Publications by authors named "Eline H van Roekel"

37 Publications

Longitudinal associations of fiber, vegetable, and fruit intake with quality of life and fatigue in colorectal cancer survivors up to 24 months post-treatment.

Am J Clin Nutr 2021 Oct 23. Epub 2021 Oct 23.

Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands.

Background: The increasing colorectal cancer (CRC) survivor population highlights the need for dietary recommendations in order to enhance health-related quality of life (HRQoL) and alleviate symptoms of fatigue, chemotherapy-induced peripheral neuropathy (CIPN) and gastro-intestinal problems.

Objectives: Because of the therapeutic potential of dietary fiber on the gut, we aim to assess longitudinal associations of post-diagnostic dietary fiber, fruit and vegetable intake, a major source of dietary fiber, with HRQoL, fatigue, CIPN and gastro-intestinal symptoms in CRC survivors from 6 weeks to 24 months post-treatment.

Methods: In a prospective cohort among stage I-III CRC survivors (n = 459), five repeated study measurements between diagnosis and 24 months post-treatment were executed. Dietary fiber and fruit and vegetable intake were measured by 7-day dietary records. HRQoL, fatigue, CIPN and gastro-intestinal symptoms were measured by validated questionnaires. We applied confounder-adjusted linear mixed-models to analyze longitudinal associations from 6 weeks until 24 months post-treatment, and used hybrid models to disentangle the overall association into intra-individual changes and inter-individual differences over time.

Results: Higher dietary fiber intake, fruit and vegetable intake were longitudinally associated with statistically significant better physical functioning and less fatigue. Intra-individual analyses showed that an increase of 10 g/d in dietary fiber within individuals over time was associated with better physical functioning (β: 2.3; 95% CI: 0.1, 4.4), role functioning (ability to perform daily activities - 5.9; 1.5, 10.3), and less fatigue (-4.1; -7.7,-0.5). An average increase in fruit and vegetable intake of 100 g/d between individuals over time was predominantly associated with less fatigue (-2.2; -4.2,-0.3). No associations were found with CIPN and gastro-intestinal symptoms.

Conclusion: Our results suggest that increasing dietary fiber, fruit and vegetable intake is related to better physical and role functioning and less fatigue in the first two years after the end of treatment for CRC.Registration: The EnCoRe study was registered at trialregister.nl as NL6904 (former ID: NTR7099).
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http://dx.doi.org/10.1093/ajcn/nqab360DOI Listing
October 2021

Linking Physical Activity to Breast Cancer: Text Mining Results and a Protocol for Systematically Reviewing Three Potential Mechanistic Pathways.

Cancer Epidemiol Biomarkers Prev 2022 Jan 20;31(1):11-15. Epub 2021 Oct 20.

Bristol Medical School, University of Bristol, Bristol, United Kingdom.

Epidemiologic research suggests that physical activity is associated with a reduced risk of breast cancer, but the causal nature of this link is not clear. Investigating mechanistic pathways can provide evidence of biological plausibility and improve causal inference. This project will examine three putative pathways (sex steroid hormones, insulin signaling, and inflammation) in a series of two-stage systematic reviews. Stage 1 used Text Mining for Mechanism Prioritisation (TeMMPo) to identify and prioritize relevant biological intermediates. Stage 2 will systematically review the findings from studies of (i) physical activity and intermediates and (ii) intermediates and breast cancer. Ovid MEDLINE, EMBASE, and SPORTDiscus will be searched using a combination of subject headings and free-text terms. Human intervention and prospective, observational studies will be eligible for inclusion. Meta-analysis will be performed where possible. Risk of bias will be assessed using the Cochrane Collaboration tool, or the ROBINS-I or ROBINS-E tool, depending on study type. Strength of evidence will be assessed using the GRADE system. In addition to synthesizing the mechanistic evidence that links physical activity with breast cancer risk, this project may also identify priority areas for future research and help inform the design and implementation of physical activity interventions..
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http://dx.doi.org/10.1158/1055-9965.EPI-21-0435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8755571PMC
January 2022

Linking Physical Activity to Breast Cancer via Sex Steroid Hormones, Part 2: The Effect of Sex Steroid Hormones on Breast Cancer Risk.

Cancer Epidemiol Biomarkers Prev 2022 Jan 20;31(1):28-37. Epub 2021 Oct 20.

Cancer Epidemiology Division, Cancer Council Victoria, Victoria, Australia.

We undertook a systematic review and appraised the evidence for an effect of circulating sex steroid hormones and sex hormone-binding globulin (SHBG) on breast cancer risk in pre- and postmenopausal women. Systematic searches identified prospective studies relevant to this review. Meta-analyses estimated breast cancer risk for women with the highest compared with the lowest level of sex hormones, and the DRMETA Stata package was used to graphically represent the shape of these associations. The ROBINS-E tool assessed risk of bias, and the GRADE system appraised the strength of evidence. In premenopausal women, there was little evidence that estrogens, progesterone, or SHBG were associated with breast cancer risk, whereas androgens showed a positive association. In postmenopausal women, higher estrogens and androgens were associated with an increase in breast cancer risk, whereas higher SHBG was inversely associated with risk. The strength of the evidence quality ranged from low to high for each hormone. Dose-response relationships between sex steroid hormone concentrations and breast cancer risk were most notable for postmenopausal women. These data support the plausibility of a role for sex steroid hormones in mediating the causal relationship between physical activity and the risk of breast cancer..
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http://dx.doi.org/10.1158/1055-9965.EPI-21-0438DOI Listing
January 2022

Linking Physical Activity to Breast Cancer via Sex Hormones, Part 1: The Effect of Physical Activity on Sex Steroid Hormones.

Cancer Epidemiol Biomarkers Prev 2022 Jan 20;31(1):16-27. Epub 2021 Oct 20.

Cancer Epidemiology Division, Cancer Council Victoria, Victoria, Australia.

The effect of physical activity on breast cancer risk may be partly mediated by sex steroid hormones. This review synthesized and appraised the evidence for an effect of physical activity on sex steroid hormones. Systematic searches were performed using MEDLINE (Ovid), EMBASE (Ovid), and SPORTDiscus to identify experimental studies and prospective cohort studies that examined physical activity and estrogens, progestins, and/or androgens, as well as sex hormone binding globulin (SHBG) and glucocorticoids in pre- and postmenopausal women. Meta-analyses were performed to generate effect estimates. Risk of bias was assessed, and the GRADE system was used to appraise quality of the evidence. Twenty-eight randomized controlled trials (RCT), 81 nonrandomized interventions, and six observational studies were included. Estrogens, progesterone, and androgens mostly decreased, and SHBG increased, in response to physical activity. Effect sizes were small, and evidence quality was graded moderate or high for each outcome. Reductions in select sex steroid hormones following exercise supports the biological plausibility of the first part of the physical activity-sex hormone-breast cancer pathway. The confirmed effect of physical activity on decreasing circulating sex steroid hormones supports its causal role in preventing breast cancer..
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http://dx.doi.org/10.1158/1055-9965.EPI-21-0437DOI Listing
January 2022

The burden of colorectal cancer survivors in the Netherlands: costs, utilities, and associated patient characteristics.

