-related modifications of treatment, including dose reductions, regimen switches, and early discontinuation. Associations of intake and biomarkers of folate and folic acid with toxicities were determined using Cox proportional hazards regression adjusted for age and sex. RESULTS: In total, 153 (53%) patients experienced toxicities leading to modification of capecitabine treatment. Folate intake and plasma folate levels were not associated with risk of toxicities. However, use of folic acid-containing supplements during treatment (hazard ratio (HR) 1.81 and 95% confidence interval (CI) 1.15-2.85) and presence of folic acid in plasma at diagnosis (HR 2.09, 95% CI: 1.24, 3.52) and during treatment (HR 2.31, 95% CI: 1.29, 4.13) were associated with an increased risk of toxicities. CONCLUSIONS: This study suggests a potential association between folic acid and capecitabine-induced toxicities, providing a rationale to study diet-drug interactions and raise further awareness of the use of dietary supplements during oncological treatment. CLINICAL TRIAL DETAILS: This trial was registered at clinicaltrials.gov as NCT03191110.

Circulating B-vitamin biomarkers and B-vitamin supplement use in relation to quality of life in patients with colorectal cancer: results from the FOCUS consortium.

BACKGROUND: B vitamins have been associated with the risk and progression of colorectal cancer (CRC), given their central roles in nucleotide synthesis and methylation, yet their association with quality of life in established CRC is unclear. OBJECTIVES: To investigate whether quality of life 6 months postdiagnosis is associated with: 1) circulating concentrations of B vitamins and related biomarkers 6 months postdiagnosis; 2) changes in these concentrations between diagnosis and 6 months postdiagnosis; 3) B-vitamin supplement use 6 months postdiagnosis; and 4) changes in B-vitamin supplement use between diagnosis and 6 months postdiagnosis. METHODS: We included 1676 newly diagnosed stage I-III CRC patients from 3 prospective European cohorts. Circulating concentrations of 9 biomarkers related to the B vitamins folate, riboflavin, vitamin B6, and cobalamin were measured at diagnosis and 6 months postdiagnosis. Information on dietary supplement use was collected at both time points. Health-related quality of life (global quality of life, functioning scales, and fatigue) was assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 6 months postdiagnosis. Confounder-adjusted linear regression analyses were performed, adjusted for multiple testing. RESULTS: Higher pyridoxal 5'-phosphate (PLP) was cross-sectionally associated with better physical, role, and social functioning, as well as reduced fatigue, 6 months postdiagnosis. Associations were observed for a doubling in the hydroxykynurenine ratio [3-hydroxykynurenine: (kynurenic acid + xanthurenic acid + 3-hydroxyanthranilic acid + anthranilic acid); an inverse marker of vitamin B6] and both reduced global quality of life (ß = -3.62; 95% CI: -5.88, -1.36) and worse physical functioning (ß = -5.01; 95% CI: -7.09, -2.94). Dose-response relations were observed for PLP and quality of life. No associations were observed for changes in biomarker concentrations between diagnosis and 6 months. Participants who stopped using B-vitamin supplements after diagnosis reported higher fatigue than nonusers. CONCLUSIONS: Higher vitamin B6 status was associated with better quality of life, yet limited associations were observed for the use of B-vitamin supplements. Vitamin B6 needs further study to clarify its role in relation to quality of life.

Clinically Integrated Physical Therapist Practice in Cancer Care: A New Comprehensive Approach.

Best practice recommendations in cancer care increasingly call for integrated rehabilitation services to address physical impairments and disability. These recommendations have languished primarily due to a lack of pragmatic, generalizable intervention models. This perspective paper proposes a clinically integrated physical therapist (CI-PT) model that enables flexible and scalable services for screening, triage, and intervention addressing functional mobility. The model is based on (1) a CI-PT embedded in cancer care provider clinics, and (2) rehabilitation across the care continuum determined by the patient's level of functional mobility. The CI-PT model includes regular screening of functional mobility in provider clinics via a patient-reported mobility measure-the Activity Measure for Post-Acute Care, a brief physical therapy evaluation tailored to the specific functional needs of the individual-and a tailored, skilled physical therapist intervention based on functional level. The CI-PT model provides a pragmatic, barrier-free, patient-centric, data-driven approach to integrating rehabilitation as part of standard care for survivors of cancer. The model standardizes CI-PT practice and may be sufficiently agile to provide targeted interventions in widely varying cancer settings and populations. Therefore, it may be ideal for wide implementation among outpatient oncological settings. Implementation of this model requires a shared approach to care that includes physical therapists, rehabilitation administrators, cancer care providers, and cancer center administrators.

