The Sulfur Microbial Diet and Risk of Colorectal Cancer by Molecular Subtypes and Intratumoral Microbial Species in Adult Men

Authors

Daniel R. Sikavi, Massachusetts General Hospital
Long H. Nguyen, Massachusetts General Hospital
Koichiro Haruki, Brigham and Women's Hospital
Tomotaka Ugai, Brigham and Women's Hospital
Wenjie Ma, Massachusetts General Hospital
Dong D. Wang, Harvard T.H. Chan School of Public Health
Kelsey N. Thompson, Harvard T.H. Chan School of Public Health
Yan Yan, Harvard T.H. Chan School of Public Health
Tobyn Branck, Harvard T.H. Chan School of Public Health
Jeremy E. Wilkinson, Harvard T.H. Chan School of Public Health
Naohiko Akimoto, Brigham and Women's Hospital
Rong Zhong, Brigham and Women's Hospital
Mai Chan Lau, Brigham and Women's Hospital
Kosuke Mima, Brigham and Women's Hospital
Keisuke Kosumi, Brigham and Women's Hospital
Teppei Morikawa, Brigham and Women's Hospital
Eric B. Rimm, Harvard T.H. Chan School of Public Health
Wendy S. Garrett, Broad Institute
Jacques Izard, University of Nebraska - LincolnFollow
Yin Cao, Washington University School of Medicine in St. Louis
Mingyang Song, Massachusetts General Hospital
Curtis Huttenhower, Harvard T.H. Chan School of Public Health
Shuji Ogino, Brigham and Women's Hospital
Andrew T. Chan, Massachusetts General HospitalFollow

Date of this Version

8-1-2021

Citation

Clinical and Translational Gastroenterology 2021;12:e00338.

doi:10.14309/ctg.0000000000000338

Comments

© 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology. Used by permission.

Abstract

INTRODUCTION: We recently described the sulfur microbial diet, a pattern of intake associated with increased gut sulfur-metabolizing bacteria and incidence of distal colorectal cancer (CRC). We assessed whether this risk differed by CRC molecular subtypes or presence of intratumoral microbes involved in CRC pathogenesis (Fusobacterium nucleatum and Bifidobacterium spp.).

METHODS: We performed Cox proportional hazards modeling to examine the association between the sulfur microbial diet and incidence of overall and distal CRC by molecular and microbial subtype in the Health Professionals Follow-Up Study (1986-2012).

RESULTS: We documented 1,264 incident CRC cases among 48,246 men, approximately 40% of whom had available tissue data. After accounting for multiple hypothesis testing, the relationship between the sulfur microbial diet and CRC incidence did not differ by subtype. However, there was a suggestion of an association by prostaglandin synthase 2 (PTGS2) status with a multivariable adjusted hazard ratio for highest vs lowest tertile of sulfur microbial diet scores of 1.31 (95% confidence interval: 0.99-1.74, Ptrend = 0.07, Pheterogeneity = 0.04) for PTGS2-high CRC. The association of the sulfur microbial diet with distal CRC seemed to differ by the presence of intratumoral Bifidobacterium spp. with an adjusted hazard ratio for highest vs lowest tertile of sulfur microbial diet scores of 1.65 (95% confidence interval: 1.14-2.39, Ptrend = 0.01, Pheterogeneity = 0.03) for Bifidobacterium-negative distal CRC. We observed no apparent heterogeneity by other tested molecular markers.

DISCUSSION: Greater long-term adherence to the sulfur microbial diet could be associated with PTGS2-high and Bifidobacterium-negative distal CRC in men. Additional studies are needed to further characterize the role of gut microbial sulfur metabolism and CRC.