J Cancer Surviv 2021 Sep 11. Epub 2021 Sep 11.

Department of Health Services Research, CAPHRI Care and Public Health Research Institute, Maastricht University, Maastricht, The Netherlands.

Purpose: The aim of this study is to assess the societal burden of colorectal cancer (CRC) survivorship 2-10 years post-diagnosis in terms of (1) societal costs, and (2) quality of life/utilities, and to analyze associated patient characteristics.

Methods: This is a cross-sectional, bottom-up prevalence-based burden of disease study, conducted from a societal perspective in the Netherlands. In total, 155 CRC survivors were included. Utilities were measured by the EQ-5D-5L, using the Dutch tariffs. A cost questionnaire was developed to obtain cost information. Subgroup analyses were performed, based on patient characteristics and sensitivity analyses.

Results: Of all CRC survivors, 81(54%) reported no problems for mobility, 133(88%) for self-care, 98(65%) for daily activities, 59(39%) for pain/discomfort, and 112(74%) for anxiety/depression on the EQ-5D-5L. The average EQ-5D-5L utility score was 0.82 (SD = 0.2) on a scale from 0 (death) to 1 (perfect health). Significant differences in utility score were found for gender, tumor stage, number of comorbidities, and lifestyle score. The average societal costs per CRC survivor per 6 months were estimated at €971 (min = €0, max = €32,425). Significant differences in costs were found for the number of comorbidities.

Conclusions: This study shows a considerable burden of CRC survivors 2-10 years after diagnosis, in comparison with survivors sooner after diagnosis and with healthy individuals in the Netherlands.

Implications For Cancer Survivors: Long-term care of CRC survivors should focus on improving the societal burden by identifying modifiable factors, as summarized in the WCRF/AICR lifestyle score, including body composition, physical activity, and diet.
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http://dx.doi.org/10.1007/s11764-021-01096-6DOI Listing
September 2021

Longitudinal associations of physical activity with plasma metabolites among colorectal cancer survivors up to 2 years after treatment.

Sci Rep 2021 07 2;11(1):13738. Epub 2021 Jul 2.

Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.

We investigated longitudinal associations of moderate-to-vigorous physical activity (MVPA) and light-intensity physical activity (LPA) with plasma concentrations of 138 metabolites after colorectal cancer (CRC) treatment. Self-reported physical activity data and blood samples were obtained at 6 weeks, and 6, 12 and 24 months post-treatment in stage I-III CRC survivors (n = 252). Metabolite concentrations were measured by tandem mass spectrometry (BIOCRATES AbsoluteIDQp180 kit). Linear mixed models were used to evaluate confounder-adjusted longitudinal associations. Inter-individual (between-participant differences) and intra-individual associations (within-participant changes over time) were assessed as percentage difference in metabolite concentration per 5 h/week of MVPA or LPA. At 6 weeks post-treatment, participants reported a median of 6.5 h/week of MVPA (interquartile range:2.3,13.5) and 7.5 h/week of LPA (2.0,15.8). Inter-individual associations were observed with more MVPA being related (FDR-adjusted q-value < 0.05) to higher concentrations of arginine, citrulline and histidine, eight lysophosphatidylcholines, nine diacylphosphatidylcholines, 13 acyl-alkylphosphatidylcholines, two sphingomyelins, and acylcarnitine C10:1. No intra-individual associations were found. LPA was not associated with any metabolite. More MVPA was associated with higher concentrations of several lipids and three amino acids, which have been linked to anti-inflammatory processes and improved metabolic health. Mechanistic studies are needed to investigate whether these metabolites may affect prognosis.
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http://dx.doi.org/10.1038/s41598-021-92279-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253824PMC
July 2021

Circulating tryptophan metabolites and risk of colon cancer: Results from case-control and prospective cohort studies.

Int J Cancer 2021 11 12;149(9):1659-1669. Epub 2021 Jul 12.

International Agency for Research on Cancer, Lyon, France.

Dysregulation of tryptophan metabolism has been linked to colorectal tumorigenesis; however, epidemiological studies investigating tryptophan metabolites in relation to colorectal cancer risk are limited. We studied associations of plasma tryptophan, serotonin and kynurenine with colon cancer risk in two studies with cancer patients and controls, and in one prospective cohort: ColoCare Study (110 patients/153 controls), the Colorectal Cancer Study of Austria (CORSA; 46 patients/390 controls) and the European Prospective Investigation into Cancer and Nutrition (EPIC; 456 matched case-control pairs). Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for colon cancer risk. Tryptophan was inversely associated with colon cancer risk in ColoCare (OR per 1-SD = 0.44; 95% CI, 0.31-0.64) and EPIC (OR per 1-SD = 0.86; 95% CI, 0.74-0.99). Comparing detectable vs nondetectable levels, serotonin was positively associated with colon cancer in CORSA (OR = 6.39; 95% CI, 3.61-11.3) and EPIC (OR = 2.03; 95% CI, 1.20-3.40). Kynurenine was inversely associated with colon cancer in ColoCare (OR per 1-SD = 0.74; 95% CI, 0.55-0.98), positively associated in CORSA (OR per 1-SD = 1.79; 95% CI, 1.27-2.52), while no association was observed in EPIC. The kynurenine-to-tryptophan ratio was positively associated with colon cancer in ColoCare (OR per 1-SD = 1.38; 95% CI, 1.03-1.84) and CORSA (OR per 1-SD = 1.44; 95% CI, 1.06-1.96), but not in EPIC. These results suggest that higher plasma tryptophan may be associated with lower colon cancer risk, while increased serotonin may be associated with a higher risk of colon cancer. The kynurenine-to-tryptophan ratio may also reflect altered tryptophan catabolism during colon cancer development.
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http://dx.doi.org/10.1002/ijc.33725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429124PMC
November 2021

Increases in adipose tissue and muscle function are longitudinally associated with better quality of life in colorectal cancer survivors.

Sci Rep 2021 06 14;11(1):12440. Epub 2021 Jun 14.

Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, P.O. BOX 616, 6200 MD, Maastricht, The Netherlands.

Colorectal cancer (CRC) survivors need evidence-based guidelines pertaining to post-treatment body composition, which could benefit health-related quality of life (HRQoL). We aimed to describe the course of several body composition measures, and to assess longitudinal associations of these measures with HRQoL, fatigue and chemotherapy-induced peripheral neuropathy (CIPN). In a prospective cohort among stage I-III CRC survivors (n = 459), five repeated home visits from diagnosis up to 24 months post-treatment were executed. Body mass index (BMI), waist circumference and fat percentage were assessed as measures of adiposity, and muscle arm circumference and handgrip strength as measures of muscle mass and function. We applied linear mixed-models to describe changes in body composition over time and to analyze overall longitudinal associations. Of included participants, 44% was overweight and 31% was obese at diagnosis. All body composition measures followed similar trends, decreasing from diagnosis to 6 weeks and then increasing up to 24 months post-treatment. In confounder-adjusted mixed models, increases in adipose tissue and muscle function were longitudinally associated with better HRQoL and less fatigue, regardless of pre-treatment body composition. With regards to improving HRQoL, decreasing fatigue and CIPN, clinical practice should also focus on restoring body tissues after CRC treatment.Trial registration: NTR7099.
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http://dx.doi.org/10.1038/s41598-021-91709-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203762PMC
June 2021

Longitudinal Associations of Sedentary Behavior and Physical Activity with Quality of Life in Colorectal Cancer Survivors.

Med Sci Sports Exerc 2021 11;53(11):2298-2308

Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, THE NETHERLANDS.

Introduction: Given the growing population of colorectal cancer (CRC) survivors, identifying ways to enhance health-related quality of life (HRQoL) and alleviate complaints of fatigue and chemotherapy-induced peripheral neuropathy (CIPN) is essential.

Purpose: We aimed to assess longitudinal associations of sedentary behavior (SB) and moderate to vigorous physical activity (MVPA) independently, as well as their joint association, with HRQoL, fatigue, and CIPN in CRC survivors.

Methods: In a prospective cohort among stage I-stage III CRC survivors (n = 396), five repeated home visits from diagnosis up to 24 months posttreatment were executed. SB was measured using triaxial accelerometers, and MVPA, HRQoL, fatigue, and CIPN were measured by validated questionnaires. We applied confounder-adjusted linear mixed models to analyze longitudinal associations from 6 wk until 24 months posttreatment.

Results: Average time in prolonged SB (accumulated in bouts of duration ≥30 min) was 5.3 ± 2.7 h·d-1, and approximately 82% of survivors were classified as sufficiently active (≥150 min·wk-1 of MVPA) at 6 wk posttreatment. Decreases in SB and increases in MVPA were independently associated with better HRQoL and less fatigue over time. No associations were found for CIPN complaints. A synergistic interaction was observed between prolonged SB and MVPA in affecting functioning scales. Relative to CRC survivors with low prolonged SB and high MVPA, survivors with high prolonged SB and low MVPA reported a stronger decrease in physical functioning and role functioning over time than expected based on the independent associations of prolonged SB and MVPA.

Conclusion: Our longitudinal results show that less SB and more MVPA are beneficial for CRC survivors' HRQoL and fatigue levels. Our findings regarding interaction underscore that joint recommendations to avoid prolonged sitting and accumulate MVPA are important.
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http://dx.doi.org/10.1249/MSS.0000000000002703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8542069PMC
November 2021

Metabolic signatures of greater body size and their associations with risk of colorectal and endometrial cancers in the European Prospective Investigation into Cancer and Nutrition.

BMC Med 2021 04 30;19(1):101. Epub 2021 Apr 30.

International Agency for Research on Cancer, World Health Organization, Lyon, France.

Background: The mechanisms underlying the obesity-cancer relationship are incompletely understood. This study aimed to characterise metabolic signatures of greater body size and to investigate their association with two obesity-related malignancies, endometrial and colorectal cancers, and with weight loss within the context of an intervention study.

Methods: Targeted mass spectrometry metabolomics data from 4326 participants enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and 17 individuals from a single-arm pilot weight loss intervention (Intercept) were used in this analysis. Metabolic signatures of body size were first determined in discovery (N = 3029) and replication (N = 1297) sets among EPIC participants by testing the associations between 129 metabolites and body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) using linear regression models followed by partial least squares analyses. Conditional logistic regression models assessed the associations between the metabolic signatures with endometrial (N = 635 cases and 648 controls) and colorectal (N = 423 cases and 423 controls) cancer risk using nested case-control studies in EPIC. Pearson correlation between changes in the metabolic signatures and weight loss was tested among Intercept participants.

Results: After adjustment for multiple comparisons, greater BMI, WC, and WHR were associated with higher levels of valine, isoleucine, glutamate, PC aa C38:3, and PC aa C38:4 and with lower levels of asparagine, glutamine, glycine, serine, lysoPC C17:0, lysoPC C18:1, lysoPC C18:2, PC aa C42:0, PC ae C34:3, PC ae C40:5, and PC ae C42:5. The metabolic signature of BMI (OR 1.50, 95% CI 1.30-1.74), WC (OR 1.46, 95% CI 1.27-1.69), and WHR (OR 1.54, 95% CI 1.33-1.79) were each associated with endometrial cancer risk. Risk of colorectal cancer was positively associated with the metabolic signature of WHR (OR: 1.26, 95% CI 1.07-1.49). In the Intercept study, a positive correlation was observed between weight loss and changes in the metabolic signatures of BMI (r = 0.5, 95% CI 0.06-0.94, p = 0.03), WC (r = 0.5, 95% CI 0.05-0.94, p = 0.03), and WHR (r = 0.6, 95% CI 0.32-0.87, p = 0.01).

Conclusions: Obesity is associated with a distinct metabolic signature comprising changes in levels of specific amino acids and lipids which is positively associated with both colorectal and endometrial cancer and is potentially reversible following weight loss.
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http://dx.doi.org/10.1186/s12916-021-01970-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086283PMC
April 2021

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.

Am J Clin Nutr 2021 06;113(6):1468-1481

Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.

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 (β = -3.62; 95% CI: -5.88, -1.36) and worse physical functioning (β = -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.
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http://dx.doi.org/10.1093/ajcn/nqaa422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168355PMC
June 2021

Circulating Folate and Folic Acid Concentrations: Associations With Colorectal Cancer Recurrence and Survival.

JNCI Cancer Spectr 2020 Oct 7;4(5):pkaa051. Epub 2020 Jul 7.

