Purpose of Review In this review, we describe molecular pathological epidemiology (MPE) studies from around the world that have studied diet and/or lifestyle factors in relation to molecular markers of (epi)genetic pathways in colorectal cancer (CRC), and explore future perspectives in this realm of research. The main focus of this review is diet and lifestyle factors for which there is evidence for an association with CRC as identified by the World Cancer Research Fund reports. In addition, we review promising hypotheses, that warrant consideration in future studies. Recent Findings Associations between molecular characteristics of CRC have been published in relation to smoking, alcohol consumption; body mass index (BMI); waist:hip ratio; adult attained height; physical activity; early life energy restriction; dietary acrylamide, fiber, fat, methyl donors, omega 3 fatty acids; meat, including total protein, processed meat, and heme iron; and fruit and vegetable intake. Summary MPE studies help identify where associations between diet, lifestyle, and CRC risk may otherwise be masked and also shed light on how timing of exposure can influence etiology. Sample size is often an issue, but this may be addressed in the future by pooling data.

Sedentary behavior (sitting/lying at low energy expenditure while awake) is emerging as an important risk factor that may compromise the health-related quality of life (HRQoL) of colorectal cancer (CRC) survivors. We examined associations of sedentary time with HRQoL in CRC survivors, 2-10 years post-diagnosis. In a cross-sectional study, stage I-III CRC survivors (n = 145) diagnosed (2002-2010) at Maastricht University Medical Center+, the Netherlands, wore the thigh-mounted MOX activity monitor 24 h/day for seven consecutive days. HRQoL outcomes were assessed by validated questionnaires (EORTC QLQ-C30, WHODAS II, Checklist Individual Strength, and Hospital Anxiety and Depression Scale). Confounder-adjusted linear regression models were used to estimate associations with HRQoL outcomes of MOX-derived total and prolonged sedentary time (in prolonged sedentary bouts ≥ 30 min), and usual sedentary bout duration, corrected for waking wear time. On average, participants spent 10.2 h/day sedentary (SD, 1.6), and 4.5 h/day in prolonged sedentary time (2.3). Mean usual sedentary bout duration was 27.3 min (SD, 16.8). Greater total and prolonged sedentary time, and longer usual sedentary bout duration were associated with significantly (P < 0.05) lower physical functioning, and higher disability and fatigue scores. Greater prolonged sedentary time and longer usual sedentary bout duration also showed significant associations with lower global quality of life and role functioning. Associations with distress and social functioning were non-significant. Sedentary time was cross-sectionally associated with poorer HRQoL outcomes in CRC survivors. Prospective studies are needed to investigate whether sedentary time reduction is a potential target for lifestyle interventions aiming to improve the HRQoL of CRC survivors.

Background How body size influences risk of molecular subtypes of colorectal cancer (CRC) is unclear. We investigated whether measures of anthropometry differentially influence risk of tumours according to BRAF c.1799T>A p.V600E mutation (BRAF) and microsatellite instability (MSI) status. Methods Data from The Netherlands Cohort Study (n = 120 852) and Melbourne Collaborative Cohort Study (n = 40 514) were pooled and included 734 and 717 colorectal cancer cases from each study, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) for body mass index (BMI), waist measurement and height were calculated and compared for subtypes defined by BRAF mutation and MSI status, measured from archival tissue. Results Results were consistent between studies. When pooled, BMI modelled in 5 kg/m² increments was positively associated with BRAF wild-type (HR: 1.16, 95% CI: 1.08–1.26) and MS-stable tumours (HR: 1.15, 95% CI: 1.06–1.24). Waist measurement was also associated with BRAF wild-type (highest vs lowest quartile, HR: 1.59, 95% CI: 1.33–1.90) and MS-stable tumours (highest vs lowest quartile HR: 1.68, 95% CI: 1.31–2.15). The HRs for BRAF mutation tumours and MSI tumours were smaller and non-significant, but differences between the HRs by tumour subtypes were not significant. Height, modelled per 5-cm increase, was positively associated with BRAF wild-type and BRAF mutation tumours, but the HR was greater for tumours with a BRAF mutation than BRAF wild-type (HR: 1.23, 95% CI: 1.11–1.37, P_{heterogeneity} = 0.03). Similar associations were observed with respect to height and MSI tumours (HR: 1.26, 95% CI: 1.13–1.40, P_{heterogeneity} = 0.02). Conclusions Generally, overweight increases the risk of CRC. Taller individuals have an increased risk of developing a tumour with a BRAF mutation or MSI.

