TY - JOUR
T1 - Diets That Promote Colon Inflammation Associate With Risk of Colorectal Carcinomas That Contain Fusobacterium nucleatum
AU - Liu, Li
AU - Tabung, Fred K.
AU - Zhang, Xuehong
AU - Nowak, Jonathan A.
AU - Qian, Zhi Rong
AU - Hamada, Tsuyoshi
AU - Nevo, Daniel
AU - Bullman, Susan
AU - Mima, Kosuke
AU - Kosumi, Keisuke
AU - da Silva, Annacarolina
AU - Song, Mingyang
AU - Cao, Yin
AU - Twombly, Tyler S.
AU - Shi, Yan
AU - Liu, Hongli
AU - Gu, Mancang
AU - Koh, Hideo
AU - Li, Wanwan
AU - Du, Chunxia
AU - Chen, Yang
AU - Li, Chenxi
AU - Li, Wenbin
AU - Mehta, Raaj S.
AU - Wu, Kana
AU - Wang, Molin
AU - Kostic, Aleksander D.
AU - Giannakis, Marios
AU - Garrett, Wendy S.
AU - Hutthenhower, Curtis
AU - Chan, Andrew T.
AU - Fuchs, Charles S.
AU - Nishihara, Reiko
AU - Ogino, Shuji
AU - Giovannucci, Edward L.
N1 - Funding Information:
Funding Supported by National Institutes of Health grants P01 CA87969 (M.J.S.), UM1 CA186107 (M.J.S.), P01 CA55075 (W.C.W.), UM1 CA167552 (W.C.W.), U01 CA167552 (W.C.W. and L.A.M.), R01 CA118553 (C.S.F.), R01 CA169141 (C.S.F.), P50 CA127003 (C.S.F.), R01 CA137178 (A.T.C.), K24 DK098311 (A.T.C.), R01 CA151993 (S.O.), R35 CA197735 (S.O.), K07 CA190673 (R.N.), K07 CA188126 (X.Z.), and K99 CA207736 (F.K.T.); a Nodal Award (S.O.) from the Dana-Farber Harvard Cancer Center; and by grants from The Project P Fund for Colorectal Cancer Research, The Friends of the Dana-Farber Cancer Institute, Bennett Family Fund, the Entertainment Industry Foundation through the National Colorectal Cancer Research Alliance, and American Association for Cancer Research (Stand Up to Cancer Colorectal Cancer Dream Team Translational Research Grant). Also supported by a grant from the National Natural Science Foundation of China no. 81302491, a scholarship grant from the Chinese Scholarship Council, and a fellowship grant from Huazhong University of Science and Technology (L.L.); a fellowship grant from the Uehara Memorial Foundation and by a grant from the Mochida Memorial Foundation for Medical and Pharmaceutical Research (T.H.); by a grant from the Program for Advancing Strategic International Networks to Accelerate the Circulation of Talented Researchers from the Japanese Society for the Promotion of Science (K.K.); and by grants from National Natural Science Foundation of China no. 81402016, Beijing Natural Science Foundation no. 7152140, and Beijing Nova Program XXJH2015B098 (Y.S.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.
Publisher Copyright:
© 2018 AGA Institute
PY - 2018/10
Y1 - 2018/10
N2 - 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.
AB - 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.
KW - Immunity
KW - Microsatellite Instability
KW - Nutrition
KW - Red Meat
UR - http://www.scopus.com/inward/record.url?scp=85053465075&partnerID=8YFLogxK
U2 - 10.1016/j.cgh.2018.04.030
DO - 10.1016/j.cgh.2018.04.030
M3 - Article
C2 - 29702299
AN - SCOPUS:85053465075
VL - 16
SP - 1622-1631.e3
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
SN - 1542-3565
IS - 10
ER -