Department of Surgery, Hospital Group Twente ZGT, Almelo, the Netherlands.

Background: Folates, including folic acid, may play a dual role in colorectal cancer development. Folate is suggested to be protective in early carcinogenesis but could accelerate growth of premalignant lesions or micrometastases. Whether circulating concentrations of folate and folic acid, measured around time of diagnosis, are associated with recurrence and survival in colorectal cancer patients is largely unknown.

Methods: Circulating concentrations of folate, folic acid, and folate catabolites p-aminobenzoylglutamate and p-acetamidobenzoylglutamate were measured by liquid chromatography-tandem mass spectrometry at diagnosis in 2024 stage I-III colorectal cancer patients from European and US patient cohort studies. Multivariable-adjusted Cox proportional hazard models were used to assess associations between folate, folic acid, and folate catabolites concentrations with recurrence, overall survival, and disease-free survival.

Results: No statistically significant associations were observed between folate, p-aminobenzoylglutamate, and p-acetamidobenzoylglutamate concentrations and recurrence, overall survival, and disease-free survival, with hazard ratios ranging from 0.92 to 1.16. The detection of folic acid in the circulation (yes or no) was not associated with any outcome. However, among patients with detectable folic acid concentrations (n = 296), a higher risk of recurrence was observed for each twofold increase in folic acid (hazard ratio = 1.31, 95% confidence interval = 1.02 to 1.58). No statistically significant associations were found between folic acid concentrations and overall and disease-free survival.

Conclusions: Circulating folate and folate catabolite concentrations at colorectal cancer diagnosis were not associated with recurrence and survival. However, caution is warranted for high blood concentrations of folic acid because they may increase the risk of colorectal cancer recurrence.
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http://dx.doi.org/10.1093/jncics/pkaa051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583160PMC
October 2020

Associations of the dietary World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) recommendations with patient-reported outcomes in colorectal cancer survivors 2-10 years post-diagnosis: a cross-sectional analysis.

Br J Nutr 2021 05 22;125(10):1188-1200. Epub 2020 Oct 22.

Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, 6200 MD Maastricht, the Netherlands.

The World Cancer Research Fund and American Institute for Cancer Research (WCRF/AICR) advise cancer survivors to follow their lifestyle recommendations for cancer prevention. Adhering to these recommendations may have beneficial effects on patient-reported outcomes after a cancer diagnosis, but evidence is scarce. We aimed to assess associations of the individual dietary WCRF/AICR recommendations regarding fruit and vegetables, fibre, fast foods, red and processed meat, sugar-sweetened drinks and alcohol consumption with patient-reported outcomes in colorectal cancer (CRC) survivors. Cross-sectional data of 150 stage I-III CRC survivors, 2-10 years post-diagnosis, were used. Dietary intake was measured by 7-d dietary records. Validated questionnaires were used to measure health-related quality of life (HRQoL), fatigue and neuropathy. Confounder-adjusted linear regression models were used to analyse associations of each WCRF/AICR dietary recommendation with patient-reported outcomes. Higher vegetable intake (per 50 g) was associated with better global QoL (β 2·6; 95 % CI 0·6, 4·7), better physical functioning (3·3; 1·2, 5·5) and lower levels of fatigue (-4·5; -7·6, -1·4). Higher fruit and vegetables intake (per 100 g) was associated with better physical functioning (3·2; 0·8, 5·5) and higher intake of energy-dense food (per 100 kJ/100 g) with worse physical functioning (-4·2; -7·1, -1·2). No associations of dietary recommendations with neuropathy were found. These findings suggest that adhering to specific dietary WCRF/AICR recommendations is associated with better HRQoL and less fatigue in CRC survivors. Although the recommendations regarding healthy dietary habits may be beneficial for the well-being of CRC survivors, longitudinal research is warranted to gain insight into the direction of associations.
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http://dx.doi.org/10.1017/S0007114520003487DOI Listing
May 2021

Impact of Pre-blood Collection Factors on Plasma Metabolomic Profiles.

Metabolites 2020 May 21;10(5). Epub 2020 May 21.

Population Sciences, Huntsman Cancer Institute, Salt Lake City, UT 84112, USA.

Demographic, lifestyle and biospecimen-related factors at the time of blood collection can influence metabolite levels in epidemiological studies. Identifying the major influences on metabolite concentrations is critical to designing appropriate sample collection protocols and considering covariate adjustment in metabolomics analyses. We examined the association of age, sex, and other short-term pre-blood collection factors (time of day, season, fasting duration, physical activity, NSAID use, smoking and alcohol consumption in the days prior to collection) with 133 targeted plasma metabolites (acylcarnitines, amino acids, biogenic amines, sphingolipids, glycerophospholipids, and hexoses) among 108 individuals that reported exposures within 48 h before collection. The differences in mean metabolite concentrations were assessed between groups based on pre-collection factors using two-sided -tests and ANOVA with FDR correction. Percent differences in metabolite concentrations were negligible across season, time of day of collection, fasting status or lifestyle behaviors at the time of collection, including physical activity or the use of tobacco, alcohol or NSAIDs. The metabolites differed in concentration between the age and sex categories for 21.8% and 14.3% metabolites, respectively. In conclusion, extrinsic factors in the short period prior to collection were not meaningfully associated with concentrations of selected endogenous metabolites in a cross-sectional sample, though metabolite concentrations differed by age and sex. Larger studies with more coverage of the human metabolome are warranted.
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http://dx.doi.org/10.3390/metabo10050213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281389PMC
May 2020

Higher Serum Vitamin D Concentrations Are Longitudinally Associated with Better Global Quality of Life and Less Fatigue in Colorectal Cancer Survivors up to 2 Years after Treatment.

Cancer Epidemiol Biomarkers Prev 2020 06 3;29(6):1135-1144. Epub 2020 Apr 3.

Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands.

Background: Vitamin D status may be an important determinant of health-related quality of life of colorectal cancer survivors. The current study investigated longitudinal associations between serum 25-hydroxyvitamin D (25OHD) concentrations and quality of life in stage I-III colorectal cancer survivors up to 2 years after treatment.

Methods: Patients with colorectal cancer ( = 261) were included upon diagnosis. Home visits (including blood sampling) were performed at diagnosis and at 6 weeks, 6 months, 1 year, and 2 years after treatment. Serum 25OHD concentrations were measured using LC/MS-MS and adjusted for season. Validated questionnaires were used to assess global quality of life and cognitive functioning (EORTC-QLQ-C30), fatigue (EORTC-QLQ-C30 and Checklist Individual Strength, CIS), and depression and anxiety (Hospital Anxiety and Depression Scale). Statistical analyses were performed using linear mixed models and adjusted for sex, age, time since diagnosis, therapy, comorbidities, physical activity, and body mass index.

