Publications by authors named "Martijn J L Bours"

51 Publications

Longitudinal Associations of Adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Lifestyle Recommendations with Quality of Life and Symptoms in Colorectal Cancer Survivors up to 24 Months Post-Treatment.

Cancers (Basel) 2022 Jan 14;14(2). Epub 2022 Jan 14.

Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, 6211 LK Maastricht, The Netherlands.

Post-treatment adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) lifestyle recommendations were associated with health-related quality of life (HRQoL), fatigue, and chemotherapy-induced peripheral neuropathy (CIPN) in colorectal cancer (CRC) survivors. In a prospective cohort among CRC survivors ( = 459), repeated home-visits were performed at 6 weeks, 6, 12, and 24 months post-treatment. Dietary intake, body composition, sedentary behaviour, and physical activity were assessed to construct a lifestyle score based on adherence to seven 2018 WCRF/AICR recommendations. Longitudinal associations of the lifestyle score with HRQoL, fatigue, and CIPN were analysed by confounder-adjusted linear mixed models. A higher lifestyle score was associated with better physical functioning and less activity-related fatigue, but not with CIPN. Adjustment for physical activity substantially attenuated observed associations, indicating its importance in the lifestyle score with regards to HRQoL. In contrast, adjustment for body composition and alcohol inflated observed associations, indicating that both recommendations had a counteractive influence within the lifestyle score. Our findings suggest that CRC survivors benefit from an overall adherence to the WCRF/AICR lifestyle recommendations in terms of HRQoL and fatigue, but not CIPN. Specific recommendations have a varying influence on these associations, complicating the interpretation and requiring further study.
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http://dx.doi.org/10.3390/cancers14020417DOI Listing
January 2022

Cross-Sectional Associations between Dietary Daily Nicotinamide Intake and Patient-Reported Outcomes in Colorectal Cancer Survivors, 2 to 10 Years Post-Diagnosis.

Nutrients 2021 Oct 21;13(11). Epub 2021 Oct 21.

Department of Pharmacology and Toxicology, Maastricht University, 6200 MD Maastricht, The Netherlands.

Supplementation with nicotinamide adenine dinucleotide (NAD) precursors including dietary nicotinamide has been found to boost tissue NAD levels and ameliorate oxidative stress-induced damage that contributes to aging and aging-related diseases. The association between dietary NAD precursors and patient-reported health-related outcomes in cancer survivors has not been investigated. This study aimed to determine associations of dietary nicotinamide intake with different patient-reported outcomes in colorectal cancer survivors, 2 to 10 years post-diagnosis. A total of 145 eligible participants were recruited into this cross-sectional study. Dietary nicotinamide intake level was calculated based on data from 7-day food diaries. Fatigue was assessed with the Checklist Individual Strength (CIS), which is a subscale of the cancer-specific European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC), and anxiety and depression were assessed with Hospital Anxiety and Depression Scale (HADS). Oxidative stress marker serum protein carbonyl contents and serum NAD levels were measured. A hierarchical linear regression model with confounder adjustment was performed to analyze the association of nicotinamide intake, serum protein carbonyl contents, and NAD levels with patient-reported outcomes. The median values of daily nicotinamide intake for male and female participants were 19.1 and 14.4 mg, respectively. Daily dietary nicotinamide intake was associated with a lower level of fatigue (β: -14.85 (-28.14, -1.56)) and a lower level of anxiety and depression (β: -4.69 (-8.55, -0.83)). Subgroup analyses by sex showed that a beneficial association between nicotinamide intake and patient-reported outcomes was mainly found in men. To conclude, our findings suggested that higher dietary NAD precursor nicotinamide intake was cross-sectionally associated with less patient-reported outcomes in CRC survivors.
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http://dx.doi.org/10.3390/nu13113707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8624000PMC
October 2021

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

Associations between alcohol consumption and anxiety, depression, and health-related quality of life in colorectal cancer survivors.

J Cancer Surviv 2021 Sep 16. Epub 2021 Sep 16.

Center of Research on Psychological disorders and Somatic diseases, Tilburg University, PO Box 90153, 5000 LE, Tilburg, The Netherlands.

