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; Ptrend = .005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82-0.98; Ptrend = .009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83-1.00; Ptrend = .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; Ptrend = .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; Ptrend < .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 (Pheterogeneity = .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.
METHODS: We conducted a nested case-control study in a cohort of 519 978 men and women aged 25 to 70 years followed from 1992 to 2003. A total of 713 incident colon cancer cases were matched, using risk-set sampling, to 713 controls on age, sex, study centre, fasting status and hormonal therapy use. The amount of total physical activity during the past year was expressed in metabolic equivalent of task [MET]-h/week. Anthropometric measurements and blood samples were collected at study baseline.
RESULTS: High physical activity was associated with a lower risk of colon cancer: relative risk ≥91 MET-h/week vs <91 MET-h/week = 0.75 [95% confidence interval (CI): 0.57 to 0.96]. In mediation analyses, this association was accounted for by waist circumference: proportion explained effect (PEE) = 17%; CI: 4% to 52%; and the biomarkers soluble leptin receptor (sOB-R): PEE = 15%; 95% CI: 1% to 50% and 5-hydroxyvitamin D (25[OH]D): PEE = 30%; 95% CI: 12% to 88%. In combination, these factors explained 45% (95% CI: 20% to 125%) of the association. Beyond waist circumference, sOB-R and 25[OH]D additionally explained 10% (95% CI: 1%; 56%) and 23% (95% CI: 6%; 111%) of the association, respectively.
CONCLUSIONS: Promoting physical activity, particularly outdoors, and maintaining metabolic health and adequate vitamin D levels could represent a promising strategy for colon cancer prevention.