Bacterial folate biosynthesis and colorectal cancer risk: more than just a gut feeling.

Folate is a B-vitamin with an important role in health and disease. The optimal folate status with regard to human health remains controversial. A low intake of natural folate as well as excessive intake of synthetic folic acid, were previously linked to an increased risk of colorectal cancer or with aberrant molecular pathways related to carcinogenesis in some studies. Importantly, most studies conducted so far, solely focused on dietary intake or circulating levels of folate in relation to cancer risk. Notably, diet or dietary supplements are not the only sources of folate. Several bacteria in the gastrointestinal tract can synthesize B-vitamins, including folate, in quantities that resemble dietary intake. The impact of bacterial folate biosynthesis concerning human health and disease remains unexplored. This review highlights current insights into folate biosynthesis by intestinal bacteria and its implications for processes relevant to cancer development, such as epigenetic DNA modifications and DNA synthesis. Moreover, we will reflect on the emerging question whether food-grade or intestinal bacteria can be considered a potential target to ensure sufficient levels of folate in the gastrointestinal tract and, hence the relevance of bacterial folate biosynthesis for disease prevention or treatment.

Nutraceutical compounds: Echinoids, flavonoids, xanthones and caffeine identified and quantitated in the leaves of Coffea arabica trees from three regions of Brazil.

There are relatively few studies concerning the use of coffee leaves for medicinal purposes and the composition of secondary plant substances. Therefore, we identified and quantitated polyphenolic compounds along with caffeine present in methanol extracts of Coffea arabica leaves from three different regions of Brazil (Ceará, Minas Gerais and São Paulo) by HPLC-ESI-MS. In addition, correlations between polyphenolic content of the coffee leaves and antioxidant assays DPPH, FRAP and ORAC were evaluated. Fifteen compounds belonging to three classes of polyphenols (xanthones, chlorogenic acids and flavonoids) along with the alkaloid caffeine were detected. The mean concentration of total polyphenolic compounds in the leaves of C. arabica, harvested from three different regions of Brazil was quite variable. The highest values were detected in the coffee leaves harvested in Minas Gerais (n = 4) at 40.80(13.00) g/kg (SD), followed by coffee leaves harvested in São Paulo (n = 20) at 24.79(20.19) g/kg, and the lowest in coffee leaves harvested in Ceará (n = 11) in the Northeast of Brazil at 10.30(5.61) g/kg. The three classes of polyphenols, all showed excellent correlations in the antioxidant assays. Coffee leaf tea, appears to be an excellent functional beverage, with its high content of polyphenolic compounds, which may render positive biologic effects, when inbibed as part of the normal human diet.

Cancer survivorship: an integral part of Europe's research agenda.

Cancer survivorship has traditionally received little prioritisation and attention. For a long time, the treatment of cancer has been the main focus of healthcare providers' efforts. It is time to increase the amount of attention given to patients' long-term well-being and their ability to return to a productive and good life. This article describes the current state of knowledge and identifies research areas in need of development to enable interventions for improved survivorship for all cancer patients in Europe. The article is summed up with 11 points in need of further focus.

Seasonal Variations in the Metabolome and Bioactivity Profile of Fucus vesiculosus Extracted by an Optimised, Pressurised Liquid Extraction Protocol.

The metabolism of seaweeds depends on environmental parameters, the availability of nutrients, and biotic/abiotic stresses; therefore, their chemical composition fluctuates throughout the year. This study investigated seasonal variations in the metabolome of the Baltic Sea brown alga Fucus vesiculosus and its potential relation to the bioactivity profile. By using a definitive screening design (DSD) combined with pressurised liquid extraction (PLE), an optimised protocol was developed to extract algal biomass monthly for a full calendar year. An untargeted metabolomics approach using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MSn)-based molecular networking and manual dereplication was employed. The extracts were simultaneously screened for their in vitro antimicrobial, anticancer/apoptotic, and free radical scavenging activities. 44 compounds were putatively dereplicated in the metabolome. Many compounds were found to vary with the sampling month; phlorotannin total ion count (TIC) was highest in summer, whilst chlorophylls, lipids, and carotenoids peaked in winter and spring. The greatest radical scavenging and apoptotic activities against pancreas cancer cells observed in the summer months were attributed to high phlorotannin TIC. Methicillin-resistant Staphylococcus aureus (MRSA) inhibitory activity was produced year-round without a clear seasonal trend. This is the first study applying DSD-based optimised PLE extraction combined with a metabolome analysis of F. vesiculosus for the identification of seasonal variations in both metabolome and bioactivity.

