There is convincing evidence that high physical activity lowers the risk of colon cancer; however, the underlying biological mechanisms remain largely unknown. We aimed to determine the extent to which body fatness and biomarkers of various biologically plausible pathways account for the association between physical activity and colon cancer.

Polyphenols may play a chemopreventive role in colorectal cancer (CRC); however, epidemiological evidence supporting a role for intake of individual polyphenol classes, other than flavonoids is insufficient. We evaluated the association between dietary intakes of total and individual classes and subclasses of polyphenols and CRC risk and its main subsites, colon and rectum, within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The cohort included 476,160 men and women from 10 European countries. During a mean follow-up of 14 years, there were 5991 incident CRC cases, of which 3897 were in the colon and 2094 were in the rectum. Polyphenol intake was estimated using validated centre/country specific dietary questionnaires and the Phenol-Explorer database. In multivariable-adjusted Cox regression models, a doubling in total dietary polyphenol intake was not associated with CRC risk in women (HRlog2 = 1.06, 95% CI 0.99-1.14) or in men (HRlog2 = 0.97, 95% CI 0.90-1.05), respectively. Phenolic acid intake, highly correlated with coffee consumption, was inversely associated with colon cancer in men (HRlog2 = 0.91, 95% CI 0.85-0.97) and positively associated with rectal cancer in women (HRlog2 = 1.10, 95% CI 1.02-1.19); although associations did not exceed the Bonferroni threshold for significance. Intake of other polyphenol classes was not related to colorectal, colon or rectal cancer risks. Our study suggests a possible inverse association between phenolic acid intake and colon cancer risk in men and positive with rectal cancer risk in women.

Polyphenols have been shown to exert biological activity in experimental models of colon cancer; however, human data linking specific polyphenols to colon cancer is limited. We assessed the relationship between pre-diagnostic plasma polyphenols and colon cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition study. Using high pressure liquid chromatography coupled to tandem mass spectrometry, we measured concentrations of 35 polyphenols in plasma from 809 incident colon cancer cases and 809 matched controls. We used multivariable adjusted conditional logistic regression models that included established colon cancer risk factors. The false discovery rate (qvalues ) was computed to control for multiple comparisons. All statistical tests were two-sided. After false discovery rate correction and in continuous log2 -transformed multivariable models, equol (odds ratio [OR] per log2 -value, 0.86, 95% confidence interval [95%CI]=0.79-0.93; qvalue =0.01) and homovanillic acid (OR per log2 -value, 1.46, 95%CI=1.16-1.84; qvalue =0.02) were associated with colon cancer risk. Comparing extreme fifths, equol concentrations were inversely associated with colon cancer risk (OR=0.61, 95%CI=0.41-0.91, ptrend =0.003), while homovanillic acid concentrations were positively associated with colon cancer development (OR=1.72, 95%CI=1.17-2.53, ptrend <0.0001). No heterogeneity for these associations was observed by sex and across other colon cancer risk factors. The remaining polyphenols were not associated with colon cancer risk. Higher equol concentrations were associated with lower risk, and higher homovanillic acid concentrations were associated with greater risk, of colon cancer. These findings support a potential role for specific polyphenols in colon tumorigenesis. This article is protected by copyright. All rights reserved.

Evidence indicates that gaining weight in adult life is associated with an elevated risk of colorectal cancer; however, biological mechanisms that may explain this association remain unclear. We evaluated the mediation effect of 20 different biomarkers on the relationship between adult weight gain and colorectal cancer, using data from a prospective nested case-control study of 452 incident cases diagnosed between 1992 and 2003 and matched within risk sets to 452 controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The proportions of mediated effects (%) were estimated on the basis of differences in percent effect changes in conditional logistic regression models with and without additional adjustment for individual biomarkers. Greater adult weight gain (≥300 g/year vs. <300 g/year) was associated with a higher risk of colon cancer (multivariable-adjusted relative risk = 1.54, 95% confidence interval: 1.07, 2.24) but not rectal cancer (relative risk = 1.07, 95% confidence interval: 0.68, 1.66). This association was accounted for mostly by attained waist circumference (reduction of 61%) and by the biomarkers soluble leptin receptor (reduction of 43%) and glycated hemoglobin (reduction of 28%). These novel data suggest that the observed association between adult weight gain and colon cancer could be primarily explained by attained abdominal fatness and biomarkers of metabolic dysfunction.

Leakage of bacterial products across the gut barrier may play a role in liver diseases which often precede the development of liver cancer. However, human studies, particularly from prospective settings, are lacking.

The relationship between coffee consumption and mortality in diverse European populations with variable coffee preparation methods is unclear.

Evidence on the association between physical activity and risk of hepatobiliary cancers is inconclusive. We examined this association in the European Prospective Investigation into Cancer and Nutrition cohort (EPIC). We identified 275 hepatocellular carcinoma (HCC) cases, 93 intrahepatic bile duct cancers (IHBCs), and 164 non-gallbladder extrahepatic bile duct cancers (NGBCs) among 467,336 EPIC participants (median follow-up 14.9 years). We estimated cause-specific hazard ratios (HRs) for total physical activity and vigorous physical activity and performed mediation analysis and secondary analyses to assess robustness to confounding (e.g. due to hepatitis virus infection). In the EPIC cohort, the multivariable-adjusted HR of HCC was 0.55 (95% CI 0.38-0.80) comparing active and inactive individuals. Regarding vigorous physical activity, for those reporting >2 hours/week compared to those with no vigorous activity, the HR for HCC was 0.50 (95% CI 0.33-0.76). Estimates were similar in sensitivity analyses for confounding. Total and vigorous physical activity were unrelated to IHBC and NGBC. In mediation analysis, waist circumference explained about 40% and body mass index 30% of the overall association of total physical activity and HCC. These findings suggest an inverse association between physical activity and risk of HCC, which is potentially mediated by obesity.