Diets That Promote Colon Inflammation Associate With Risk of Colorectal Carcinomas That Contain Fusobacterium nucleatum

Li Liu, Fred K. Tabung, Xuehong Zhang, Jonathan A. Nowak, Zhi Rong Qian, Tsuyoshi Hamada, Daniel Nevo, Susan Bullman, Kosuke Mima, Keisuke Kosumi, Annacarolina da Silva, Mingyang Song, Yin Cao, Tyler S. Twombly, Yan Shi, Hongli Liu, Mancang Gu, Hideo Koh, Wanwan Li, Chunxia DuYang Chen, Chenxi Li, Wenbin Li, Raaj S. Mehta, Kana Wu, Molin Wang, Aleksander D. Kostic, Marios Giannakis, Wendy S. Garrett, Curtis Hutthenhower, Andrew T. Chan, Charles S. Fuchs, Reiko Nishihara, Shuji Ogino*, Edward L. Giovannucci

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background & Aims: Specific nutritional components are likely to induce intestinal inflammation, which is characterized by increased levels of interleukin 6 (IL6), C-reactive protein (CRP), and tumor necrosis factor–receptor superfamily member 1B (TNFRSF1B) in the circulation and promotes colorectal carcinogenesis. The inflammatory effects of a diet can be estimated based on an empiric dietary inflammatory pattern (EDIP) score, calculated based on intake of 18 foods associated with plasma levels of IL6, CRP, and TNFRSF1B. An inflammatory environment in the colon (based on increased levels of IL6, CRP, and TNFRSF1B in peripheral blood) contributes to impairment of the mucosal barrier and altered immune cell responses, affecting the composition of the intestinal microbiota. Colonization by Fusobacterium nucleatum has been associated with the presence and features of colorectal adenocarcinoma. We investigated the association between diets that promote inflammation (based on EDIP score) and colorectal cancer subtypes classified by level of F nucleatum in the tumor microenvironment. Methods: We calculated EDIP scores based on answers to food frequency questionnaires collected from participants in the Nurses’ Health Study (through June 1, 2012) and the Health Professionals Follow-up Study (through January 31, 2012). Participants in both cohorts reported diagnoses of rectal or colon cancer in biennial questionnaires; deaths from unreported colorectal cancer cases were identified through the National Death Index and next of kin. Colorectal tumor tissues were collected from hospitals where the patients underwent tumor resection and F nucleatum DNA was quantified by a polymerase chain reaction assay. We used multivariable duplication-method Cox proportional hazard regression to assess the associations of EDIP scores with risks of colorectal cancer subclassified by F nucleatum status. Results: During 28 years of follow-up evaluation of 124,433 participants, we documented 951 incident cases of colorectal carcinoma with tissue F nucleatum data. Higher EDIP scores were associated with increased risk of F nucleatum–positive colorectal tumors (Ptrend =.03); for subjects in the highest vs lowest EDIP score tertiles, the hazard ratio for F nucleatum–positive colorectal tumors was 1.63 (95% CI, 1.03–2.58). EDIP scores did not associate with F nucleatum–negative tumors (Ptrend =.44). High EDIP scores associated with proximal F nucleatum–positive colorectal tumors but not with proximal F nucleatum–negative colorectal tumors (Pheterogeneity =.003). Conclusions: Diets that may promote intestinal inflammation, based on EDIP score, are associated with increased risk of F nucleatum–positive colorectal carcinomas, but not carcinomas that do not contain these bacteria. These findings indicate that diet-induced intestinal inflammation alters the gut microbiome to contribute to colorectal carcinogenesis; nutritional interventions might be used in precision medicine and cancer prevention.

Original languageEnglish
Pages (from-to)1622-1631.e3
JournalClinical Gastroenterology and Hepatology
Issue number10
StatePublished - Oct 2018
Externally publishedYes


FundersFunder number
Bennett Family Fund
National Colorectal Cancer Research Alliance
National Institutes of HealthK07 CA188126, R35 CA197735, U01 CA167552, K24 DK098311, R01 CA137178, K99 CA207736, K07 CA190673, P01 CA55075, R01 CA118553, R01 CA151993, P50 CA127003, R01 CA169141, UM1 CA186107
American Association for Cancer Research
National Cancer InstituteP01CA087969
Entertainment Industry Foundation
Dana-Farber Cancer Institute
Dana-Farber/Harvard Cancer Center
Uehara Memorial Foundation
Japan Society for the Promotion of Science81402016
National Natural Science Foundation of China81302491
Huazhong University of Science and Technology
China Scholarship Council
Natural Science Foundation of Beijing Municipality7152140
Beijing Nova ProgramXXJH2015B098
Mochida Memorial Foundation for Medical and Pharmaceutical Research


    • Immunity
    • Microsatellite Instability
    • Nutrition
    • Red Meat


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