Purpose: Alcohol consumption is a major risk factor for colorectal cancer (CRC). It is currently poorly understood, however, how alcohol and different alcoholic beverage types are related to psychosocial outcomes in CRC survivors.

Methods: We used data of N = 910 CRC survivors from the pooled EnCoRe and PROCORE cohorts and harmonized them into five time points: at diagnosis and 3, 6, 12, and 24 months post-diagnosis. Generalized estimated equation models were used to examine longitudinal associations of alcohol consumption, including consumption of beer, wine, and liquor, with anxiety, depression, and health-related quality of life (HRQoL), while correcting for sociodemographic, lifestyle, and clinical factors.

Results: Survivors were on average 67 years and 37% was female. In the first 2 years post-diagnosis, survivors who consumed more alcoholic drinks/week reported lower anxiety and depressive symptoms and better HRQoL on all domains and symptom scales. This was the case for moderate and heavy amounts of alcohol and mostly for consuming beer and wine, but not for liquor. Associations were more often significant for men and for younger persons (< 67 years at baseline).

Conclusions: Generally, alcohol consumption was observed to be longitudinally related to less anxiety and depression and better HRQoL in CRC survivors.

Implications For Cancer Survivors: Although alcohol consumption is generally unfavorable due to increased risk of carcinogenesis and worse prognosis after CRC, it seems to be associated with better psychosocial outcomes in the first 2 years after diagnosis and treatment. More research is needed to gain knowledge about reasons for drinking and causality.
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http://dx.doi.org/10.1007/s11764-021-01090-yDOI Listing
September 2021

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

Is sleep associated with BMI, waist circumference, and diet among long-term colorectal cancer survivors? Results from the population-based PROFILES registry.

Support Care Cancer 2021 Dec 6;29(12):7225-7235. Epub 2021 Jul 6.

The Netherlands Comprehensive Cancer Organisation, Utrecht, The Netherlands.

Purpose: In the general population, poor sleep quality and short sleep duration are associated with a higher body mass index (BMI) and waist circumference (WC), and an unhealthy diet. The aim of this study was to assess if the association between sleep quality and duration and BMI, WC, and diet quality also exists among colorectal cancer (CRC) survivors, as many CRC survivors have an unhealthy weight and diet.

Methods: Cross-sectional data from a longitudinal CRC cohort were used. In this study, survivors were 4-13 years post diagnosis. The Pittsburgh Sleep Quality Index (PSQI) was used to assess both sleep quality and sleep duration. Diet quality was assessed by scoring adherence (low, moderate, high) to the 2007 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) recommendations of five food groups and nutrients: fruit and vegetables, dietary fiber, red and processed meat, alcoholic beverages, and sugary drinks, using a brief diet screener. BMI and WC were self-measured. Associations were analyzed by multivariable linear and multinomial logistic regression analyses.

Results: Among 1002 CRC survivors, 23% reported poor sleep quality (PSQI score ≥ 8) and 24% reported short sleep duration (≤ 6 h). No associations between sleep and BMI, WC, and diet quality were found.

Conclusion: Sleep problems are common in long-term CRC survivors; however, sleep quality and duration was not associated with BMI, WC, and diet quality in this population. It is unknown why the results differ from findings in the general population.
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http://dx.doi.org/10.1007/s00520-021-06393-5DOI Listing
December 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

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

Effect Modifiers and Statistical Tests for Interaction in Randomized Trials.

J Clin Epidemiol 2021 06;134:174-177

Section for Biostatistics and Evidence-Based Research, the Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark; Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, Denmark. Electronic address:

Statistical analyses of randomized controlled trials (RCTs) yield a causally valid estimate of the overall treatment effect, which is the contrast between the outcomes in two randomized treatment groups commonly accompanied by a confidence interval. In addition, the trial investigators may want to examine whether the observed treatment effect varies across patient subgroups (also called 'heterogeneity of treatment effects'), i.e. whether the treatment effect is modified by the value of a variable assessed at baseline. The statistical approach for this evaluation of potential effect modifiers is a test for statistical interaction to evaluate whether the treatment effect varies across levels of the effect modifier. In this article, we provide a concise and nontechnical explanation of the use of simple statistical tests for interaction to identify effect modifiers in RCTs. We explain how to calculate the test of interaction by hand, applied to a dataset with simulated data on 1,000 imaginary participants for illustration.
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http://dx.doi.org/10.1016/j.jclinepi.2021.03.009DOI Listing
June 2021

Levels of Inflammation Markers Are Associated with the Risk of Recurrence and All-Cause Mortality in Patients with Colorectal Cancer.

