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The underlying biological mechanisms causing persistent fatigue complaints after colorectal cancer treatment need further investigation. We investigated longitudinal associations of circulating concentrations of 138 metabolites with total fatigue and subdomains of fatigue between 6 weeks and 2 years after colorectal cancer treatment. Among stage I‐III colorectal cancer survivors (n = 252), blood samples were obtained at 6 weeks, and 6, 12 and 24 months posttreatment. Total fatigue and fatigue subdomains were measured using a validated questionnaire. Tandem mass spectrometry was applied to measure metabolite concentrations (BIOCRATES AbsoluteIDQp180 kit). Confounder‐adjusted longitudinal associations were analyzed using linear mixed models, with false discovery rate (FDR) correction. We assessed interindividual (between‐participant differences) and intraindividual longitudinal associations (within‐participant changes over time). In the overall longitudinal analysis, statistically significant associations were observed for 12, 32, 17 and three metabolites with total fatigue and the subscales "fatigue severity," "reduced motivation" and "reduced activity," respectively. Specifically, higher concentrations of several amino acids, lysophosphatidylcholines, diacylphosphatidylcholines, acyl‐alkylphosphatidylcholines and sphingomyelins were associated with less fatigue, while higher concentrations of acylcarnitines were associated with more fatigue. For "fatigue severity," associations appeared mainly driven by intraindividual associations, while for "reduced motivation" stronger interindividual associations were found. We observed longitudinal associations of several metabolites with total fatigue and fatigue subscales, and that intraindividual changes in metabolites over time were associated with fatigue severity. These findings point toward inflammation and an impaired energy metabolism due to mitochondrial dysfunction as underlying mechanisms. Mechanistic studies are necessary to determine whether these metabolites could be targets for intervention. [ABSTRACT FROM AUTHOR]

High‐grade glioma (HGG) is associated with poor prognosis. Drug repurposing evolves as new modality to improve standard therapy. The antidiabetic drug metformin has been found to inhibit glioma cell growth in vitro and in vivo. The aim of the present retrospective cohort study was to evaluate the survival of patients with HGG with or without treatment with metformin, based on a large cohort of a cancer registry. The analysis included 1,093 patients with HGG diagnosed between 1998 and 2013 from the population‐based clinical cancer registry Regensburg (Germany), which covers 2.1 Mio inhabitants and 98% of all cancer diagnoses. We performed multivariable adjusted Cox‐regression analyses. Hazard Ratios (HRs) with 95% Confidence Intervals (CIs) for overall survival (OS) and progression‐free survival (PFS) of patients with HGG with or without treatment with metformin were obtained. Use of metformin was associated with a significantly better overall and progression‐free survival of patients with WHO grade III glioma (HR for OS = 0.30; 95% CI = 0.11–0.81, HR for PFS = 0.29; 95% CI = 0.11–0.78), while there were no significant relations with OS (HR = 0.83; 95% CI = 0.57–1.20) or PFS (HR = 0.85; 95% CI = 0.59–1.22) in patients with WHO grade IV glioma. In conclusion, use of metformin is associated with better overall and progression‐free survival of patients with WHO grade III. Possible underlying mechanisms include the higher prevalence of IDH mutations in WHO grade III glioma, which might sensitize to the metabolic drug metformin. What's new? The oral diabetes drug metformin seems to boost survival of high grade glioma (HGG). In this study, the authors examined metformin use in a cohort of over 1,000 HGG patients. Patients with WHO grade III glioma had better survival if they were taking metformin, while no improvement in outcomes was associated with other diabetes medications, including sulfonylureas or insulin. No benefit was observed in patients with WHO grade IV cancers. The authors propose that the survival benefit may be linked to IDH mutations, which often occur in stage III but not stage IV gliomas. [ABSTRACT FROM AUTHOR]

Anthropometric measures relating to body size, weight and composition are increasingly being associated with cancer risk and progression. Whilst practical in epidemiologic research, where population-level associations with disease are revealed, it is important to be aware that such measures are imperfect markers of the internal physiological processes that are the actual correlates of cancer development. Body mass index (BMI), the most commonly used marker for adiposity, may mask differences between lean and adipose tissue, or fat distribution, which varies across individuals, ethnicities, and stage in the lifespan. Other measures, such as weight gain in adulthood, waist circumference and waist-to-hip ratio, contribute information on adipose tissue distribution and insulin sensitivity. Single anthropometric measures do not capture maturational events, including the presence of critical windows of susceptibility ( i.e., age of menarche and menopause), which presents a challenge in epidemiologic work. Integration of experimental research on underlying dynamic genetic, hormonal, and other non-nutritional mechanisms is necessary for a confident conclusion of the overall evidence in cancer development and progression. This article discusses the challenges confronted in evaluating and interpreting the current evidence linking anthropometric factors and cancer risk as a basis for issuing recommendations for cancer prevention. [ABSTRACT FROM AUTHOR]

Few studies have examined exercise in relation to risk of renal cell cancer. We examined the association between leisure-time and occupational physical activity and renal cell cancer in a cohort of 29,133 male smokers 50-69 years of age in the Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study. Physical activity was assessed at baseline using a self-administered questionnaire that inquired about usual level of physical activity during leisure-time and at work during the past year. Cox proportional hazards modeling was used to adjust simultaneously for known or suspected risk factors for renal cell cancer. During 12 years (354,407 person-years) of follow-up, 210 incident cases of renal cell cancer were identified. In age-adjusted analysis, the RRs of renal cell cancer in increasing categories of leisure-time physical activity (light, moderate and heavy) were 1.0, 0.89 (95% CI = 0.67-1.17) and 0.38 (95% CI = 0.15-0.94), respectively (p-value for trend = 0.06). After adjustment for body mass index, energy intake, smoking, hypertension, education and fruit and vegetable intake, the multivariate RRs of renal cell cancer in increasing categories of leisure-time physical activity (light, moderate and heavy), were 1.0, 0.89 (95% CI = 0.66-1.19), and 0.46 (95% CI = 0.18-1.13) (p-value for trend = 0.12). Occupational physical activity was unrelated to renal cell cancer risk. These data suggest that recreational physical activity may play a role in the prevention of renal cell cancer in men., (Copyright 2003 Wiley-Liss, Inc.)