19 research outputs found

    Associations of the 2018 World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) cancer prevention recommendations with stages of colorectal carcinogenesis

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    Background: While adherence to cancer prevention recommendations is linked to lower risk of colorectal cancer (CRC), few have studied associations across the entire spectrum of colorectal carcinogenesis. Here, we studied the relationship of the standardized 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Score for cancer prevention recommendations with detection of colorectal lesions in a screening setting. As a secondary objective, we examined to what extent the recommendations were being followed in an external cohort of CRC patients. Methods: Adherence to the seven-point 2018 WCRF/AICR Score was measured in screening participants receiving a positive fecal immunochemical test and in CRC patients participating in an intervention study. Dietary intake, body fatness and physical activity were assessed using self-administered questionnaires. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for screen-detected lesions. Results: Of 1486 screening participants, 548 were free from adenomas, 524 had non-advanced adenomas, 349 had advanced lesions and 65 had CRC. Adherence to the 2018 WCRF/AICR Score was inversely associated with advanced lesions; OR 0.82 (95% CI 0.71, 0.94) per score point, but not with CRC. Of the seven individual components included in the score, alcohol, and BMI seemed to be the most influential. Of the 430 CRC patients included in the external cohort, the greatest potential for lifestyle improvement was seen for the recommendations concerning alcohol and red and processed meat, where 10% and 2% fully adhered, respectively. Conclusions: Adherence to the 2018 WCRF/AICR Score was associated with lower probability of screen-detected advanced precancerous lesions, but not CRC. Although some components of the score seemed to be more influential than others (i.e., alcohol and BMI), taking a holistic approach to cancer prevention is likely the best way to prevent the occurrence of precancerous colorectal lesions

    Maternal depression during pregnancy and cord blood DNA methylation: findings from the Avon Longitudinal Study of Parents and Children

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    Up to 13% of women may experience symptoms of depression during pregnancy or in the postpartum period. Depression during pregnancy has been associated with an increased risk of adverse neurodevelopmental outcomes in the child and epigenetic mechanisms could be one of the biological pathways to explain this association. In 844 mother–child pairs from the Avon Longitudinal Study of Parents and Children, we carried out an epigenome-wide association study (EWAS) to investigate associations between prospectively collected data on maternal depression ascertained by the Edinburgh Postnatal Depression Scale in pregnancy and DNA methylation in the cord blood of newborn offspring. In individual site analysis, we identified two CpG sites associated with maternal depression in the middle part of pregnancy. In our regional analysis, we identified 39 differentially methylated regions (DMRs). Seven DMRs were associated with depression at any time point during pregnancy, 7 associated with depression in mid-pregnancy, 23 were associated with depression in late pregnancy, and 2 DMRs were associated with depression throughout pregnancy. Several of these map to genes associated with psychiatric disease and brain development. We attempted replication in The Generation R Study and could not replicate our results. Although our findings in ALSPAC suggest that maternal depression could be associated with cord blood DNA methylation the results should be viewed as preliminary and hypothesis generating until further replicated in a larger sample

    MDM2 antagonist Nutlin-3a potentiates antitumour activity of cytotoxic drugs in sarcoma cell lines

