Western-style Diet, pks Island-Carrying Escherichia coli, and Colorectal Cancer: Analyses from Two Large Prospective Cohort Studies

Evidence supports a carcinogenic role of Escherichia coli carrying the polyketide synthase (pks) island that encodes enzymes for colibactin biosynthesis. We hypothesized that the association of western-style diet (rich in red and processed meat) with colorectal cancer incidence might be stronger for tumors containing higher amounts of pks+ E. coli.
Western diet score was calculated using food frequency questionnaire data obtained every four years during follow-up of 134,775 participants in two U.S.-wide prospective cohort studies. Using quantitative polymerase chain reaction, we measured pks+ E. coli DNA in 1,175 tumors among 3,200 incident colorectal cancer cases that had occurred during the follow-up. We utilized the 3,200 cases and inverse probability weighting (to adjust for selection bias due to tissue availability), integrated in multivariable-adjusted duplication-method Cox proportional hazards regression analyses.

The association of the western diet score with colorectal cancer incidence was stronger for tumors containing higher levels of pks+ E. coli (Pheterogeneity = 0.014). Multivariable-adjusted hazard ratios (with 95% confidence interval) for the highest (vs. lowest) tertile of the western diet score were 3.45 (1.53-7.78) (Ptrend = 0.001) for pks+ E. coli-high tumors, 1.22 (0.57-2.63) for pks+ E. coli-low tumors, and 1.10 (0.85-1.42) for pks+ E. coli-negative tumors. The pks+ E. coli level was associated with lower disease stage but not with tumor location, microsatellite instability, or BRAF, KRAS, or PIK3CA mutations.

Western-style diet is associated with higher incidence of colorectal cancer containing abundant pks+ E. coli, supporting a potential link between diet, the intestinal microbiota, and colorectal carcinogenesis.