We previously demonstrated that intake of low‐fat dairy, but not high‐fat dairy, was associated with a decreased colorectal cancer (CRC) recurrence risk. These risks, however, may differ by sex, ...primary tumour location, and disease stage. Combining data from two similar prospective cohort studies of people with stage I–III CRC enabled these subgroup analyses. Participants completed a food frequency questionnaire at diagnosis (n = 2283). We examined associations between low‐ and high‐fat dairy intake and recurrence risk using multivariable Cox proportional hazard models, stratified by sex, and primary tumour location (colon and rectum), and disease stage (I/II and III). Upper quartiles were compared to lower quartiles of intake, and recurrence was defined as a locoregional recurrence and/or metastasis. During a median follow‐up of 5.0 years, 331 recurrences were detected. A higher intake of low‐fat dairy was associated with a reduced risk of recurrence (hazard ratio HR: 0.60, 95% confidence interval CI: 0.43–0.83), which seemed more pronounced in men (HR: 0.51, 95% CI: 0.34–0.77) than in women (HR: 0.84, 95% CI: 0.47–1.49). A higher intake of high‐fat dairy was associated with an increased risk of recurrence in participants with colon cancer (HR: 1.60, 95% CI: 1.03–2.50), but not rectal cancer (HR: 0.88, 95% CI: 0.54–1.45). No differences in associations were observed between strata of disease stage. Concluding, our findings imply that dietary advice regarding low‐fat dairy intake may be especially important for men with CRC, and that dietary advice regarding high‐fat dairy intake may be specifically important in people with colon cancer.
What's new?
There is strong evidence that dairy intake is associated with a reduced risk of developing colorectal cancer. However, its relation to the risk of colorectal cancer recurrence remains unclear. Combining data from two prospective cohort studies of patients with stage I–III colorectal cancer, this study found that a higher intake of low‐fat dairy was associated with a reduced risk of recurrence in men, where as a higher intake of high‐fat dairy was associated with an increased risk of recurrence in people with colon cancer. With a global transition towards more plant‐based diets and increasing numbers of colorectal cancer survivors, the findings may contribute to more personalised dietary guidelines.
Coffee consumption has been associated with a reduced risk of developing colorectal cancer (CRC). However, it is not clear whether coffee consumption is related to CRC progression. Hence, we assessed ...the association of coffee consumption with CRC recurrence and all‐cause mortality using data from a prospective cohort study of 1719 stage I–III CRC patients in the Netherlands. Coffee consumption and other lifestyle characteristics were self‐reported using questionnaires at the time of diagnosis. We retrieved recurrence and all‐cause mortality data from the Netherlands Cancer Registry and the Personal Records Database, respectively. Cox proportional hazard regression models with and without restricted cubic splines were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) adjusted for age, sex, education, smoking status, cancer stage and tumor location. We observed 257 recurrences during a 6.2‐year median follow‐up and 309 deaths during a 6.6‐year median follow‐up. Consuming more than 4 cups/d of coffee compared to an intake of <2 cups/d was associated with a 32% lower risk of CRC recurrence (95% CI: 0.49, 0.94,). The association between coffee consumption and all‐cause mortality was U‐shaped; coffee intake seemed optimal at 3–5 cups/d with the lowest risk at 4 cups/d (HR: 0.68, 95% CI: 0.53, 0.88). Our results suggest that coffee consumption may be associated with a lower risk of CRC recurrence and all‐cause mortality. The association between coffee consumption and all‐cause mortality appeared nonlinear. More studies are needed to understand the mechanism by which coffee consumption might improve CRC prognosis.
What's new?
Although existing evidence suggests that coffee consumption may lower colorectal cancer risk, the association with colorectal cancer prognosis remains unclear. This large prospective study of stage I–III patients in a country with a relatively high coffee intake revealed a strong inverse association between coffee consumption and colorectal cancer recurrence. The association between coffee consumption and all‐cause mortality in colorectal cancer patients was nonlinear, suggesting an optimal intake of three to five cups per day. The findings could potentially inform future intervention studies as well as dietary guidelines for colorectal cancer patients.