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    <p>Abstract</p> <p>Background</p> <p>Frequent failure and severe side effects of current sarcoma therapy warrants new therapeutic approaches. The small-molecule MDM2 antagonist Nutlin-3a activates the p53 pathway and efficiently induces apoptosis in tumours with amplified <it>MDM2 </it>gene and overexpression of MDM2 protein. However, the majority of human sarcomas have normal level of MDM2 and the therapeutic potential of MDM2 antagonists in this group is still unclear. We have investigated if Nutlin-3a could be employed to augment the response to traditional therapy and/or reduce the genotoxic burden of chemotherapy.</p> <p>Methods</p> <p>A panel of sarcoma cell lines with different <it>TP53 </it>and <it>MDM2 </it>status were treated with Nutlin-3a combined with Doxorubicin, Methotrexate or Cisplatin, and their combination index determined.</p> <p>Results</p> <p>Clear synergism was observed when Doxorubicin and Nutlin-3a were combined in cell lines with wild-type <it>TP53 </it>and amplified <it>MDM2</it>, or with Methotrexate in both <it>MDM2 </it>normal and amplified sarcoma cell lines, allowing for up to tenfold reduction of cytotoxic drug dose. Interestingly, Nutlin-3a seemed to potentiate the effect of classical drugs as Doxorubicin and Cisplatin in cell lines with mutated <it>TP53</it>, but inhibited the effect of Methotrexate.</p> <p>Conclusion</p> <p>The use of Nutlin in combination with classical sarcoma chemotherapy shows promising preclinical potential, but since clear biomarkers are still lacking, clinical trials should be followed up with detailed tumour profiling.</p

    Design of a dietary intervention study in colorectal cancer patients. Evaluation of dietary and physical activity assessment methods in colorectal cancer patients

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    Resultater fra flere studier viser at et kosthold med mye frukt og grønnsaker og begrensede mengder med rødt- og bearbeidet kjøtt kan bidra til å redusere risikoen for å få tarmkreft. I sin avhandling Design of a dietary intervention study in colorectal cancer patients. Evaluation of dietary and physical activity assessment methods in colorectal cancer patients har Hege Berg Henriksen og medarbeidere beskrevet den pågående CRC-NORDIET-studien, som ser på effektene av å følge de norske kostrådene på utvikling av sykdom og overlevelse blant tarmkreftpasienter. Deltakerne blir tilfeldig fordelt i en av to grupper. Den ene gruppen får intensiv oppfølging på kosthold i ett år, mens den andre gruppen følger standard behandling. Begge gruppene får like råd om fysisk aktivitet og alle blir fulgt opp i 15 år. I løpet av denne perioden blir begge gruppene også kartlagt likt både for kosthold, fysisk funksjon og aktivitet, kroppssammensetning, livskvalitet og kroniske sykdommer. Et nytt kort spørreskjema ble laget i denne studien for å kunne si noe om etterlevelsen av de norske kostrådene. Som en del av Hege Berg Henriksen sin avhandling, ble dette skjemaet testet opp mot en kostdagbok blant et utvalg av deltakerne i studien for å se hvorvidt det var i stand til å kunne måle inntak av de ulike matvaregruppene som beskrevet i kostrådene, samt myndighetenes råd om fysisk aktivitet. Det viste seg at spørreskjemaet var i stand til å måle inntak av de fleste matvaregruppene, som frukt, grønnsaker, fisk, meieriprodukter, alkoholholdige drikker, søte drikker, kaffe og til dels kjøtt og fullkornsprodukter. I tillegg var spørreskjemaet i stand til å måle anbefalt mengde fysisk aktivitet og å kunne fange opp de som oppfylte rådene om fysisk aktivitet. Gode verktøy for å kartlegge etterlevelse av kostrådene er viktig for å kunne gi god oppfølging. Vi håper at resultatene fra CRC-NORDIET-studien vil kunne gi et bedre svar på hvilke kostråd vi skal gi tarmkreftpasienter i fremtiden

    A Short Digital Food Frequency Questionnaire (DIGIKOST-FFQ) Assessing Dietary Intake and Other Lifestyle Factors Among Norwegians: Qualitative Evaluation With Focus Group Interviews and Usability Testing

