Matty P. Weijenberg

Summary: Background: Sugar sweetened beverages (SSBs), artificially sweetened beverages (ASBs), and fruit and vegetable juices are consumed worldwide, yet their associations with cancer remain unclear. Methods: Within World Cancer Research Fund International’s Global Cancer Update Programme (CUP Global), we conducted a systematic review by searching PubMed and Embase until September 2024 for cohort studies of SSBs, ASBs, and juices and cancer risk. Meta-analyses were conducted to calculate the relative risks (RRs) and 95% CIs per 1 serving/day (355 mL for SSBs/ASBs; 177 mL for juices). Evidence was graded by the CUP Global Expert Panel. The CUP Global standard protocol was registered at: https://osf.io/7utbm/ . Findings: We identified 158 publications from 51 cohorts. There was evidence of a probable causal positive association for SSBs, including carbonated SSBs, with pancreatic cancer incidence (RR 1.09 [95% CI 1.01–1.16]; I ² =8%, n=18 studies), and for SSBs with colorectal cancer incidence (RR 1.07 [95% CI 1.00–1.14]; I ² =41%, n=13). Limited suggestive evidence supported positive associations of SSBs with ovarian (RR 1.61 [95%CI 1.03–2.53]; I ² =0%, n=2), endometrial (RR 1.21 [95%CI 1.03-1.42]; I ² =0%, n=3), and postmenopausal breast cancer incidence (RR 1.05 [95%CI 1.00-1.10] ; I ² =0%, n=6), and of carbonated ASBs with leukaemia incidence (RR 1.29 [95%CI 1.01-1.64]; I ² =0%, n=2). There was evidence of a probable causal positive association for orange juice with different types of skin cancer including melanoma (RR 1.21 [95%CI 1.08-1.34]; I ² =0%, n=4), and basal (RR 1.12 [95%CI 1.06-1.17]; I ² =46%, n=2) and squamous cell carcinoma (RR 1.13 [95%CI 1.04-1.24]; I ² =0%, n=2). An interactive evidence platform is available at: https://teacup.cc.ic.ac.uk/soft-drinks-cancer.html . Interpretation: This review provides evidence supporting probable causal associations of SSBs with pancreatic and colorectal cancers, and of orange juice with skin cancers, with additional suggestive evidence for SSBs with other obesity-related cancers, extending concerns about sugary drink consumption beyond cardiometabolic health to cancer risk. Funding: World Cancer Research Fund network of charities (American Institute for Cancer Research; World Cancer Research Fund; Wereld Kanker Onderzoek Fonds).

Summary: Background: High levels of sedentary behaviour are an emerging global public health concern, but its impact on cancer risk remains unclear. Methods: Within the Global Cancer Update Programme (CUP Global), we systematically searched the literature in PubMed and Embase until September 2024 for observational cohort studies on sedentary behaviour and adult cancer risk. Using dose-response meta-analyses, we investigated sedentary behaviour domains (total, occupational, recreational, transportation, and/or other) and dimensions (duration, frequency), and additionally pooled across domains. The quality of evidence was graded by the CUP Global Expert Panel (protocol registration: https://osf.io/7utbm/ ). Findings: We identified 62 publications from 27 cohorts comprising 162,902 incident cancer cases across 19 anatomical sites. There was evidence for a probable causal positive association between sedentary time (mixed definitions) and breast (RR _{per 2 hours/day} =1.03; 95%CI=1.02–1.05; I ² =10%; n=11 studies) and colon (RR=1.05; 95%CI=1.03–1.07; I ² =0%; n=9) cancer risk, and between television watching time and colon cancer risk (RR _{per 2 hours/day} =1.08; 95%CI=1.05–1.11; I ² =0%; n=6). Limited suggestive evidence supported positive associations between sedentary time (mixed definitions) and lung (RR=1.04; 95%CI=1.00–1.09; I ² =69%; n=7), ovarian (RR=1.06; 95%CI=1.01–1.10; I ² =0%; n=7), premenopausal (RR=1.03; 95%CI=0.99–1.08; I ² =20%; n=7) and postmenopausal breast (RR=1.02; 95%CI=1.00–1.04; I ² =7%; n=11), and colorectal (RR=1.02; 95%CI=1.00–1.04; I ² =47%; n=11) cancers, and between occupational sitting time and breast (RR _{per 2 hours/day} =1.05; 95%CI=1.01–1.09; I ² =0%; n=4) and colon (RR=1.08; 95%CI=1.02–1.15; I ² =28%; n=2) cancers. An interactive evidence platform is available at: https://teacup.cc.ic.ac.uk/sedentary-behaviour-cancer.html . Interpretation: Evidence supports that prolonged sedentary behaviour is probably a cause of breast and colon cancers, while limited suggestive evidence supports positive associations for several other exposure–cancer pairs, including lung and ovarian cancers. This evidence should lead to revised cancer prevention recommendations. Future research should focus on device-based exposure assessments, repeated measurements, exposure substitution models, inclusion of diverse populations and investigation of biological mechanisms. Funding: World Cancer Research Fund network of charities (American Institute for Cancer Research; World Cancer Research Fund; Wereld Kanker Onderzoek Fonds).

Supplementary Figure from Longitudinal Associations between Inflammatory Markers and Fatigue up to Two Years after Colorectal Cancer Treatment

Supplementary Table from Longitudinal Associations between Inflammatory Markers and Fatigue up to Two Years after Colorectal Cancer Treatment

Supplementary Figure from Longitudinal Associations between Inflammatory Markers and Fatigue up to Two Years after Colorectal Cancer Treatment

Supplementary Table from Longitudinal Associations between Inflammatory Markers and Fatigue up to Two Years after Colorectal Cancer Treatment

Background:Fatigue is often reported by colorectal cancer survivors and largely impacts their quality of life. Inflammation has been linked to fatigue mainly in patients with breast cancer. Therefore, we investigated how inflammation is longitudinally associated with fatigue in colorectal cancer survivors, up to 2 years posttreatment.Methods:A total of 257 patients from the ongoing Energy for life after ColoRectal cancer cohort study were included in the analysis. Plasma levels of IL6, IL8, IL10, TNFα, high-sensitivity C-reactive protein (hsCRP), and fatigue were measured at 6 weeks, 6, 12, and 24 months posttreatment. Fatigue was measured through the validated Checklist Individual Strength (CIS; total, 20–140), consisting of four subscales – subjective fatigue (8–56), motivation (4–28), physical activity (3–21), and concentration (5–35), and the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 fatigue subscale (0–100). Linear mixed-models were used to assess the confounder-adjusted longitudinal associations between inflammatory markers and overall fatigue along with the subscales.Results:Mean levels of CIS fatigue decreased from 62.9 at 6 weeks to 53.0 at 24 months. In general, levels of inflammatory markers also decreased over time. No statistically significant longitudinal associations were found between IL6, IL8, IL10, TNFα, and fatigue. Higher levels of hsCRP were associated with more CIS fatigue (β per SD 3.21, 95% confidence interval (CI), 1.42–5.01) and EORTC fatigue (β 2.41, 95% CI, 0.72–4.10).Conclusions:Increased levels of hsCRP are longitudinally associated with more posttreatment fatigue in colorectal cancer survivors.Impact:These findings suggest that low-grade inflammation may play a role in fatigue reported by colorectal cancer survivors up to 2 years posttreatment.

Supplementary Figure from Longitudinal Associations between Inflammatory Markers and Fatigue up to Two Years after Colorectal Cancer Treatment

Supplementary data from Energy Balance–Related Factors and Risk of Colorectal Cancer Expressing Different Levels of Proteins Involved in the Warburg Effect