The 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Third Expert Report, including studies up to 2015, determined 'limited-no conclusion' evidence on dietary patterns and colorectal cancer (CRC) risk due to insufficient data and varying pattern definitions. This updated review synthesized literature on dietary patterns and CRC risk/mortality. PubMed and Embase were searched through 31 March 2023 for randomized controlled trials (RCTs) and prospective cohort studies on adulthood dietary patterns. Patterns were categorized by derivation method: a priori, a posteriori, or hybrid; and were then descriptively reviewed in relation to the primary outcomes: CRC risk or mortality. The Global Cancer Update Programme Expert Committee and Expert Panel independently graded the evidence on the likelihood of causality using pre-defined criteria. Thirty-two dietary scores from 53 observational studies and three RCTs were reviewed. 'Limited-suggestive' evidence was concluded for higher alignment with a priori-derived patterns: Mediterranean, healthful plant-based index, Healthy Eating Index (HEI)/alternate HEI (AHEI), and Dietary Approaches to Stop Hypertension (DASH) in relation to lower CRC risk. Common features across these diets included high plant-based food intake and limited red/processed meat. Hybrid-derived patterns: the Empirical Dietary Pattern for Hyperinsulinemia (EDIH) and Empirical Dietary Inflammatory Pattern (EDIP) showed 'strong-probable' evidence for increased CRC risk. Evidence for a priori-derived low-fat dietary interventions and a posteriori-derived patterns was graded as 'limited-no conclusion'. By cancer subsite, higher alignment with Mediterranean diet showed 'limited-suggestive' evidence for lower rectal cancer risk, and with HEI/AHEI and DASH showed 'limited-suggestive' evidence for lower colon and rectal cancer risks. EDIH and EDIP showed 'strong-probable' evidence for increased colon cancer risks. All exposure-mortality pairs and other pattern-outcome associations were graded as 'limited-no conclusion'. This review highlights the role of dietary patterns in CRC risk/mortality, providing insights for future research and public health strategies. This review was registered at PROSPERO as CRD42022324327 (Link: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022324327).

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

While healthy dietary and lifestyle factors have been individually linked to lower colorectal cancer (CRC) risks, recommendations for whole diet-lifestyle patterns remained unestablished due to limited studies and inconsistent pattern definitions. This updated review synthesized literature on dietary-lifestyle patterns and CRC risk/mortality. PubMed and Embase were searched through 31 March 2023 for randomized controlled trials and prospective cohort studies examining adulthood dietary patterns combined with modifiable lifestyle factors such as adiposity, smoking, alcohol consumption, physical activity, and/or others. Patterns were categorized by derivation methods: a priori, a posteriori, and a hybrid combining both; and were then descriptively reviewed for the primary outcomes: CRC risk or mortality. The Global Cancer Update Programme Expert Committee and Expert Panel independently graded the evidence on the likelihood of causality using pre-defined grading criteria. Thirty-three observational studies were reviewed. 'Strong-probable' evidence was concluded for higher levels of alignment with the a priori-derived World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) recommendations score and lower CRC risk; and 'limited-suggestive' evidence for the American Cancer Society guidelines and Healthy Lifestyle Index with lower CRC risk (mainly due to concerns about risk of bias for confounding). A posteriori-derived patterns lack firm evidence (only one study). 'Strong-probable' evidence was concluded for higher levels of alignment with the Empirical Lifestyle Index for Hyperinsulinemia hybrid pattern and higher CRC risk. By cancer subsite, only the WCRF/AICR recommendations score showed 'strong-probable' evidence with lower colon cancer risk. All exposure-mortality pairs were graded 'limited-no conclusion'. The evidence for other pattern-outcome associations was graded as 'limited-no conclusion'. Adopting a healthy pattern of diet, maintaining a healthy weight, staying physically active, and embracing health-conscious habits, such as avoiding tobacco and moderating alcohol, are collectively associated with a lower CRC risk. Healthy lifestyle habits are key to primary CRC prevention.