Dietary Patterns and Risk of Colorectal Cancer Subtypes Classified by Fusobacterium nucleatum in Tumor Tissue

Authors

Raaj S. Mehta, Massachusetts General Hospital and Harvard Medical School
Reiko Nishihara, Brigham and Women’s Hospital and Harvard Medical School & Broad Institute of Massachusetts Institute of Technology and Harvard University & Harvard T.H. Chan School of Public Health & Dana-Farber Cancer Institute and Harvard Medical School
Yin Cao, Massachusetts General Hospital and Harvard Medical School & Harvard T.H. Chan School of Public Health
Mingyang Song, Massachusetts General Hospital and Harvard Medical School & Harvard T.H. Chan School of Public Health
Kosuke Mima, Dana-Farber Cancer Institute and Harvard Medical School
Zhi Rong Qian, Dana-Farber Cancer Institute and Harvard Medical School
Jonathan A. Nowak, Brigham and Women’s Hospital and Harvard Medical School
Keisuke Kosumi, Dana-Farber Cancer Institute and Harvard Medical School
Tsuyoshi Hamada, Dana-Farber Cancer Institute and Harvard Medical School
Yohei Masugi, Dana-Farber Cancer Institute and Harvard Medical School
Susan Bullman, Dana-Farber Cancer Institute and Harvard Medical School
David A. Drew, Massachusetts General Hospital and Harvard Medical School
Aleksandar D. Kostic, Broad Institute of Massachusetts Institute of Technology and Harvard University
Teresa T. Fung, Simmons College
Wendy S. Garrett, Broad Institute of Massachusetts Institute of Technology and Harvard University & Dana-Farber Cancer Institute and Harvard Medical School & Harvard T.H. Chan School of Public Health
Curtis Huttenhower, Harvard T.H. Chan School of Public Health
Kana Wu, Harvard T.H. Chan School of Public Health
Jeffrey A. Meyerhardt, Dana-Farber Cancer Institute and Harvard Medical School
Xuehong Zhang, Brigham and Women’s Hospital and Harvard Medical School
Walter C. Willett, Harvard T.H. Chan School of Public Health & Brigham and Women’s Hospital and Harvard Medical School
Edward L. Giovannucci, Harvard T.H. Chan School of Public Health & Brigham and Women’s Hospital and Harvard Medical School
Charles S. Fuchs, Dana-Farber Cancer Institute and Harvard Medical School & Brigham and Women’s Hospital and Harvard Medical School
Andrew T. Chan, Massachusetts General Hospital and Harvard Medical School & Broad Institute of Massachusetts Institute of Technology and Harvard University & Brigham and Women’s Hospital and Harvard Medical School
Shuji Ogino, Brigham and Women’s Hospital and Harvard Medical School & Dana-Farber Cancer Institute and Harvard Medical SchoolFollow

Document Type

Article

Date of this Version

7-1-2018

Citation

JAMA Oncol. 2017 July 01; 3(7): 921–927. doi:10.1001/jamaoncol.2016.6374.

Abstract

Importance—Fusobacterium nucleatum appears to play a role in colorectal carcinogenesis through suppression of host immune response to tumor. Evidence also suggests that diet influences intestinal F. nucleatum. However, the role of F. nucleatum in mediating the relationship between diet and the risk of colorectal cancer is unknown.

Objective—To test the hypothesis that the associations of prudent diets (rich in whole grains and dietary fiber) and Western diets (rich in red and processed meat, refined grains, and desserts) with colorectal cancer risk may differ according to the presence of F. nucleatum in tumor tissue.

Design—Prospective cohort study.

Setting—The Nurses’ Health Study (1980–2012) and the Health Professionals Follow-up Study (1986–2012).

Participants—121,700 US female nurses and 51,529 US male health professionals aged 30 to 55 years and 40 to 75 years, respectively, at enrollment.

Exposures—Prudent and Western dietary patterns.

Main Outcomes and Measures—Incidence of colorectal carcinoma subclassified by F. nucleatum status in tumor tissue, determined by quantitative polymerase chain reaction.

Results—We documented 1,019 incident colon and rectal cancer cases with available F. nucleatum data among predominantly white 137,217 individuals over 26–32 years of follow-up encompassing 3,643,562 person-years. The association of prudent diet with colorectal cancer significantly differed by tissue F. nucleatum status (Pheterogeneity = .01). Prudent diet score was associated with a lower risk of F. nucleatum-positive cancers [Ptrend = .003; multivariable hazard ratio of 0.43 (95% confidence interval 0.25–0.72) for the highest vs. the lowest prudent score quartile], but not with F. nucleatum-negative cancers (Ptrend = .47). Dietary component analyses suggested possible differential associations for the cancer subgroups according to intakes of dietary fiber (Pheterogeneity = .02). There was no significant heterogeneity between the subgroups according to Western dietary pattern scores (Pheterogeneity = .23).

Conclusions and Relevance—Prudent diets rich in whole grains and dietary fiber are associated with a lower risk for F. nucleatum-positive colorectal cancer but not F. nucleatum-negative cancer, supporting a potential role for intestinal microbiota in mediating the association between diet and colorectal neoplasms.