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    BackgroundIn-person dietary counseling and interventions have shown promising results in changing habits toward healthier lifestyles, but they are costly to implement in large populations. Developing digital tools to assess individual dietary intake and lifestyle with integrated personalized feedback systems may help overcome this challenge. We developed a short digital food frequency questionnaire, known as the DIGIKOST-FFQ, to assess diet and other lifestyle factors based on the Norwegian Food-Based Dietary Guidelines. The DIGIKOST-FFQ includes a personalized feedback system, the DIGIKOST report, that benchmarks diet and lifestyle habits. We used qualitative focus group interviews and usability tests to test the feasibility and usability of the DIGIKOST application. ObjectiveWe aimed to explore attitudes, perceptions, and challenges in completing the DIGIKOST-FFQ. We also investigated perceptions and understanding of the personalized feedback in the DIGIKOST report and the technical flow and usability of the DIGIKOST-FFQ and the DIGIKOST report. MethodsHealthy individuals and cancer survivors were invited to participate in the focus group interviews. The transcripts were analyzed using thematic analysis. Another group of healthy individuals completed the usability testing, which was administered individually by a moderator and 2 observers. The results were analyzed based on predefined assignments and discussion with the participants about the interpretation of the DIGIKOST report and technical flow of the DIGIKOST-FFQ. ResultsA total of 20 individuals participated in the focus group interviews, divided into 3 groups of healthy individuals and 3 groups of cancer survivors. Each group consisted of 3 to 4 individuals. Five main themes were investigated: (1) completion time (on average 19.1, SD 8.3, minutes, an acceptable duration), (2) layout (participants reported the DIGIKOST-FFQ was easy to navigate and had clear questions but presented challenges in reporting dietary intake, sedentary time, and physical activity in the last year), (3) questions (the introductory questions on habitual intake worked well), (4) pictures (the pictures were very helpful, but some portion sizes were difficult to differentiate and adding weight in grams would have been helpful), and (5) motivation (users were motivated to obtain personalized feedback). Four individuals participated in the usability testing. The results showed that the users could seamlessly log in, give consent, fill in the DIGIKOST-FFQ, and receive, print, and read the DIGIKOST report. However, parts of the report were perceived as difficult to interpret. ConclusionsThe DIGIKOST-FFQ was overall well received by participants, who found it feasible to use; however, some adjustments with regard to reporting dietary intake and lifestyle habits were suggested. The DIGIKOST report with personalized feedback was the main motivation to complete the questionnaire. The results from the usability testing revealed a need for adjustments and updates to make the report easier to read

    How many days of continuous physical activity monitoring reliably represent time in different intensities in cancer survivors.

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    BACKGROUND: Physical activity (PA) monitoring is applied in a growing number of studies within cancer research. However, no consensus exists on how many days PA should be monitored to obtain reliable estimates in the cancer population. The objective of the present study was to determine the minimum number of monitoring days required for reliable estimates of different PA intensities in cancer survivors when using a six-days protocol. Furthermore, reliability of monitoring days was assessed stratified on sex, age, cancer type, weight status, and educational level. METHODS: Data was obtained from two studies where PA was monitored for seven days using the SenseWear Armband Mini in a total of 984 cancer survivors diagnosed with breast, colorectal or prostate cancer. Participants with ≥22 hours monitor wear-time for six days were included in the reliability analysis (n = 736). The intra-class correlation coefficient (ICC) and the Spearman Brown prophecy formula were used to assess the reliability of different number of monitoring days. RESULTS: For time in light PA, two monitoring days resulted in reliable estimates (ICC &gt;0.80). Participants with BMI ≥25, low-medium education, colorectal cancer, or age ≥60 years required one additional monitoring day. For moderate and moderate-to-vigorous PA, three monitoring days yielded reliable estimates. Participants with BMI ≥25 or breast cancer required one additional monitoring day. Vigorous PA showed the largest within subject variations and reliable estimates were not obtained for the sample as a whole. However, reliable estimates were obtained for breast cancer survivors (4 days), females, BMI ≥30, and age &lt;60 years (6 days). CONCLUSION: Shorter monitoring periods may provide reliable estimates of PA levels in cancer survivors when monitored continuously with a wearable device. This could potentially lower the participant burden and allow for less exclusion of participants not adhering to longer protocols
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