Results: At diagnosis, 45% of patients were vitamin D deficient (<50 nmol/L). After treatment, 25OHD concentrations increased on average with 3.1 nmol/L every 6 months. In confounder-adjusted models, 20 nmol/L increments in 25OHD were longitudinally associated with increased global quality of life [β 2.9; 95% confidence interval (CI), 1.5-4.3] and reduced fatigue (EORTC-QLQ-C30 subscale: β -3.5; 95% CI, -5.3 to -1.8 and CIS: β -2.8; 95% CI, -4.7 to -0.9). Observed associations were present both within and between individuals over time.

Conclusions: Higher concentrations of 25OHD were longitudinally associated with better global quality of life and less fatigue in colorectal cancer survivors.

Impact: This study suggests that higher 25OHD concentrations may be beneficial for colorectal cancer survivors. Future intervention studies are needed to corroborate these findings.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-1522DOI Listing
June 2020

One-carbon metabolites, B vitamins and associations with systemic inflammation and angiogenesis biomarkers among colorectal cancer patients: results from the ColoCare Study.

Br J Nutr 2020 05 5;123(10):1187-1200. Epub 2020 Feb 5.

Division of Cancer Control and Population Sciences, Huntsman Cancer Institute, Salt Lake City, UT, USA.

B vitamins involved in one-carbon metabolism have been implicated in the development of inflammation- and angiogenesis-related chronic diseases, such as colorectal cancer (CRC). Yet, the role of one-carbon metabolism in inflammation and angiogenesis among CRC patients remains unclear. The objective of this study was to investigate associations of components of one-carbon metabolism with inflammation and angiogenesis biomarkers among newly diagnosed CRC patients (n 238) in the prospective ColoCare Study, Heidelberg. We cross-sectionally analysed associations between twelve B vitamins and one-carbon metabolites and ten inflammation and angiogenesis biomarkers from pre-surgery serum samples using multivariable linear regression models. We further explored associations among novel biomarkers in these pathways with Spearman partial correlation analyses. We hypothesised that pyridoxal-5'-phosphate (PLP) is inversely associated with inflammatory biomarkers. We observed that PLP was inversely associated with C-reactive protein (CRP) (r -0·33, Plinear < 0·0001), serum amyloid A (SAA) (r -0·23, Plinear = 0·003), IL-6 (r -0·39, Plinear < 0·0001), IL-8 (r -0·20, Plinear = 0·02) and TNFα (r -0·12, Plinear = 0·045). Similar findings were observed for 5-methyl-tetrahydrofolate and CRP (r -0·14), SAA (r -0·14) and TNFα (r -0·15) among CRC patients. Folate catabolite acetyl-para-aminobenzoylglutamic acid (pABG) was positively correlated with IL-6 (r 0·27, Plinear < 0·0001), and pABG was positively correlated with IL-8 (r 0·21, Plinear < 0·0001), indicating higher folate utilisation during inflammation. Our data support the hypothesis of inverse associations between PLP and inflammatory biomarkers among CRC patients. A better understanding of the role and inter-relation of PLP and other one-carbon metabolites with inflammatory processes among colorectal carcinogenesis and prognosis could identify targets for future dietary guidance for CRC patients.
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http://dx.doi.org/10.1017/S0007114520000422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425811PMC
May 2020

Chemotherapy and vitamin D supplement use are determinants of serum 25-hydroxyvitamin D levels during the first six months after colorectal cancer diagnosis.

J Steroid Biochem Mol Biol 2020 05 7;199:105577. Epub 2020 Jan 7.

Division of Human Nutrition and Health, Wageningen University and Research, Wageningen, the Netherlands.

Vitamin D metabolites, including 25-hydroxyvitamin D (25(OH)D), may inhibit colorectal cancer (CRC) progression. Here we investigated cross-sectional and longitudinal associations of demographic, lifestyle and clinical characteristics with 25(OH)D serum concentrations in CRC patients at diagnosis and six months later. In 1201 newly-diagnosed stage I-III CRC patients, 25(OH)D levels were analysed twice. Multivariable linear regression was used to assess demographic, lifestyle and clinical determinants of 25(OH)D levels at diagnosis and six months later. Linear mixed models were used to assess characteristics associated with changes in 25(OH)D levels over time. Results of our study showed that vitamin D intake from diet or supplements, use of calcium supplements, BMI and disease stage were associated with 25(OH)D levels at both time points. Six months after diagnosis, gender and having received chemo- and/or radiotherapy were also associated with 25(OH)D levels. A stronger decrease in 25(OH)D levels was observed in patients who underwent chemotherapy, compared to surgery only (β-6.9 nmol/L 95 %CI -9.8; -4.0). Levels of 25(OH)D levels increased in patients using vitamin D supplements compared to non-users (β 4.0 nmol/L 95 %CI 1.2; 6.8). In conclusion, vitamin D supplement use and treatment appear to be important determinants of 25(OH)D levels during the first six months after CRC diagnosis, although the difference in 25(OH)D levels was minor. ClinicalTrials.gov Identifier: NCT03191110.
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http://dx.doi.org/10.1016/j.jsbmb.2020.105577DOI Listing
May 2020

Evaluating the Validity of a Food Frequency Questionnaire in Comparison with a 7-Day Dietary Record for Measuring Dietary Intake in a Population of Survivors of Colorectal Cancer.

J Acad Nutr Diet 2020 02 3;120(2):245-257. Epub 2019 Dec 3.

Background: Food frequency questionnaires (FFQs) are a commonly used method to assess dietary intake in epidemiological studies. It is important to evaluate the validity of FFQs in the population of interest.

Objective: To evaluate the validity of an FFQ for measuring dietary intake in survivors of colorectal cancer (CRC), relative to a 7-day dietary record.

Design: Dietary intake was assessed 1 year after the end of CRC treatment. Participants first completed a 7-day dietary record and 2 weeks later a 253-item FFQ that measured intake in the preceding month.

Participants/setting: Data were used from a subsample of participants (n=100) enrolled in an ongoing prospective study (EnCoRe study) in the Netherlands, from 2015 to 2018.

Main Outcome Measures: Estimated intakes of total energy, 19 nutrients, and 20 food groups as well as scoring adherence to the dietary recommendations of the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) were compared between both dietary assessment methods.

Statistical Analyses Performed: Means and standard deviations, Spearman rank correlations corrected for within-person variation and total energy, and κ agreement between quintiles were assessed.