Cancer Epidemiol Biomarkers Prev 2021 06 26;30(6):1089-1099. Epub 2021 Mar 26.

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

Background: We investigated whether preoperative and postoperative levels of inflammation markers, which have mechanistically been linked to colorectal cancer progression, were associated with recurrence and all-cause mortality in patients with colorectal cancer.

Methods: Data of two prospective cohort studies were used. For the current analysis, patients with stage I to III colorectal cancer were considered. Data on inflammation [IL6, IL8, IL10, TNFα, high-sensitivity C-reactive protein (hsCRP), and a combined inflammatory -score] were available for 747 patients before surgery and for 614 patients after surgery. The associations between inflammation marker levels and colorectal cancer recurrence and all-cause mortality were examined using multivariable Cox proportional hazard regression models, considering patient characteristics and clinical and lifestyle factors.

Results: Higher preoperative and postoperative hsCRP levels were associated with a higher risk of recurrence [HR (95% CI), 1.15 (1.02-1.30) and 1.34 (1.16-1.55)] and all-cause mortality [HR (95% CI) 1.13 (1.01-1.28) and 1.15 (0.98-1.35)]. A doubling in IL8 levels (preoperative levels HR = 1.23; 95% CI, 1.00-1.53 and postoperative levels HR = 1.61; 95% CI, 1.23-2.12) and a higher combined inflammatory -score (preoperative HR = 1.39; 95% CI, 1.03-1.89 and postoperative HR = 1.56; 95% CI, 1.06-2.28) were associated with a higher risk of all-cause mortality, but not recurrence. No associations between IL6, IL10, and TNFα and recurrence or all-cause mortality were observed.

Conclusions: Preoperative and postoperative levels of specific inflammation markers were associated with recurrence and/or all-cause mortality.

Impact: The complex role of inflammation in cancer recurrence merits further elucidation by investigating local inflammation at the tumor site.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1752DOI Listing
June 2021

Longitudinal associations of sociodemographic, lifestyle, and clinical factors with alcohol consumption in colorectal cancer survivors up to 2 years post-diagnosis.

Support Care Cancer 2021 Oct 24;29(10):5935-5943. Epub 2021 Mar 24.

Center of Research on Psychological and Somatic disorders (CoRPS), Department of Medical and Clinical Psychology, Tilburg University, PO Box 90153, 5000, LE, Tilburg, The Netherlands.

Purpose: Alcohol consumption can lead to worse prognosis and mortality among colorectal cancer (CRC) patients. We investigated alcohol consumption of CRC survivors up to 2 years post-diagnosis, and how sociodemographic, lifestyle, and clinical factors were associated longitudinally with these habits.

Methods: We pooled longitudinal data of 910 CRC survivors from the ongoing PROCORE and EnCoRe studies with data collected at diagnosis (baseline) and 3, 6, 12, and 24 months post-diagnosis. Both studies assessed alcohol consumption, including beer, wine, and liquor. Generalized estimated equation models were used to examine changes over time in alcohol consumption and multivariable longitudinal associations of sociodemographic, lifestyle, and clinical factors with alcohol consumption.

Results: At baseline, participants were on average 67 years old, 332 (37%) were female, and alcohol was consumed by 79%. Most survivors (68-71%) drank less at all follow-ups. Beer, wine, and liquor were consumed by 51%, 58%, and 25% at baseline, respectively, and these declined over time. Males consumed more alcohol, and higher education, more physical activity, and not having a (permanent) stoma were associated with consuming more alcohol.

Conclusion: CRC survivors decreased their alcohol consumption in the 2 years post-diagnosis. Future studies should take the significant factors that were associated with alcohol post-diagnosis consumption into account, when they investigate CRC health outcomes or for identifying subgroups for interventions. Males with higher education, more physical activity, and no stoma should be reminded after diagnosis for reducing their alcohol consumption.
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http://dx.doi.org/10.1007/s00520-021-06104-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410706PMC
October 2021

Lifestyle after colorectal cancer diagnosis in relation to recurrence and all-cause mortality.