The Evolving Role of Multivitamin/Multimineral Supplement Use among Adults in the Age of Personalized Nutrition.

Micronutrient deficiencies occur in segments of the adult population in the United States. Multivitamin/multimineral supplements (MVMS) are widely used by this population, which reduces inadequacies in micronutrient intake, but the potential for exceeding tolerable upper intake levels in others should be considered. There are concerns associated with the excessive intake of certain nutrients, particularly folic acid, and potential untoward consequences. The advent of nutrigenomics and the enhanced ability to directly study the interactions between nutrition and genetic variants and expression will allow for the conduct of more targeted studies with specific endpoints and may ultimately lead to progress in the field of personalized nutrition. The role of MVMS in health maintenance and chronic disease prevention remains controversial. Conducting studies in this area has been hampered by, among other factors, inconsistent definitions of MVMS, ranging from as few as three vitamins to broad-spectrum products containing more than two dozen vitamins and minerals. Results from some observational studies and large-scale, randomized, controlled trials suggest that MVMS may reduce the risk of some forms of cancer and, potentially, cardiovascular disease. The ongoing COcoa Supplement and Multivitamin Outcomes Study (COSMOS) is expected to build on this research and provide additional insights into these areas.

A systematic review of the interrelation between diet- and surgery-induced weight loss and vitamin D status.

Obesity is a major global health problem and has been associated with vitamin D deficiency. Intentional weight loss may alter vitamin D status and, conversely, vitamin D supplementation has been hypothesized to aid in weight loss. A systematic literature search in PubMed/Medline identified 3173 articles of which 37 studies (randomized controlled trials (RCT) [n=17], non-RCTs [n=20]) are summarized as effect of: (I) diet-induced weight loss on vitamin D status (n=7), (II) vitamin D supplementation on diet-induced weight loss (n=11), (III) surgery-induced weight loss on vitamin D status (n=15), and (IV) vitamin D supplementation after surgery-induced weight loss on vitamin D status (n=5). While all studies on the effect of diet-induced weight loss on vitamin D status have consistently reported increased vitamin D levels, the targeted percentage of weight loss that is necessary for an increase has varied between 5% and >10%. N=11 RCTs testing the effect of vitamin D supplementation observe that vitamin D supplementation does not result in increased weight loss, but may affect body fat loss. Vitamin D deficiency and subsequent hyperparathyroidism have been detected in post-surgery patients, and there is evidence that vitamin D supplementation improves these post-surgery complications. We review the current evidence addressing the role of vitamin D status and supplementation in diet- and surgery-induced weight loss. Subsequently, we highlight gaps in current research and suggest directions for future research including differences in vitamin D supplementation dosages, indoor vs. outdoor exercise, and the assessment of vitamin D status in different body pools.

Characterization and quantitation of the polyphenolic compounds detected in methanol extracts of Pistacia atlantica Desf. fruits from the Guelmim region of Morocco.

High performance liquid chromatography coupled with electrospray ionization mass spectrometry (HPLC-ESI-MS) was used for the identification of the major phenolic compounds in mature P. atlantica fruits from the Guelmim region (southeast of Morocco). In this study twenty seven polyphenolic compounds are identified and quantitated. To date, this is the most comprehensive report on the polyphenolic content of Pistacia fruits. The profiles comprise, three major polyphenolic classes, namely gallates (18.76g/kg; 63.92%), flavonoids (10.12g/kg; 34.48%) and ellagic acid derivatives (0.47g/kg; 1.60%) with a total of 29.35g/kg detected. The major gallate was pentagalloyl glucoside (5.0g/kg; 17.04% of total polyphenolics), the major flavonoid luteolin (3.18g/kg; 10.83% of total polyphenolics) and the major ellagic acid derivative ellagic acid (0.25g/kg; 0.85% of total polyphenolics). Identification of galloyl quinate, digalloyl quinates (x 2), galloyl glucoside, digalloyl glucosides (x 2), trigalloyl glucoside, tetragalloyl glucosides (x 2), pentagalloyl glucoside, 2″-O-galloyl-quercetin-3-O-galactoside, quercetin-3-O-rhamnogalactoside, quercetin-3-O-galactoside, ellagic acid diglucoside, luteolin-4'-O-glucoside, 2″-O-galloyl-luteolin-4'-O-glucoside, quercetin-3-O-glucuronide, kaempferol-3-O-glucoside, eriodictyol, apigenin, ellagic acid diglucoside, ellagic acid glucoside, methyl ellagic acid glucoside, and ellagic acid are described as phytochemical components of Pistacia fruits for the first time.