Colorectal cancer is known to arise from multiple tumorigenic pathways; however, the underlying mechanisms remain not completely understood. Metabolomics is becoming an increasingly popular tool in ...assessing biological processes. Previous metabolomics research focusing on colorectal cancer is limited by sample size and did not replicate findings in independent study populations to verify robustness of reported findings. Here, we performed a ultrahigh performance liquid chromatography‐quadrupole time‐of‐flight mass spectrometry (UHPLC‐QTOF‐MS) screening on EDTA plasma from 268 colorectal cancer patients and 353 controls using independent discovery and replication sets from two European cohorts (ColoCare Study: n = 180 patients/n = 153 controls; the Colorectal Cancer Study of Austria (CORSA) n = 88 patients/n = 200 controls), aiming to identify circulating plasma metabolites associated with colorectal cancer and to improve knowledge regarding colorectal cancer etiology. Multiple logistic regression models were used to test the association between disease state and metabolic features. Statistically significant associated features in the discovery set were taken forward and tested in the replication set to assure robustness of our findings. All models were adjusted for sex, age, BMI and smoking status and corrected for multiple testing using False Discovery Rate. Demographic and clinical data were ed from questionnaires and medical records.
What's new?
Colorectal cancer exhibits certain characteristic changes in metabolic pathways. To expand upon previous findings, these authors performed a discovery‐replication study using two large independent study populations from different countries, Germany and Austria. They tested metabolic profiles of cancer patients and controls, identifying 691 statistically significant features in the discovery cohort. Testing the second cohort narrowed it to 97. These corresponded to 28 metabolites, of which 15 could be identified. It will be useful to go forward with prospective analysis on these 15 metabolites, to determine whether they have predictive or prognostic value.
Abstract
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.
The authors investigated the association of adherence to Mediterranean diet with colorectal cancer (CRC) risk in the European Prospective Investigation into Cancer and nutrition study. Adherence to ...Mediterranean diet was expressed through two 10-unit scales, the Modified Mediterranean diet score (MMDS) and the Centre-Specific MMDS (CSMMDS). Both scales share the same dietary components but differ in the cut-off values that were used for these components in the construction of the scales. Adjusted hazard ratios (HR) for the associations of these scales with CRC incidence were estimated. After 5,296,617 person-years of follow-up, 4,355 incident CRC cases were identified. A decreased risk of CRC, of 8 and 11 % was estimated when comparing the highest (scores 6–9) with the lowest (scores 0–3) adherence to CSMMDS and MMDS respectively. For MMDS the HR was 0.89 (95 % confidence interval (CI): 0.80, 0.99). A 2-unit increment in either Mediterranean scale was associated with a borderline statistically significant 3 to 4 % reduction in CRC risk (HR for MMDS: 0.96; 95 % CI: 0.92, 1.00). These associations were somewhat more evident, among women, were mainly manifested for colon cancer risk and their magnitude was not altered when alcohol was excluded from MMDS. These findings suggest that following a Mediterranean diet may have a modest beneficial effect on CRC risk.
Aim
Colorectal anastomotic leakage (AL) is a serious complication. Studies on the impact of AL on health‐related quality of life (HRQoL) are scarce. We aimed to investigate the association between AL ...and HRQoL in colorectal cancer patients up to 2 years after diagnosis, and to evaluate whether AL is associated with a clinically relevant decrease in HRQoL over time.
Methods
Patients diagnosed with Stage I–III colorectal cancer undergoing elective surgical resection with primary anastomosis between 2010 and 2017 were included. HRQoL was evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30, represented by the summary score, and analysed at diagnosis and at 6 months and 2 years post‐diagnosis. Multivariable linear regression was performed to assess the association between AL and HRQoL, while multivariable logistic regression was used to investigate the association between AL and a clinically relevant HRQoL decrease (≥10 points) during follow‐up compared to the time of diagnosis.
Results
In total, 1197 patients were included of whom 63 (5%) developed AL. AL was not associated with HRQoL at 6 months post‐diagnosis nor at 2 years post‐diagnosis. However, having AL was associated with an increased risk of a clinically relevant decrease in HRQoL at 6 months post‐diagnosis (OR 3.65, 95% CI 1.62–8.21) but not at 2 years after diagnosis (OR 1.91, 95% CI 0.62–5.93).
Conclusion
Although AL was not associated with HRQoL at 6 months or 2 years post‐diagnosis, AL was a determinant of a clinically relevant decrease in HRQoL at 6 months after diagnosis. Future work should identify feasible and effective strategies to prevent declines in QoL in this patient population.
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.
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.