Am J Clin Nutr 2021 06;113(6):1447-1457

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

Background: An unhealthy lifestyle is associated with the risk of colorectal cancer (CRC), but it is unclear whether overall lifestyle after a CRC diagnosis is associated with risks of recurrence and mortality.

Objectives: To examine associations between postdiagnosis lifestyle and changes in lifestyle after a CRC diagnosis with risks of CRC recurrence and all-cause mortality.

Methods: The study population included 1425 newly diagnosed, stage I-III CRC patients from 2 prospective cohort studies enrolled between 2010 and 2016. Lifestyle, including BMI, physical activity, diet, and alcohol intake, was assessed at diagnosis and at 6 months postdiagnosis. We assigned lifestyle scores based on concordance with 2 sets of cancer prevention guidelines-from the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) and the American Cancer Society (ACS)-and national disease prevention guidelines. Higher scores indicate healthier lifestyles. We computed adjusted HRs and 95% CIs using Cox regression.

Results: We observed 164 recurrences during a 2.8-year median follow-up and 171 deaths during a 4.4-year median follow-up. No associations were observed for CRC recurrence. A lifestyle more consistent with the ACS recommendations was associated with a lower all-cause mortality risk (HR per +1 SD, 0.85; 95% CI: 0.73-0.995). The same tendency was observed for higher WCRF/AICR (HR, 0.92; 95% CI: 0.78-1.08) and national (HR, 0.90; 95% CI: 0.77-1.05) lifestyle scores, although these associations were statistically nonsignificant. Generally, no statistically significant associations were observed for BMI, physical activity, diet, or alcohol. Improving one's lifestyle after diagnosis (+1 SD) was associated with a lower all-cause mortality risk for the ACS (HR, 0.80; 95% CI: 0.67-0.96) and national (HR, 0.84; 95% CI: 0.70-0.999) scores, yet was statistically nonsignificant for the WCRF/AICR score (HR, 0.94; 95% CI: 0.78-1.13).

Conclusions: A healthy lifestyle after CRC diagnosis and improvements therein were not associated with the risk of CRC recurrence, but were associated with a decreased all-cause mortality risk.
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http://dx.doi.org/10.1093/ajcn/nqaa394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168353PMC
June 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

Tutorial: A nontechnical explanation of the counterfactual definition of effect modification and interaction.

J Clin Epidemiol 2021 06 4;134:113-124. Epub 2021 Feb 4.

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

Effect modification and interaction are important concepts for answering causal questions about interdependent effects of two (or more) exposures on some outcome of interest. Although conceptually alike and often mistakenly regarded as synonymous, effect modification and interaction actually refer to slightly different concepts when considered from a causal perspective. Their subtle yet relevant distinction lies in how the interplay between exposures is defined and the causal roles attributed to the exposures involved in the effect modification and interaction. To gain more insight into similarities and differences between the concepts of effect modification and interaction, the counterfactual theory of causation, albeit complicated, can be very helpful. Therefore, this article presents a nontechnical explanation of the counterfactual definition of effect modification and interaction. Essentially, effect modification and interaction are reflections of the reality and complexity of multicausality. The causal effect of an exposure of interest often depends on the levels of other exposures (effect modification) or causal effects of other exposures (interaction). Consequently, exposure effects should not be regarded in isolation but in combination. Understanding the underlying principles of effect modification and interaction on a conceptual level enables researchers to better anticipate, detect, and interpret these causal phenomena when setting up, analyzing, and reporting findings of (clinical) epidemiological studies. Effect modification and interaction are not biases to be avoided but properties of causal effects that ought to be unveiled. Hence, evidence for effect modification and interaction needs to be shown in order to delineate in whom and which instances causal effects occur.
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http://dx.doi.org/10.1016/j.jclinepi.2021.01.022DOI Listing
June 2021

Sufficient 25-Hydroxyvitamin D Levels 2 Years after Colorectal Cancer Diagnosis are Associated with a Lower Risk of All-cause Mortality.

Cancer Epidemiol Biomarkers Prev 2021 04 2;30(4):765-773. Epub 2021 Feb 2.

