Raaj S Mehta1, Reiko Nishihara2, Yin Cao3, Mingyang Song3, Kosuke Mima4, Zhi Rong Qian4, Jonathan A Nowak5, Keisuke Kosumi4, Tsuyoshi Hamada4, Yohei Masugi4, Susan Bullman4, David A Drew1, Aleksandar D Kostic6, Teresa T Fung7, Wendy S Garrett8, Curtis Huttenhower9, Kana Wu10, Jeffrey A Meyerhardt4, Xuehong Zhang11, Walter C Willett12, Edward L Giovannucci13, Charles S Fuchs14, Andrew T Chan15, Shuji Ogino16. 1. Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston2Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston. 2. Division of MPE Molecular Pathological Epidemiology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts4Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts5Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge6Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts7Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts8Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts9Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts. 3. Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston2Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston6Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 4. Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts. 5. Division of MPE Molecular Pathological Epidemiology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts4Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. 6. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge. 7. Program in Dietetics, Simmons College, Boston, Massachusetts. 8. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge9Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts11Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts. 9. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 10. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 11. Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. 12. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts12Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. 13. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts7Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts12Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. 14. Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts12Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. 15. Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston2Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston5Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge12Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. 16. Division of MPE Molecular Pathological Epidemiology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts4Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts7Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts9Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts13Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
Abstract
IMPORTANCE: Fusobacterium nucleatum appears to play a role in colorectal carcinogenesis through suppression of the hosts' 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, SETTING, AND PARTICIPANTS: A prospective cohort study was conducted using data from the Nurses' Health Study (June 1, 1980, to June 1, 2012) and the Health Professionals Follow-up Study (June 1, 1986, to June 1, 2012) on a total of 121 700 US female nurses and 51 529 US male health professionals aged 30 to 55 years and 40 to 75 years, respectively (both predominantly white individuals), at enrollment. Data analysis was performed from March 15, 2015, to August 10, 2016. EXPOSURES: Prudent and Western diets. MAIN OUTCOMES AND MEASURES: Incidence of colorectal carcinoma subclassified by F nucleatum status in tumor tissue, determined by quantitative polymerase chain reaction. RESULTS: Of the 173 229 individuals considered for the study, 137 217 were included in the analysis, 47 449 were male (34.6%), and mean (SD) baseline age for men was 54.0 (9.8) years and for women, 46.3 (7.2) years. A total of 1019 incident colon and rectal cancer cases with available F nucleatum data were documented over 26 to 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 (P = .01 for heterogeneity); prudent diet score was associated with a lower risk of F nucleatum-positive cancers (P = .003 for trend; multivariable hazard ratio of 0.43; 95% CI, 0.25-0.72, for the highest vs the lowest prudent score quartile) but not with F nucleatum-negative cancers (P = .47 for trend, the corresponding multivariable hazard ratio of 0.95; 95% CI, 0.77-1.17). There was no significant heterogeneity between the subgroups in relation to Western dietary pattern scores. 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.
IMPORTANCE: Fusobacterium nucleatum appears to play a role in colorectal carcinogenesis through suppression of the hosts' 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, SETTING, AND PARTICIPANTS: A prospective cohort study was conducted using data from the Nurses' Health Study (June 1, 1980, to June 1, 2012) and the Health Professionals Follow-up Study (June 1, 1986, to June 1, 2012) on a total of 121 700 US female nurses and 51 529 US male health professionals aged 30 to 55 years and 40 to 75 years, respectively (both predominantly white individuals), at enrollment. Data analysis was performed from March 15, 2015, to August 10, 2016. EXPOSURES: Prudent and Western diets. MAIN OUTCOMES AND MEASURES: Incidence of colorectal carcinoma subclassified by F nucleatum status in tumor tissue, determined by quantitative polymerase chain reaction. RESULTS: Of the 173 229 individuals considered for the study, 137 217 were included in the analysis, 47 449 were male (34.6%), and mean (SD) baseline age for men was 54.0 (9.8) years and for women, 46.3 (7.2) years. A total of 1019 incident colon and rectal cancer cases with available F nucleatum data were documented over 26 to 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 (P = .01 for heterogeneity); prudent diet score was associated with a lower risk of F nucleatum-positive cancers (P = .003 for trend; multivariable hazard ratio of 0.43; 95% CI, 0.25-0.72, for the highest vs the lowest prudent score quartile) but not with F nucleatum-negative cancers (P = .47 for trend, the corresponding multivariable hazard ratio of 0.95; 95% CI, 0.77-1.17). There was no significant heterogeneity between the subgroups in relation to Western dietary pattern scores. 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.
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