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 pksE 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 pksE 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 pksE coli (P = .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 = 0.001) for pksE coli-high tumors, 1.22 (0.57-2.63) for pksE coli-low tumors, and 1.10 (0.85-1.42) for pksE coli-negative tumors. The pksE 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 pksE coli, supporting a potential link between diet, the intestinal microbiota, and colorectal carcinogenesis.