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

Background: Whether changes in 25 hydroxy vitamin D (25(OH)D) levels after colorectal cancer diagnosis influence clinical outcomes is unclear. We investigated the association of trajectories of 25(OH)D levels with recurrence and all-cause mortality.

Methods: In total, 679 patients were included in our data analyses. Trajectories of 25(OH)D levels were defined on the basis of vitamin D status at diagnosis, at 6 months, and 2 years after diagnosis. Observed trajectories of 25(OH)D levels were consistent deficient levels (20%), consistent sufficient levels (39%), increasing levels (20%), and a temporary drop in levels (13%). Associations of trajectories of 25(OH)D with recurrence and all-cause mortality were assessed using multivariable Cox proportional hazards regression models.

Results: During a follow-up time of 2.2 years for recurrence and 3.5 years for all-cause mortality, 31 and 65 events occurred, respectively. No statistically significant associations were observed for vitamin D trajectories and the risk of recurrence. Patients who were consistently sufficient compared with patients who were consistently deficient had a lower risk of all-cause mortality [HR 0.39; 95% confidence interval (CI), 0.21-0.73]. The risk of all-cause mortality seems lower in patients with increasing levels or a temporary drop in levels (HR 0.54; 95% CI, 0.27-1.10 and HR 0.40 95% CI, 0.17-0.93) relative to patients with consistent deficient levels.

Conclusions: Patients with colorectal cancer following a trajectory characterized by sufficient levels of 25(OH)D 2 years after diagnosis all appeared to have a lower risk of all-cause mortality compared with patients having consistent deficient levels.

Impact: Further studies should investigate how trajectories of 25(OH)D levels are associated with colorectal cancer recurrence.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1388DOI Listing
April 2021

Inflammation Is a Mediating Factor in the Association between Lifestyle and Fatigue in Colorectal Cancer Patients.

Cancers (Basel) 2020 12 9;12(12). Epub 2020 Dec 9.

Division of Human Nutrition and Health, Wageningen University, 6708 WE Wageningen, The Netherlands.

Fatigue is very common among colorectal cancer (CRC) patients. We examined the association between adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) lifestyle recommendations and fatigue among stage I-III CRC patients, and whether inflammation mediated this association. Data from two prospective cohort studies were used. Adherence to the WCRF/AICR recommendations was expressed as a score ranging from 0-7, and assessed shortly after diagnosis. Six months post-diagnosis, fatigue was assessed with the European Organization for Research and Treatment of Cancer quality of life questionnaire C30 (EORTC QLQ-C30), and in a subpopulation, the plasma levels of inflammation markers (IL6, IL8, TNFα, and hsCRP) were assessed. Multiple linear regression analyses were performed to investigate the association between adherence to the WCRF/AICR recommendations and fatigue. To test mediation by inflammation, the PROCESS analytic tool developed by Hayes was used. A higher WCRF/AICR adherence score was associated with less fatigue six months after diagnosis ( = 1417, β -2.22, 95%CI -3.65; -0.78). In the population of analysis for the mediation analyses ( = 551), the total association between lifestyle and fatigue was (β -2.17, 95% CI -4.60; 0.25). A statistically significant indirect association via inflammation was observed (β -0.97, 95% CI -1.92; -0.21), explaining 45% of the total association between lifestyle and fatigue (-0.97/-2.17 × 100). Thus, inflammation is probably one of the underlying mechanisms linking lifestyle to fatigue.
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http://dx.doi.org/10.3390/cancers12123701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763620PMC
December 2020

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

The association between circulating levels of vitamin D and inflammatory markers in the first 2 years after colorectal cancer diagnosis.

Therap Adv Gastroenterol 2020 27;13:1756284820923922. Epub 2020 May 27.

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

Background: Calcitriol, the active form of vitamin D, may inhibit colorectal cancer (CRC) progression, which has been mechanistically linked to an attenuation of a pro-inflammatory state. The present study investigated the associations between circulating 25 hydroxy vitamin D (25(OH)D) levels and inflammatory markers (IL10, IL8, IL6, TNFα and hsCRP) in the 2 years following CRC diagnosis.

