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Early-onset colorectal cancer has been on the rise in Western populations. Here, we compare patient characteristics between those with early- (

Purpose: To characterize dietary patterns and examine associations with cross-sectional and longitudinal changes in quality of life (QOL) over approximately one year after colorectal cancer (CRC) diagnosis. Methods: The ColoCare Study is an international, multi-center, prospective cohort study of newly diagnosed CRC survivors of any stage. A subset of participants with CRC in the United States completed patient-reported outcome measures at 6- and 12-months post-enrollment, including the Food Frequency Questionnaire (FFQ) and European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Dietary patterns at 6 months (around the time of treatment completion) were identified using Principal Component Analysis (PCA) with varimax rotation. Adherence scores were calculated for participants within each dietary pattern, with higher scores indicating higher adherence. Mixed models were used to examine the effect of each dietary pattern on changes in QOL at 6- and 12-month follow-ups, controlling for cancer stage, biological sex, body mass index (BMI), smoking status, and age. Results: Participants (N = 174) were, on average, 56 ± 14 years old and were mostly female (51.5%), stage III or IV (51.7%), never smokers (60.2%), non-Hispanic (97.1%), and White (83.3%) with a BMI of 27.9 ± 6.1 kg/m2. PCA revealed two emerging dietary patterns: "Western diet", characterized by processed meats, refined grains, and sugars, and "Prudent diet" characterized by lean proteins, fruits, and vegetables. Higher adherence to a Western diet was associated with worse social functioning at 6-month follow-up (FE = −12.6, p = 0.010). Loss of appetite from 6 to 12 months was associated with higher adherence to both the Western and Prudent dietary patterns (FE = 1.5, p = 0.044; FE = 1.3, p = 0.046, respectively). Neither dietary pattern was associated with global QOL score at 6- or 12-month follow-up (p's > 0.05). Conclusions: Among CRC survivors in the United States, the Western diet was concurrently associated with worse social functioning. Loss of appetite was reported by CRC survivors following both dietary patterns, suggesting that loss of appetite may be a global experience for CRC survivors during this timeframe. Further research is needed to understand specific social challenges experienced by CRC survivors and develop supportive care interventions to address appetite and nutritional concerns. [ABSTRACT FROM AUTHOR]

Background: Cachexia accounts for about 20% of all cancer‐related deaths and indicates poor prognosis. The impact of Fusobacterium nucleatum (Fn), a microbial risk factor for colorectal cancer (CRC), on the development of cachexia in CRC has not been established. Methods: We evaluated the association between Fn abundance in pre‐surgical stool samples and onset of cachexia at 6 months post‐surgery in n = 87 patients with stages I–III CRC in the ColoCare Study. Results: High fecal Fn abundance compared to negative/low fecal Fn abundance was associated with 4‐fold increased risk of cachexia onset at 6 months post‐surgery (OR = 4.82, 95% CI = 1.15, 20.10, p = 0.03). Conclusion: Our findings suggest that high fecal Fn abundance was associated with an increased risk of cachexia at 6 months post‐surgery in CRC patients. This is the first study to link Fn abundance with cachexia in CRC patients, offering novel insights into biological mechanisms and potential management of cancer cachexia. Due to the small sample size, our results should be interpreted with caution. Future studies with larger sample sizes are needed to validate these findings. [ABSTRACT FROM AUTHOR]

Fatigue is prevalent in colorectal cancer (CRC) survivors, impacting their health‐related quality of life (HRQoL). Inflammation‐induced activation of the kynurenine pathway may play a role in cancer‐related fatigue and HRQoL, but evidence is scarce. Therefore, we aimed to investigate longitudinal associations of plasma tryptophan, kynurenines, and ratios with fatigue and HRQoL in CRC survivors up to 12 months post‐treatment. Repeated measurements at 6 weeks, 6 months, and 12 months post‐treatment were performed in 249 stage I‐III CRC survivors. Plasma tryptophan and eight kynurenines were analyzed using liquid chromatography‐tandem mass spectrometry (LC/MS–MS). Fatigue and HRQoL outcomes were evaluated using validated questionnaires. Confounder‐adjusted linear mixed models were conducted to analyze longitudinal associations, with false discovery rate (FDR) correction. Higher tryptophan (Trp), kynurenic acid (KA), and xanthurenic acid (XA) concentrations, as well as a higher kynurenic acid‐to‐quinolinic acid ratio (KA/QA), were associated with less fatigue and better functioning, while a higher kynurenine‐to‐tryptophan ratio (KTR) and 3‐hydroxykynurenine ratio (HKr) were associated with more fatigue and worse functioning. Finally, higher KA and XA concentrations and a higher KA/QA ratio were associated with a higher overall HRQoL summary score, while a higher HKr was associated with a lower overall HRQoL summary score. In conclusion, we observed that tryptophan and several kynurenines were longitudinally associated with fatigue and HRQoL in CRC survivors up to 12 months post‐treatment. Future research is needed to validate our findings and explore the potential of the kynurenine pathway as intervention target for reducing fatigue and enhancing HRQoL after CRC treatment. [ABSTRACT FROM AUTHOR]