Comparison of the major polyphenols in mature Argan fruits from two regions of Morocco.

Previous studies have shown that Argan fruits contain a large variety of polyphenolic compounds. Recently, another class of polyphenolic compounds, namely amino phenols have been detected and identified in immature Argan fruits. The objective of this study, was to establish whether or not, these novel compounds are also present in mature Argan fruits. To this end, a comparison was made between mature fruits from two regions of Morocco. Nineteen major compounds were identified and quantitated, including amino phenols, flavonoids, and phenolic acids by chromatographic methods in mature Argan fruits from the two regions of Morocco (Essaouira and Agadir). The phenolic acids were identified as gallic acid and 3,4-dihydroxybenzoic acid; the amino phenols as Arganimide A, and argaminolics A-C, and the flavonoids as rutin pentoside, quercetin-3-O-arabinoside, quercetin glycogallate, quercetin-3-O-rhamnogalactoside, rutin, quercetin-3-O-galactoside (hyperoside), quercetin-3-O-glucoside (quercitrin), quercetin-3-O-arabinoside, quercetin glycohydroxybenzoate, quercetin glycosinapate, quercetin glycoferulate, quercetin glycocoumarate and quercetin. n=145.

SNPs in transporter and metabolizing genes as predictive markers for oxaliplatin treatment in colorectal cancer patients.

Oxaliplatin is frequently used as part of a chemotherapeutic regimen with 5-fluorouracil in the treatment of colorectal cancer (CRC). The cellular availability of oxaliplatin is dependent on metabolic and transporter enzymes. Variants in genes encoding these enzymes may cause variation in response to oxaliplatin and could be potential predictive markers. Therefore, we used a two-step procedure to comprehensively investigate 1,444 single nucleotide polymorphisms (SNPs) from these pathways for their potential as predictive markers for oxaliplatin treatment, using 623 stage II-IV CRC patients (of whom 201 patients received oxaliplatin) from a German prospective patient cohort treated with adjuvant or palliative chemotherapy. First, all genes were screened using the global test that evaluated SNP*oxaliplatin interaction terms per gene. Second, one model was created by backward elimination on all SNP*oxaliplatin interactions of the selected genes. The statistical procedure was evaluated using bootstrap analyses. Nine genes differentially associated with overall survival according to oxaliplatin treatment (unadjusted p values < 0.05) were selected. Model selection resulted in the inclusion of 14 SNPs from eight genes (six transporter genes, ABCA9, ABCB11, ABCC10, ATP1A1, ATP1B2, ATP8B3, and two metabolism genes GSTM5, GRHPR), which significantly improved model fit. Using bootstrap analysis we show an improvement of the prediction error of 3.7% in patients treated with oxaliplatin. Several variants in genes involved in metabolism and transport could thus be potential predictive markers for oxaliplatin treatment in CRC patients. If confirmed, inclusion of these variants in a predictive test could identify patients who are more likely to benefit from treatment with oxaliplatin.

Methylation status at HYAL2 predicts overall and progression-free survival of colon cancer patients under 5-FU chemotherapy.

DNA methylation variations in gene promoter regions are well documented tumor-specific alterations in human malignancies including colon cancer, which may influence tumor behavior and clinical outcome. As a subset of colon cancer patients does not benefit from adjuvant chemotherapy, predictive biomarkers are desirable. Here, we describe that DNA methylation levels at CpG loci of hyaluronoglucosaminidase 2 (HYLA2) could be used to identify stage II and III colon cancer patients who are most likely to benefit from 5-flourouracil (5-FU) chemotherapy with respect to overall survival and progression-free survival.

Physical Exercise Training versus Relaxation in Allogeneic stem cell transplantation (PETRA Study) - Rationale and design of a randomized trial to evaluate a yearlong exercise intervention on overall survival and side-effects after allogeneic stem cell transplantation.