Methods: Circulating 25(OH)D levels and inflammatory markers were assessed at diagnosis, after 6, 12 and 24 months from 798 patients with sporadic CRC participating in two prospective cohort studies. Associations between 25(OH)D levels and individual inflammatory markers as well as a summary inflammatory -score were assessed at each time point by multiple linear regression analyses. To assess the association between 25(OH)D and inflammatory markers over the course of 2 years, linear mixed model regression analyses were conducted.

Results: Higher 25(OH)D levels were associated with lower IL6 levels at diagnosis, at 6 months after diagnosis and over the course of 2 years (β -0.06, 95% CI -0.08 to -0.04). In addition, 25(OH)D levels were inversely associated with the summary inflammatory -score at diagnosis and over the course of 2 years (β -0.17, 95% CI -0.25 to -0.08). In addition, a significant inverse association between 25(OH)D levels and IL10 was found over the course of 2 years. Intra-individual analyses showed an inverse association between 25(OH)D and IL10, IL6 and TNFα. No statistically significant associations between 25(OH)D and IL8 and hsCRP levels were observed.

Conclusions: Serum 25(OH)D levels were inversely associated with the summary inflammatory -score and in particular with IL6 in the years following CRC diagnosis. This is of potential clinical relevance as IL6 has an important role in chronic inflammation and is also suggested to stimulate cancer progression. Further observational studies should investigate whether a possible 25(OH)D-associated reduction of inflammatory mediators influences treatment efficacy and CRC recurrence.
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http://dx.doi.org/10.1177/1756284820923922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273344PMC
May 2020

The reproducibility of skeletal muscle signal intensity on routine magnetic resonance imaging in Crohn's disease.

J Gastroenterol Hepatol 2020 Nov 27;35(11):1902-1908. Epub 2020 Apr 27.

Division of Gastroenterology-Hepatology, Maastricht University Medical Centre+, Maastricht, The Netherlands.

Background And Aim: Myosteatosis is a prognostic factor in cancer and liver cirrhosis. It can be determined noninvasively using computed tomography or, as shown recently, by magnetic resonance (MR) imaging. The primary aim was to analyze the reproducibility of skeletal muscle signal intensity on routine MR-enterographies, as indicator of myosteatosis, in Crohn's disease (CD) and to explore the association between skeletal muscle signal intensity at diagnosis with time to intestinal resection.

Methods: CD patients undergoing MR-enterography within 6 months from diagnosis and having a maximum of 5 years follow-up were included. Skeletal muscle signal intensity was analyzed on T1-weighted fat-saturated post-contrast images. Intra-observer and inter-observer reproducibilities were assessed by intra-class correlation coefficient and Cohen's kappa. Intra-observer and inter-observer variabilities were determined by Pearson correlation coefficient and displayed by Bland-Altman plots. Time to intestinal resection was studied by Kaplan-Meier analysis.

Results: Median time between diagnosis and MR-enterography was 5 weeks (inter-quartile range 1-9) in 35 CD patients. Skeletal muscle signal intensity showed good intra-class correlation and substantial agreement (for intra-observer, intraclass correlation coefficient = 0.948, κ = 0.677; and inter-observer reproducibility, intraclass correlation coefficient = 0.858, κ = 0.622). Resection free survival was shorter in the low skeletal muscle signal intensity group (P = 0.037).

Conclusion: Skeletal muscle signal intensity on routine MR-enterographies is reproducible and was associated with unfavorable disease outcome, indicating potential clinical relevance.
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http://dx.doi.org/10.1111/jgh.15068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687168PMC
November 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

Vitamin D, magnesium, calcium, and their interaction in relation to colorectal cancer recurrence and all-cause mortality.

Am J Clin Nutr 2020 05;111(5):1007-1017

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

Background: Higher concentrations of 25-hydroxyvitamin D3 [25(OH)D3] at diagnosis are associated with a lower mortality risk in colorectal cancer (CRC) patients. However, magnesium and calcium are important in vitamin D metabolism.

Objectives: We aimed to investigate 25(OH)D3, magnesium, or calcium and their interaction among patients with CRC in relation to recurrence and all-cause mortality.

Methods: The study population included 1169 newly diagnosed stage I-III CRC patients from 2 prospective cohorts. Associations between 25(OH)D3 concentrations, magnesium or calcium intake through diet and/or supplements at diagnosis, and recurrence and all-cause mortality were evaluated using multivariable Cox proportional hazard models. The interaction between 25(OH)D3 and magnesium or calcium was assessed by investigating 1) joint compared with separate effects, using a single reference category; and 2) the effect estimates of 1 factor across strata of another.