Results: The median Spearman correlation corrected for within-person variation for nutrients and total energy was 0.60. Correlations >0.50 were found for 15 of 19 nutrients, with highest agreement for vitamin B-12 (0.74), polysaccharides (0.75), and alcohol (0.91). On average, 73% (range=60% to 84%) of participants were classified into the exact same or adjacent nutrient quintile. The median Spearman correlation corrected for within-person variation for food groups was 0.62. Correlations >0.50 were found for 17 of 20 food groups, with highest agreement for cereals and cereal products (0.96), fish (0.96), and potatoes (0.99). The Spearman correlation between total scores of the WCRF/AICR dietary recommendations was 0.53.

Conclusions: Relative to a 7-day dietary record, the validity of an FFQ for measuring dietary intake among survivors of CRC appeared moderate to good for most nutrients and food groups.
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http://dx.doi.org/10.1016/j.jand.2019.09.008DOI Listing
February 2020

Sedentary Behavior and Chronic Disease: Mechanisms and Future Directions.

J Phys Act Health 2020 01 1;17(1):52-61. Epub 2020 Jan 1.

Background: Recent updates to physical activity guidelines highlight the importance of reducing sedentary time. However, at present, only general recommendations are possible (ie, "Sit less, move more"). There remains a need to investigate the strength, temporality, specificity, and dose-response nature of sedentary behavior associations with chronic disease, along with potential underlying mechanisms.

Methods: Stemming from a recent research workshop organized by the Sedentary Behavior Council themed "Sedentary behaviour mechanisms-biological and behavioural pathways linking sitting to adverse health outcomes," this paper (1) discusses existing challenges and scientific discussions within this advancing area of science, (2) highlights and discusses emerging areas of interest, and (3) points to potential future directions.

Results: A brief knowledge update is provided, reflecting upon current and evolving thinking/discussions, and the rapid accumulation of new evidence linking sedentary behavior to chronic disease. Research "action points" are made at the end of each section-spanning from measurement systems and analytic methods, genetic epidemiology, causal mediation, and experimental studies to biological and behavioral determinants and mechanisms.

Conclusion: A better understanding of whether and how sedentary behavior is causally related to chronic disease will allow for more meaningful conclusions in the future and assist in refining clinical and public health policies/recommendations.
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http://dx.doi.org/10.1123/jpah.2019-0377DOI Listing
January 2020

Plasma metabolites associated with colorectal cancer stage: Findings from an international consortium.

Int J Cancer 2020 06 10;146(12):3256-3266. Epub 2019 Oct 10.

Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany.

Colorectal cancer is the second most common cause of cancer-related death globally, with marked differences in prognosis by disease stage at diagnosis. We studied circulating metabolites in relation to disease stage to improve the understanding of metabolic pathways related to colorectal cancer progression. We investigated plasma concentrations of 130 metabolites among 744 Stages I-IV colorectal cancer patients from ongoing cohort studies. Plasma samples, collected at diagnosis, were analyzed with liquid chromatography-mass spectrometry using the Biocrates AbsoluteIDQ™ p180 kit. We assessed associations between metabolite concentrations and stage using multinomial and multivariable logistic regression models. Analyses were adjusted for potential confounders as well as multiple testing using false discovery rate (FDR) correction. Patients presented with 23, 28, 39 and 10% of Stages I-IV disease, respectively. Concentrations of sphingomyelin C26:0 were lower in Stage III patients compared to Stage I patients (p  < 0.05). Concentrations of sphingomyelin C18:0 and phosphatidylcholine (diacyl) C32:0 were statistically significantly higher, while citrulline, histidine, phosphatidylcholine (diacyl) C34:4, phosphatidylcholine (acyl-alkyl) C40:1 and lysophosphatidylcholines (acyl) C16:0 and C17:0 concentrations were lower in Stage IV compared to Stage I patients (p  < 0.05). Our results suggest that metabolic pathways involving among others citrulline and histidine, implicated previously in colorectal cancer development, may also be linked to colorectal cancer progression.
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http://dx.doi.org/10.1002/ijc.32666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216900PMC
June 2020

Metabolomics Analytics Workflow for Epidemiological Research: Perspectives from the Consortium of Metabolomics Studies (COMETS).

Metabolites 2019 Jul 17;9(7). Epub 2019 Jul 17.

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.

The application of metabolomics technology to epidemiological studies is emerging as a new approach to elucidate disease etiology and for biomarker discovery. However, analysis of metabolomics data is complex and there is an urgent need for the standardization of analysis workflow and reporting of study findings. To inform the development of such guidelines, we conducted a survey of 47 cohort representatives from the Consortium of Metabolomics Studies (COMETS) to gain insights into the current strategies and procedures used for analyzing metabolomics data in epidemiological studies worldwide. The results indicated a variety of applied analytical strategies, from biospecimen and data pre-processing and quality control to statistical analysis and reporting of study findings. These strategies included methods commonly used within the metabolomics community and applied in epidemiological research, as well as novel approaches to pre-processing pipelines and data analysis. To help with these discrepancies, we propose use of open-source initiatives such as the online web-based tool COMETS Analytics, which includes helpful tools to guide analytical workflow and the standardized reporting of findings from metabolomics analyses within epidemiological studies. Ultimately, this will improve the quality of statistical analyses, research findings, and study reproducibility.
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http://dx.doi.org/10.3390/metabo9070145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6681081PMC
July 2019

Metabolomics in epidemiologic research: challenges and opportunities for early-career epidemiologists.

Metabolomics 2019 01 7;15(1). Epub 2019 Jan 7.

Epidemiology and Genomics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Bethesda, USA.

Background: The application of metabolomics to epidemiologic studies is increasing.

Aim Of Review: Here, we describe the challenges and opportunities facing early-career epidemiologists aiming to apply metabolomics to their research.

Key Scientific Concepts Of Review: Many challenges inherent to metabolomics may provide early-career epidemiologists with the opportunity to play a pivotal role in answering critical methodological questions and moving the field forward. Although generating large-scale high-quality metabolomics data can be challenging, data can be accessed through public databases, collaboration with senior researchers or participation within interest groups. Such efforts may also assist with obtaining funding, provide knowledge on training resources, and help early-career epidemiologists to publish in the field of metabolomics.
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http://dx.doi.org/10.1007/s11306-018-1468-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844759PMC
January 2019

Is dietary supplement use longitudinally associated with fatigue in stage I-III colorectal cancer survivors?

Clin Nutr 2020 01 29;39(1):234-241. Epub 2019 Jan 29.

Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, PO Box 616, 6200 MD, Maastricht, the Netherlands. Electronic address:

Background & Aims: Supplement use among colorectal cancer (CRC) survivors is common, yet evidence supporting its beneficial health effects is mostly lacking and cancer-specific lifestyle guidelines advise against the use of supplements. We aimed to describe the use of supplements by CRC survivors from diagnosis to 2 years post-treatment and investigate how overall supplement use is longitudinally associated with fatigue.

Methods: In a prospective cohort study of stage I-III CRC survivors (n = 325), information on supplement use was collected during repeated home visits at diagnosis and at 6 weeks, 6, 12, and 24 months post-treatment. Fatigue was assessed using the Checklist Individual Strength (score range 20-140) at all post-treatment time points. Linear mixed-models were applied to analyze longitudinal associations of overall supplement use with fatigue, adjusted for sex, age, comorbidities, chemotherapy, and physical activity.

Results: At all time points, about 40% of participants used supplements. Multivitamins/multiminerals were the most frequently used supplements at all time points. Of participants with at least two available measurements, 28% were consistent users, 45% consistent nonusers, and 27% inconsistent users (i.e. reported both use and nonuse). Reported fatigue levels declined significantly after treatment. Overall, no statistically significant differences in fatigue score over time were observed between supplement users and nonusers. Likewise, no intra-individual associations of supplement use and fatigue were found. However, in inter-individual analyses, supplement users reported to experience more fatigue compared to nonusers (β 7.0, 95% CI 0.3; 13.7).

Conclusions: No overall association between supplement use and fatigue was found. Results of the current study do therefore not imply that supplement use alleviates complaints of fatigue among CRC survivors. However, increased levels of fatigue may be a reason for supplement use among CRC survivors.
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http://dx.doi.org/10.1016/j.clnu.2018.12.037DOI Listing
January 2020

Physical Activity, Television Viewing Time, and DNA Methylation in Peripheral Blood.

Med Sci Sports Exerc 2019 03;51(3):490-498

Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, AUSTRALIA.

Introduction: Physical activity may affect health via DNA methylation. The epigenetic influences of sedentary behaviors such as television viewing are unknown. We performed a genomewide study of DNA methylation in peripheral blood in relation to physical activity and television viewing time.

Methods: DNA methylation was measured using the Illumina Infinium HumanMethylation450K BeadChip array in blood samples collected at baseline (N = 5513) and follow-up (N = 1249) from participants in the Melbourne Collaborative Cohort Study. At baseline, times per week of leisure-time physical activity were self-reported. At follow-up, the International Physical Activity Questionnaire was used to assess MET-hours per week of total and leisure-time physical activity and hours per day of television viewing time. Linear mixed models were used to assess associations between physical activity and television viewing measures and DNA methylation at individual CpG sites, adjusted for potential confounders and batch effects.

Results: At follow-up, total physical activity was associated with DNA methylation at cg10266336 (P = 6.0 × 10), annotated to the SAA2 gene. Weaker evidence of associations (P < 1.0 × 10) were observed for an additional 14 CpG sites with total physical activity, for 7 CpG sites with leisure-time physical activity, and for 9 CpG sites with television viewing time. Changes in leisure-time physical activity between baseline and follow-up were associated with methylation changes (P < 0.05) at four of the seven CpG sites with weaker evidence of cross-sectional associations with leisure-time physical activity.

Conclusion: Physical activity and television viewing may be associated with blood DNA methylation, a potential pathway to chronic disease development. Further research using accelerometer data and larger sample sizes is warranted.
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http://dx.doi.org/10.1249/MSS.0000000000001827DOI Listing
March 2019

Letter by Yang et al Regarding Article, "Accelerometer-Measured Physical Activity and Sedentary Behavior in Relation to All-Cause Mortality: The Women's Health Study".

Circulation 2018 07;138(1):114-115

Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, Australia (Y.Y., B.M.L., E.H.v.R.).

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http://dx.doi.org/10.1161/CIRCULATIONAHA.117.032789DOI Listing
July 2018

Circulating Metabolites Associated with Alcohol Intake in the European Prospective Investigation into Cancer and Nutrition Cohort.

Nutrients 2018 May 22;10(5). Epub 2018 May 22.

Danish Cancer Society Research Center, 2100 Copenhagen, Denmark.

Identifying the metabolites associated with alcohol consumption may provide insights into the metabolic pathways through which alcohol may affect human health. We studied associations of alcohol consumption with circulating concentrations of 123 metabolites among 2974 healthy participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Alcohol consumption at recruitment was self-reported through dietary questionnaires. Metabolite concentrations were measured by tandem mass spectrometry (BIOCRATES AbsoluteIDQTM p180 kit). Data were randomly divided into discovery (2/3) and replication (1/3) sets. Multivariable linear regression models were used to evaluate confounder-adjusted associations of alcohol consumption with metabolite concentrations. Metabolites significantly related to alcohol intake in the discovery set (FDR -value < 0.05) were further tested in the replication set (Bonferroni-corrected -value < 0.05). Of the 72 metabolites significantly related to alcohol intake in the discovery set, 34 were also significant in the replication analysis, including three acylcarnitines, the amino acid citrulline, four lysophosphatidylcholines, 13 diacylphosphatidylcholines, seven acyl-alkylphosphatidylcholines, and six sphingomyelins. Our results confirmed earlier findings that alcohol consumption was associated with several lipid metabolites, and possibly also with specific acylcarnitines and amino acids. This provides further leads for future research studies aiming at elucidating the mechanisms underlying the effects of alcohol in relation to morbid conditions.
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http://dx.doi.org/10.3390/nu10050654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5986533PMC
May 2018

Colorectal cancers survivors' adherence to lifestyle recommendations and cross-sectional associations with health-related quality of life.

Br J Nutr 2018 07 16;120(2):188-197. Epub 2018 Apr 16.

1Department of Epidemiology,GROW - School for Oncology and Developmental Biology,Maastricht University,PO Box 616,6200 MD Maastricht,The Netherlands.

