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

Background & Aims: Evidence supports a carcinogenic role of Escherichia coli carrying the pks island that encodes enzymes for colibactin biosynthesis. We hypothesized that the association of the 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. Methods: Western diet score was calculated using food frequency questionnaire data obtained every 4 years during follow-up of 134,775 participants in 2 United States-wide prospective cohort studies. Using quantitative polymerase chain reaction, we measured pks⁺ E coli DNA in 1175 tumors among 3200 incident colorectal cancer cases that had occurred during the follow-up. We used the 3200 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. Results: The association of the Western diet score with colorectal cancer incidence was stronger for tumors containing higher levels of pks⁺ E coli (P_{heterogeneity} = .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) (P_trend = 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. Conclusions: The Western-style diet is associated with a higher incidence of colorectal cancer containing abundant pks⁺ E coli, supporting a potential link between diet, the intestinal microbiota, and colorectal carcinogenesis.