Results: Serum 25(OH)D3, calcium, and magnesium, alone and their interactions, were not associated with recurrence. Serum 25(OH)D3 concentrations seemed to be associated with all-cause mortality. An inverse association between magnesium intake (HRQ3 vs. Q1: 0.55; 95% CI: 0.32, 0.95 and HRQ4 vs. Q1: 0.65; 95% CI: 0.35, 1.21), but not calcium intake, and all-cause mortality was observed. When investigating the interaction between 25(OH)D3 and magnesium, we observed the lowest risk of all-cause mortality in patients with sufficient vitamin D concentrations (≥50 nmol/L) and a high magnesium intake (median split) (HR: 0.53; 95% CI: 0.31, 0.89) compared with patients who were vitamin D deficient (<50 nmol/L) and had a low magnesium intake. No interactions between calcium and vitamin D in relation to all-cause mortality were observed.

Conclusions: Our findings suggest that the presence of an adequate status of 25(OH)D3 in combination with an adequate magnesium intake is essential in lowering the risk of mortality in CRC patients, yet the underlying mechanism should be studied. In addition, diet and lifestyle intervention studies are needed to confirm our findings. The COLON study was registered at clinicaltrials.gov as NCT03191110. The EnCoRe study was registered at trialregister.nl as NTR7099.
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http://dx.doi.org/10.1093/ajcn/nqaa049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198285PMC
May 2020

Development and internal validation of prediction models for colorectal cancer survivors to estimate the 1-year risk of low health-related quality of life in multiple domains.

BMC Med Inform Decis Mak 2020 03 12;20(1):54. Epub 2020 Mar 12.

Department of Epidemiology, GROW - School for Oncology and Developmental Biology, Maastricht University, P. Debyeplein 1, 6200, MD, Maastricht, the Netherlands.

Background: Many colorectal cancer (CRC) survivors experience persisting health problems post-treatment that compromise their health-related quality of life (HRQoL). Prediction models are useful tools for identifying survivors at risk of low HRQoL in the future and for taking preventive action. Therefore, we developed prediction models for CRC survivors to estimate the 1-year risk of low HRQoL in multiple domains.

Methods: In 1458 CRC survivors, seven HRQoL domains (EORTC QLQ-C30: global QoL; cognitive, emotional, physical, role, social functioning; fatigue) were measured prospectively at study baseline and 1 year later. For each HRQoL domain, scores at 1-year follow-up were dichotomized into low versus normal/high. Separate multivariable logistic prediction models including biopsychosocial predictors measured at baseline were developed for the seven HRQoL domains, and internally validated using bootstrapping.

Results: Average time since diagnosis was 5 years at study baseline. Prediction models included both non-modifiable predictors (age, sex, socio-economic status, time since diagnosis, tumor stage, chemotherapy, radiotherapy, stoma, micturition, chemotherapy-related, stoma-related and gastrointestinal complaints, comorbidities, social inhibition/negative affectivity, and working status) and modifiable predictors (body mass index, physical activity, smoking, meat consumption, anxiety/depression, pain, and baseline fatigue and HRQoL scores). Internally validated models showed good calibration and discrimination (AUCs: 0.83-0.93).

Conclusions: The prediction models performed well for estimating 1-year risk of low HRQoL in seven domains. External validation is needed before models can be applied in practice.
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http://dx.doi.org/10.1186/s12911-020-1064-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068880PMC
March 2020

Associations of Abdominal Skeletal Muscle Mass, Fat Mass, and Mortality among Men and Women with Stage I-III Colorectal Cancer.

Cancer Epidemiol Biomarkers Prev 2020 05 4;29(5):956-965. Epub 2020 Mar 4.

Department of Research & Development, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, the Netherlands.

Background: The associations of abdominal skeletal muscle mass index (SMI), visceral and subcutaneous adipose tissue (VAT and SAT, respectively), and mortality among patients with stage I-III colorectal cancer may differ for men and women, but only few studies stratified their data into men and women. We investigated associations of abdominal SMI, VAT, and SAT with overall mortality among men and among women with stage I-III colorectal cancer.