BACKGROUND: Allogeneic stem cell transplantation (allo-HCT) is associated with high treatment-related mortality and innumerable physical and psychosocial complications and side-effects, such as high fatigue levels, loss of physical performance, infections, graft-versus-host disease (GvHD) and distress. This leads to a reduced quality of life, not only during and after transplantation, but also in the long term. Exercise interventions have been shown to be beneficial in allo-HCT patients. However, to date, no study has focused on long-term effects and survival. Previous exercise studies used 'usual care' control groups, leaving it unclear to what extent the observed effects are based on the physical effects of exercise itself, or rather on psychosocial factors such as personal attention. Furthermore, effects of exercise on and severity of GvHD have not been examined so far. We therefore aim to investigate the effects and biological mechanisms of exercise on side-effects, complications and survival in allo-HCT patients during and after transplantation. METHODS/DESIGN: The PETRA study is a randomized, controlled intervention trial investigating the effects of a yearlong partly supervised mixed exercise intervention (endurance and resistance exercises, 3-5 times per week) in 256 patients during and after allogeneic stem cell transplantation. Patients in the control group perform progressive muscle relaxation training (Jacobsen method) with the same frequency. Main inclusion criterion is planned allo-HCT. Main exclusion criteria are increased fracture risk, no walking capability or severe cardiorespiratory problems. Primary endpoint is overall survival after two years; secondary endpoints are non-relapse mortality, median survival, patient reported outcomes including cancer related fatigue and quality of life, physical performance, body composition, haematological/immunological reconstitution, inflammatory parameters, severity of complications and side-effects (e.g. GvHD and infections), and cognitive capacity. DISCUSSION: The PETRA study will contribute to a better understanding of the physiological and psychological effects of exercise training and their biological mechanisms in cancer patients after allo-HCT. The ultimate goal is the implementation of optimized intervention programs to reduce side-effects and improve quality of life and potentially prognosis after allogeneic stem cell transplantation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01374399 .

Pharmacogenetic Analysis of INT 0144 Trial: Association of Polymorphisms with Survival and Toxicity in Rectal Cancer Patients Treated with 5-FU and Radiation.

PURPOSE: We tested whether 18 polymorphisms in 16 genes (GSTP1, COX2, IL10, EGFR, EGF, FGFR4, CCDN1, VEGFR2, VEGF, CXCR2, IL8, MMP3, ICAM1, ERCC1, RAD51, and XRCC3) would predict disease-free survival (DFS), overall survival (OS), and toxicity in the INT0144 trial, which was designed to investigate different postoperative regimens of 5-fluorouracil (5-FU)-based chemoradiation (CRT) in locally advanced rectal cancers: Arm 1 consisted of bolus 5-FU followed by 5-FU protracted venous infusion (PVI) with radiotherapy; arm 2 was induction and concomitant PVI 5-FU with radiotherapy and arm 3 was induction and concomitant bolus 5-FU with radiotherapy. EXPERIMENTAL DESIGN: DNA from 746 stage II/III rectal patients enrolled in the Southwest Oncology Group (SWOG) S9304 phase III trial was analyzed. Genomic DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tumor tissue. The polymorphisms were analyzed using direct DNA-sequencing or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: GSTP1-Ile105Val (rs1695) was significantly associated with DFS and OS and its effect did not vary by treatment arm. The five-year DFS and OS were 53% and 58%, respectively, for G/G, 66% and 72% for G/A, and 57% and 66% for A/A patients. In arm 2, IL8-251A/A genotype (rs4073) was associated with a lower risk of toxicities (P = 0.04). The VEGFR2 H472Q Q/Q genotype (rs1870377) was associated with a higher risk of grade 3-5 proximal upper gastrointestinal tract (PUGIT) mucositis (P = 0.04) in arm 2. However, in arm 1, this genotype was associated with a lower risk of PUGIT mucositis (P = 0.004). CONCLUSION: rs1695 may be prognostic in patients with rectal cancer treated with adjuvant CRT. rs4073 and rs1870377 may exhibit different associations with toxicity, according to the 5-FU schedule.

Pilot walnut intervention study of urolithin bioavailability in human volunteers.

A pilot intervention study was conducted in human volunteers (n = 4) to establish the bioavailability of urolithins, which are the terminal end-products of ellagitannin metabolism by the gastrointestinal microflora. Biospecimens (blood, feces, and urine) along with urolithins purified therefrom were analyzed for their antioxidant capacity in a range of in vitro assays. Urolithin metabolites were identified and quantitated in the biospecimens by negative ion mode HPLC-ESI-MS analysis. The data in this pilot study show that the metabolism of ellagitannins in the four volunteers gave rise to a diverse profile and a highly variable concentration of urolithins in urine. The concentration of glucuronidated urolithins in blood and urine did not correlate with antioxidant capacity. However, the antioxidant capacity of urine, but not plasma biospecimens, was highly correlated with uric acid concentration. The antioxidant capacity of fecal extracts correlated positively with the concentration of urolithin D in both the DPPH and FRAP assays, but not in the ORAC assay, which was entirely consistent with the in vitro assays for pure urolithin D.