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.
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.
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.
Colorectal cancer (CRC) is increasingly recognized as a heterogeneous disease. No studies have prospectively examined associations of blood metabolite concentrations with all-cause mortality in ...patients with colon and rectal cancer separately. Targeted metabolomics (Biocrates Absolute
p180) and pathway analyses (MetaboAnalyst 4.0) were performed on pre-surgery collected plasma from 674 patients with non-metastasized (stage I-III) colon (
= 394) or rectal cancer (
= 283). Metabolomics data and covariate information were received from the international cohort consortium MetaboCCC. Cox proportional hazards models were computed to investigate associations of 148 metabolite levels with all-cause mortality adjusted for age, sex, tumor stage, tumor site (whenever applicable), and cohort; the false discovery rate (FDR) was used to account for multiple testing. A total of 93 patients (14%) were deceased after an average follow-up time of 4.4 years (60 patients with colon cancer and 33 patients with rectal cancer). After FDR adjustment, higher plasma creatinine was associated with a 39% increase in all-cause mortality in patients with rectal cancer. HR: 1.39, 95% CI 1.23-1.72, p
= 0.03; but not colon cancer: p
= 0.96. Creatinine is a breakdown product of creatine phosphate in muscle and may reflect changes in skeletal muscle mass. The starch and sucrose metabolisms were associated with increased all-cause mortality in colon cancer but not in rectal cancer. Genes in the starch and sucrose metabolism pathways were previously linked to worse clinical outcomes in CRC. In summary, our findings support the hypothesis that colon and rectal cancer have different etiological and clinical outcomes that need to be considered for targeted treatments.
Purpose
A healthy diet reduces the risk of non-alcoholic fatty liver disease (NAFLD) in the general population, especially in individuals who are genetically predisposed to NAFLD. Little is known in ...patients who suffered from a myocardial infarction (MI). We examined the interaction between diet quality and genetic predisposition in relation to NAFLD in post-MI patients.
Methods
We included 3437 post-MI patients from the Alpha Omega Cohort. Diet quality was assessed with adherence to the Dutch Healthy Diet index 2015 (DHD15-index). A weighted genetic risk score (GRS) for NAFLD was computed using 39 genetic variants. NAFLD prevalence was predicted using the Fatty Liver Index. Prevalence ratios (PR) with 95% confidence intervals of DHD15-index and GRS in relation to NAFLD were obtained with multivariable Cox proportional hazards models. The interaction between DHD15-index and GRS in relation to NAFLD was assessed on an additive and multiplicative scale.
Results
Patients had a mean age of 69 (± 5.5) years, 77% was male and 20% had diabetes. The DHD15-index ranged from 28 to 120 with a mean of 73. Patients with higher diet quality were less likely to suffer from NAFLD, with a PR of 0.76 (0.62, 0.92) for the upper vs lower quintile of DHD15-index. No association between the GRS and NAFLD prevalence was found (PR of 0.92 0.76, 1.11). No statistically significant interaction between the DHD15-index and GRS was observed.
Conclusion
In Dutch post-MI patients, adherence to the Dutch dietary guidelines was associated with a lower prevalence of NAFLD, as assessed by the FLI. This association was present regardless of genetic predisposition in this older aged cohort.
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 gastrointestinal problems.
Because of the therapeutic potential of dietary fiber on the gut, we aim to assess longitudinal associations of postdiagnostic dietary fiber, fruit, and vegetable intake, a major source of dietary fiber, with HRQoL, fatigue, CIPN, and gastrointestinal symptoms in CRC survivors from 6 wk to 24 mo posttreatment.
In a prospective cohort among stage I–III CRC survivors (n = 459), 5 repeated study measurements between diagnosis and 24 mo posttreatment were executed. Dietary fiber intake and fruit and vegetable intake were measured by 7-d dietary records. HRQoL, fatigue, CIPN, and gastrointestinal symptoms were measured by validated questionnaires. We applied confounder-adjusted linear mixed models to analyze longitudinal associations from 6 wk until 24 mo posttreatment and used hybrid models to disentangle the overall association into intraindividual changes and interindividual differences over time.
Higher dietary fiber intake and fruit and vegetable intake were longitudinally associated with statistically significant better physical functioning and less fatigue. Intraindividual 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 gastrointestinal symptoms.
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 2 y after the end of treatment for CRC.
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