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

2022; Elsevier BV; Volume: 163; Issue: 4 Linguagem: Inglês

10.1053/j.gastro.2022.06.054

1528-0012

Kota Arima, Rong Zhong, Tomotaka Ugai, Melissa Zhao, Koichiro Haruki, Naohiko Akimoto, Mai Chan Lau, Kazuo Okadome, Raaj S. Mehta, Juha P. Väyrynen, Junko Kishikawa, Tyler S. Twombly, Shanshan Shi, Kenji Fujiyoshi, Keisuke Kosumi, Yoko Ogata, Hideo Baba, Fenglei Wang, Kana Wu, Mingyang Song, Xuehong Zhang, Charles S. Fuchs, Cynthia L. Sears, Walter C. Willett, Edward L. Giovannucci, Jeffrey A. Meyerhardt, Wendy S. Garrett, Curtis Huttenhower, Andrew T. Chan, Jonathan A. Nowak, Marios Giannakis, Shuji Ogino,

Gut microbiota and health

Background & AimsEvidence 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.MethodsWestern 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.ResultsThe association of the Western diet score with colorectal cancer incidence was stronger for tumors containing higher levels of pks+ E coli (Pheterogeneity = .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.ConclusionsThe 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. 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. 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. The association of the Western diet score with colorectal cancer incidence was stronger for tumors containing higher levels of pks+ E coli (Pheterogeneity = .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. 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.