Methods: SMI, VAT, and SAT were assessed from abdominal CT images for 1,998 patients with stage I-III colorectal cancer diagnosed between 2006 and 2015. Restricted cubic splines (RCS) were used to investigate associations of SMI, VAT, and SAT with overall mortality.

Results: Average age of the participants was 67.9 ± 10.6 years and 58% were men. During a median follow-up of 4.3 years, 546 (27%) patients died. Among men, the association of SMI and mortality was statistically significant in a nonlinear way in the RCS analyses, with lower SMI levels associated with higher mortality. SMI was not associated with mortality among women. SAT was associated with mortality in a nonlinear way for men and for women, with lower SAT levels being associated with higher mortality. VAT was not significantly associated with mortality in men or women.

Conclusion: Associations of abdominal skeletal muscle mass with mortality among patients with colorectal cancer were not the same for men and for women.

Impact: This study stresses the importance for more attention on sex-related differences in body composition and cancer outcomes.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-1134DOI Listing
May 2020

A nontechnical explanation of the counterfactual definition of confounding.

J Clin Epidemiol 2020 05 14;121:91-100. Epub 2020 Feb 14.

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

In research addressing causal questions about relations between exposures and outcomes, confounding is an issue when effects of interrelated exposures on an outcome are confused. For making valid inferences about cause-and-effect relationships, the biasing influence of confounding must be controlled by design or eliminated during data analysis. Consequently, researchers require a sound understanding of the concept of confounding to adequately deal with this type of bias when setting up and conducting (clinical) epidemiological research. For explaining confounding on a conceptual level, the counterfactual framework for causal inference is invaluable but can be very complicated. In this article, therefore, a nontechnical explanation of the counterfactual definition of confounding is presented. When considering confounding in a counterfactual way, the principle of exchangeability plays a pivotal role. Causal effects of an exposure on an outcome can be evaluated only when different exposure groups have comparable background risks of the outcome. Then, exposure groups are exchangeable and thus unconfounded. By providing a simplified explanation of the counterfactual principles of exchangeability, and consequences of nonexchangeability, this article aims to increase understanding of confounding on a conceptual level as well as the rationale underlying design and analytic strategies for dealing with confounding in (clinical) epidemiological research.
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http://dx.doi.org/10.1016/j.jclinepi.2020.01.021DOI Listing
May 2020

The impact of participation restrictions on everyday life in long-term colorectal cancer survivors in the EnCoRe study: A mixed-method study.

Eur J Oncol Nurs 2020 Apr 1;45:101724. Epub 2020 Feb 1.

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

Purpose: Knowledge about long-term colorectal cancer (CRC) or treatment related health and functioning problems and on its impact on participation of CRC survivors in domestic life and in society is limited. We aimed to explore the nature and impact of cancer (treatment) related participation restrictions on everyday life of long-term CRC survivors, their current satisfaction with participation, and associations of health and functioning problems with participation satisfaction, using the International Classification of Functioning, Disability and Health (ICF) to comprehensively study participation.

Method: Mixed-method study in 2-10 years post-diagnosis stage I-III CRC survivors (n = 151) from the cross-sectional part of the EnCoRe study. Participation restrictions were explored by semi-structured interviews in a subsample reporting participation restrictions (n = 10). Role functioning (SF36-Health Survey), fatigue (Checklist Individual Strength), and peripheral neuropathy symptoms (EORTC QLQ-CIPN20) were assessed in all participants and associations with self-reported participation satisfaction were analyzed by multivariable logistic regression models.

Results: 19% of CRC survivors reported dissatisfaction with participation. Participation restrictions were reported for interpersonal relationships, work/employment, and social/civic life. CRC survivors reporting better physical and emotional role functioning were significantly less likely to be dissatisfied with their participation, whereas survivors reporting higher levels of fatigue or more peripheral neuropathy symptoms were more likely to be dissatisfied with participation.

Conclusions: Colorectal cancer (treatment) related health and functioning problems negatively impacts the ability of nearly 1 in 5 long-term CRC survivors to participate in everyday life situations and their satisfaction with participation. Follow-up care needs to be able to identify and address these problems.
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http://dx.doi.org/10.1016/j.ejon.2020.101724DOI Listing
April 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
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