There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS:Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs. RESULTS:Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80-0.96; P trend [ .005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82-0.98; P trend [ .009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83-1.00; P trend [ .016) were inversely associated with CRC incidence.Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78-0.95; P trend [ .010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA was associated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18-1.45; P trend < .001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal colon cancer (P heterogeneity [ .026). CONCLUSIONS:In an analysis of dietary patterns of participants in the EPIC study, we found regular consumption of fish, at recommended levels, to be associated with a lower risk of CRC, possibly through exposure to n-3 LC-PUFA. Levels of n-3 LC-PUFA in plasma were not associated with CRC risk, but there may be differences in risk at different regions of the colon.

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Background Skeletal muscle mass (SMM) loss is common in metastatic colorectal cancer (mCRC) patients and associated with poor clinical outcomes, including increased treatment‐related toxicities and reduced survival. Muscle loss may contribute to reduced health‐related quality of life (HRQoL), including fatigue. Our aim was to study associations between changes in SMM and concomitant changes in patient‐reported HRQoL. Methods This was a secondary analysis of mCRC patients in the CAIRO3 randomized clinical trial who were—after initial treatment—randomized between maintenance treatment with capecitabine plus bevacizumab (CAP‐B) and observation until first disease progression (PD1). Included patients had computed tomography images for SMM quantification, together with HRQoL assessments available at randomization and PD1. Changes in SMM (categorized as >2% loss, stable, and >2% gain) and HRQoL were computed between randomization and PD1. Changes in HRQoL score >10 points were considered clinically relevant. Associations between SMM and HRQoL changes were studied by multiple linear regression models. We also investigated whether associations differed by treatment arm for global health and the 13 other HRQoL subscales. Results Of 221 patients included (mean age 63.5 ± 8.4 years), 24% lost, 27% remained stable, and 49% gained SMM. At randomization, mean global health status was 73.5 ± 15.9 in the CAP‐B arm and 75.1 ± 17.5 in the observation arm ( P = 0.48). A stable or gain in SMM was significantly associated with a clinically relevant improvement in global health status (9.9 and 14.7 points, respectively), compared with patients who lost SMM. From the subscales that did not show significant differences between the two treatment arms, we found significant and clinically relevant associations for stable or gain in SMM with improved role functioning (12.0 and 17.9, respectively) and with less fatigue (−10.0 and −15.0, respectively) and pain (−16.3 for SMM gain). From the subscales that did show significantly different associations with SMM between the two treatment arms, we only found significant results in the observation arm. Here, associations were found for stable or gain in SMM with clinically relevant improved physical (12.4 for SMM gain), cognitive (10.7 and 9.7, respectively), and social functioning (15.5 and 15.6, respectively) as well as reduced appetite loss (−28.5 and −30.7, respectively). Conclusions In mCRC, SMM preservation during CAP‐B and observation treatment is associated with significant and clinically relevant improvements in global health status and multiple functional and symptom scales. Studies are warranted to investigate whether interventions targeting SMM lead to improved HRQoL, fewer symptoms, and better functioning.