BackgroundMetabolic and transcriptomic differences between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) compartments, particularly in the context of obesity, may play a role in colorectal carcinogenesis. We investigated the differential functions of their metabolic compositions.ObjectivesBiochemical differences between adipose tissues (VAT compared with SAT) in patients with colorectal carcinoma (CRC) were investigated by using mass spectrometry metabolomics and gene expression profiling. Metabolite compositions were compared between VAT, SAT, and serum metabolites. The relation between patients' tumor stage and metabolic profiles was assessed.DesignPresurgery blood and paired VAT and SAT samples during tumor surgery were obtained from 59 CRC patients (tumor stages I-IV) of the ColoCare cohort. Gas chromatography time-of-flight mass spectrometry and liquid chromatography quadrupole time-of-flight mass spectrometry were used to measure 1065 metabolites in adipose tissue (333 identified compounds) and 1810 metabolites in serum (467 identified compounds). Adipose tissue gene expression was measured by using Illumina's HumanHT-12 Expression BeadChips.ResultsCompared with SAT, VAT displayed elevated markers of inflammatory lipid metabolism, free arachidonic acid, phospholipases (PLA2G10), and prostaglandin synthesis-related enzymes (PTGD/PTGS2S). Plasmalogen concentrations were lower in VAT than in SAT, which was supported by lower gene expression of FAR1, the rate-limiting enzyme for ether-lipid synthesis in VAT. Serum sphingomyelin concentrations were inversely correlated (P = 0.0001) with SAT adipose triglycerides. Logistic regression identified lipids in patients' adipose tissues, which were associated with CRC tumor stage.ConclusionsAs one of the first studies, we comprehensively assessed differences in metabolic, lipidomic, and transcriptomic profiles between paired human VAT and SAT and their association with CRC tumor stage. We identified markers of inflammation in VAT, which supports prior evidence regarding the role of visceral adiposity and cancer.

Background Risk factors for cancer-related fatigue are understudied in colorectal cancer. Purpose This study aimed to address this critical gap in the literature by (a) describing changes in colorectal cancer-related fatigue and health behavior (physical activity, sleep problems) and (b) examining if physical activity and sleep problems predict fatigue trajectories from baseline (approximately at the time of diagnosis), to 6- and 12 months after enrollment. Methods Patients participating in the international ColoCare Study completed self-report measures at baseline (approximately time of diagnosis), 6-, and 12 months assessing physical activity using the International Physical Activity Questionnaire (IPAQ) and fatigue and sleep using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30). Mixed-effect models examined changes in physical activity, sleep problems, and fatigue. Cross-lagged panel models examined bidirectional relationships between physical activity or sleep and fatigue across time. Results Colorectal cancer patients (n = 649) had a mean age of 61 ± 13 years. Most were male (59%), non-Hispanic White (91%), diagnosed with Stages III–IV (56%) colon cancer (58%), and treated with surgery (98%). Within-person cross-lagged models indicated higher physical activity at Month 6 was associated with higher fatigue at Month 12 (β = 0.26, p =.016). When stratified by cancer stage (I–II vs. III–IV), the relationship between physical activity at Month 6 and fatigue at Month 12 existed only for patients with advanced cancer (Stages III and IV, β = 0.43, p =.035). Cross-lagged associations for sleep and fatigue from baseline to Month 6 were only observed in patients with Stages III or IV cancer, however, there was a clear cross-sectional association between sleep problems and fatigue at baseline and Month 6. Conclusions Within-person and cross-lagged association models suggest fatiguability may become increasingly problematic for patients with advanced colorectal cancer the first year after diagnosis. In addition, sleep problems were consistently associated with higher fatigue in the first year, regardless of cancer stage. Trial registration The international ColoCare Study was registered on clinicaltrials.gov, NCT02328677, in December 2014. [ABSTRACT FROM AUTHOR]