The lifestyle recommendations of the World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) are primarily intended for cancer prevention. In the absence of specific recommendations for cancer survivors, we investigated adherence of colorectal cancer (CRC) survivors to the WCRF/AICR lifestyle recommendations and associations with health-related quality of life (HRQoL). The cross-sectional part of the Energy for life after ColoRectal cancer (EnCoRe) study was conducted in 155 CRC survivors (stage I-III), 2-10 years post diagnosis. Dietary intake, physical activity and general body fatness were measured by 7-d food diaries, by questionnaires and accelerometers and BMI, respectively. Adherence to each of the ten WCRF/AICR recommendations was scored as 0 (no/low adherence), 0·5 (moderate adherence) or 1 point (complete adherence), and summed into an overall adherence score (range: 0-10). HRQoL, disability and distress were assessed by validated questionnaires. Associations of the overall WCRF/AICR adherence score with HRQoL outcomes were analysed by confounder-adjusted linear regression. The mean adherence score was 5·1 (sd 1·4, range: 1·5-8·5). In confounder-adjusted models, a higher adherence score was significantly associated with the HRQoL dimension better physical functioning (β per 1 point difference in score: 2·6; 95 % CI 0·2, 5·1) and with less fatigue (β: -3·3; 95 % CI -6·4, -0·1). In conclusion, higher adherence of CRC survivors to WCRF/AICR lifestyle recommendations for cancer prevention was associated with better physical functioning and with less fatigue. This study adds to the limited knowledge on adherence to lifestyle behaviours in CRC survivors and relationships with quality of life. Prospective studies are needed to investigate longitudinal associations.
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http://dx.doi.org/10.1017/S0007114518000661DOI Listing
July 2018

A Comparative Study on the WCRF International/University of Bristol Methodology for Systematic Reviews of Mechanisms Underpinning Exposure-Cancer Associations.

Cancer Epidemiol Biomarkers Prev 2017 11 28;26(11):1583-1594. Epub 2017 Jul 28.

Division of Cancer Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, Germany.

The World Cancer Research Fund (WCRF) International and the University of Bristol have developed a novel framework for providing an overview of mechanistic pathways and conducting a systematic literature review of the biologically plausible mechanisms underlying exposure-cancer associations. Two teams independently applied the two-stage framework on mechanisms underpinning the association between body fatness and breast cancer to test the framework feasibility and reproducibility as part of a WCRF-commissioned validation study. In stage I, a "hypothesis-free" approach was used to provide an overview of potential intermediate mechanisms between body fatness and breast cancer. Dissimilar rankings of potential mechanisms were observed between the two teams due to different applications of the framework. In stage II, a systematic review was conducted on the insulin-like growth factor 1 receptor () chosen as an intermediate mechanism. Although the studies included differed, both teams found inconclusive evidence for the body fatness- association and modest evidence linking to breast cancer, and therefore concluded that there is currently weak evidence for as mechanism linking body fatness to breast cancer. The framework is a good starting point for conducting systematic reviews by integrating evidence from mechanistic studies on exposure-cancer associations. On the basis of our experience, we provide recommendations for future users. .
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http://dx.doi.org/10.1158/1055-9965.EPI-17-0230DOI Listing
November 2017

Associations of adipose and muscle tissue parameters at colorectal cancer diagnosis with long-term health-related quality of life.

Qual Life Res 2017 07 17;26(7):1745-1759. Epub 2017 Mar 17.

Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.

Purpose: Increased visceral adiposity (visceral obesity) and muscle wasting (sarcopenia) at colorectal cancer (CRC) diagnosis, quantified by computed tomography (CT) image analysis, have been unfavorably associated with short-term clinical outcomes and survival, but associations with long-term health-related quality of life (HRQoL) have not been investigated. We studied associations of visceral adiposity, muscle fat infiltration, muscle mass, and sarcopenia at CRC diagnosis with HRQoL 2-10 years post-diagnosis.

Methods: A cross-sectional study was conducted in 104 stage I‒III CRC survivors, diagnosed at Maastricht University Medical Center+, the Netherlands (2002-2010). Diagnostic CT images at the level of the third lumbar vertebra were analyzed to retrospectively determine visceral adipose tissue area (cm); intermuscular adipose tissue area (cm) and mean muscle attenuation (Hounsfield units) as measures of muscle fat infiltration; and skeletal muscle index (SMI, cm/m) as measure of muscle mass and for determining sarcopenia.

Results: Participants showed a large variation in body composition parameters at CRC diagnosis with a mean visceral adipose tissue area of 136.1 cm (standard deviation: 93.4) and SMI of 47.8 cm/m (7.2); 47% was classified as being viscerally obese, and 32% as sarcopenic. In multivariable linear regression models, associations of the body composition parameters with long-term global quality of life, physical, role and social functioning, disability, fatigue, and distress were not significant, and observed mean differences were below predefined minimal important differences.

Conclusions: Although visceral obesity and sarcopenia are relatively common at CRC diagnosis, we found no significant associations of these parameters with long-term HRQoL in stage I-III CRC survivors.
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http://dx.doi.org/10.1007/s11136-017-1539-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5486890PMC
July 2017

Associations of sedentary time and patterns of sedentary time accumulation with health-related quality of life in colorectal cancer survivors.

Prev Med Rep 2016 Dec 1;4:262-9. Epub 2016 Jul 1.

Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.

Sedentary behavior (sitting/lying at low energy expenditure while awake) is emerging as an important risk factor that may compromise the health-related quality of life (HRQoL) of colorectal cancer (CRC) survivors. We examined associations of sedentary time with HRQoL in CRC survivors, 2-10 years post-diagnosis. In a cross-sectional study, stage I-III CRC survivors (n = 145) diagnosed (2002-2010) at Maastricht University Medical Center+, the Netherlands, wore the thigh-mounted MOX activity monitor 24 h/day for seven consecutive days. HRQoL outcomes were assessed by validated questionnaires (EORTC QLQ-C30, WHODAS II, Checklist Individual Strength, and Hospital Anxiety and Depression Scale). Confounder-adjusted linear regression models were used to estimate associations with HRQoL outcomes of MOX-derived total and prolonged sedentary time (in prolonged sedentary bouts ≥ 30 min), and usual sedentary bout duration, corrected for waking wear time. On average, participants spent 10.2 h/day sedentary (SD, 1.6), and 4.5 h/day in prolonged sedentary time (2.3). Mean usual sedentary bout duration was 27.3 min (SD, 16.8). Greater total and prolonged sedentary time, and longer usual sedentary bout duration were associated with significantly (P < 0.05) lower physical functioning, and higher disability and fatigue scores. Greater prolonged sedentary time and longer usual sedentary bout duration also showed significant associations with lower global quality of life and role functioning. Associations with distress and social functioning were non-significant. Sedentary time was cross-sectionally associated with poorer HRQoL outcomes in CRC survivors. Prospective studies are needed to investigate whether sedentary time reduction is a potential target for lifestyle interventions aiming to improve the HRQoL of CRC survivors.
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http://dx.doi.org/10.1016/j.pmedr.2016.06.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941044PMC
December 2016
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