No evidence of gene-calcium interactions from genome-wide analysis of colorectal cancer risk.

BACKGROUND: Calcium intake may reduce risk of colorectal cancer, but the mechanisms remain unclear. Studies of interaction between calcium intake and SNPs in calcium-related pathways have yielded inconsistent results. METHODS: To identify gene-calcium interactions, we tested interactions between approximately 2.7 million SNPs across the genome with self-reported calcium intake (from dietary or supplemental sources) in 9,006 colorectal cancer cases and 9,503 controls of European ancestry. To test for multiplicative interactions, we used multivariable logistic regression and defined statistical significance using the conventional genome-wide α = 5E-08. RESULTS: After accounting for multiple comparisons, there were no statistically significant SNP interactions with total, dietary, or supplemental calcium intake. CONCLUSIONS: We found no evidence of SNP interactions with calcium intake for colorectal cancer risk in a large population of 18,509 individuals. IMPACT: These results suggest that in genome-wide analysis common genetic variants do not strongly modify the association between calcium intake and colorectal cancer in European populations.

Polymorphisms in folate-metabolizing enzymes and response to 5-fluorouracil among patients with stage II or III rectal cancer (INT-0144; SWOG 9304).

BACKGROUND: Recurrence and toxicity occur commonly among patients with rectal cancer who are treated with 5-fluorouracil (5-FU). The authors hypothesized that genetic variation in folate-metabolizing genes could play a role in interindividual variability. The objective of the current study was to evaluate the associations between genetic variants in folate-metabolizing genes and clinical outcomes among patients with rectal cancer treated with 5-FU. METHODS: The authors investigated 8 functionally significant polymorphisms in 6 genes (methylenetetrahydrofolate reductase [MTHFR] [C677T, A1298C], SLC19A1 [G80A], SHMT1 [C1420T], dihydrofolate reductase [DHFR] [Del19bp], TS 1494del,and TSER) involved in folate metabolism in 745 patients with TNM stage II or III rectal cancer enrolled in a phase 3 adjuvant clinical trial of 3 regimens of 5-FU and radiotherapy (INT-0144 and SWOG 9304). RESULTS: There were no statistically significant associations noted between polymorphisms in any of the genes and overall survival, disease-free survival (DFS), and toxicity in the overall analyses. Nevertheless, there was a trend toward worse DFS among patients with the variant allele of MTHFR C677T compared with wild-type, particularly in treatment arm 2, in which patients with the MTHFR C677T TT genotype had worse overall survival (hazards ratio, 1.76; 95% confidence interval, 1.06-2.93 [P = .03]) and DFS (hazards ratio, 1.84; 95% confidence interval, 1.12-3.03 [P = .02]) compared with those with homozygous wild-type. In addition, there was a trend toward reduced hematological toxicity among patients with variants of SLC19A1 G80A in treatment arm 1 (P for trend, .06) and reduced esophagitis/stomatitis noted among patients with variants of TSER in treatment arm 3 (P for trend, .06). CONCLUSIONS: Genetic variability in folate-metabolizing enzymes was found to be associated only to a limited degree with clinical outcomes among patients with rectal cancer treated with 5-FU.

Counseling patients on cancer diets: a review of the literature and recommendations for clinical practice.

BACKGROUND: Many cancer patients use cancer diets. MATERIALS AND METHODS: We listed 13 cancer diets simulating an internet search for which we systematically reviewed clinical data. In the next step we derived recommendations on counseling patients using a Delphi process. RESULTS: We evaluated the following diets: raw vegetables and fruits, alkaline diet, macrobiotics, Gerson's regime, Budwig's and low carbohydrate or ketogenic diet. We did not find clinical evidence supporting any of the diets. Furthermore, case reports and pre-clinical data point to the potential harm of some of these diets. From published recommendations on counseling on complementary and alternative medicine, we were able to derive 14 recommendations for counseling on cancer diets. CONCLUSION: Considering the lack of evidence of benefits from cancer diets and potential harm by malnutrition, oncologists should engage more in counseling cancer patients on such diets. Our recommendations could be helpful in this process.