Objective Recent evidence suggests that antibiotic use, which alters the gut microbiome, is associated with an increased risk of colorectal cancer. However, the association between antibiotic use and risk of colorectal adenoma, the precursor for the majority of colorectal cancers, has not been investigated.
Design We prospectively evaluated the association between antibiotic use at age 20–39 and 40–59 (assessed in 2004) and recent antibiotic use (assessed in 2008) with risk of subsequent colorectal adenoma among 16 642 women aged ≥60 enrolled in the Nurses' Health Study who underwent at least one colonoscopy through 2010. We used multivariate logistic regression to calculate ORs and 95% CIs.
Results We documented 1195 cases of adenoma. Increasing duration of antibiotic use at age 20–39 (ptrend=0.002) and 40–59 (ptrend=0.001) was significantly associated with an increased risk of colorectal adenoma. Compared with non-users, women who used antibiotics for ≥2 months between age 20 and 39 had a multivariable OR of 1.36 (95% CI 1.03 to 1.79). Women who used ≥2 months of antibiotics between age 40 and 59 had a multivariable OR of 1.69 (95% CI 1.24 to 2.31). The associations were similar for low-risk versus high-risk adenomas (size ≥1 cm, or with tubulovillous/villous histology, or ≥3 detected lesions), but appeared modestly stronger for proximal compared with distal adenomas. In contrast, recent antibiotic use within the past four years was not associated with risk of adenoma (ptrend=0.44).
Conclusions Long-term antibiotic use in early-to-middle adulthood was associated with increased risk of colorectal adenoma.
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Contributors SO, ELG and ATC contributed equally to the article. YC and ATC had full access to all of the data in the study, and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: YC, ELG and ATC. Acquisition of data: YC, KW, CSF, ELG and ATC. Analysis and interpretation of data: all co-authors. Drafting of the manuscript: YC and ATC. Critical revision of the manuscript for important intellectual content: all co-authors. Statistical analysis: YC. Obtained funding: YC, KW, CSF, JI, WSG, CH, SO, ELG and ATC. Administrative, technical or material support; and study supervision: ATC
Funding This work was supported by US National Institutes of Health (NIH) grants (P01 CA87969 to MJS; UM1 CA186107 to MJS; P50 CA127003 to CSF; R01 CA202704 to JI, WSG, CH and ATC; R01 CA137178 to ATC; K24 DK098311 to ATC; R01 CA151993 to SO; R35 CA197735 to SO); and by grants from The Raymond P. Lavietes Foundation (to YC), The Project P Fund, The Friends of the Dana-Farber Cancer Institute, The Bennett Family Fund and The Entertainment Industry Foundation through National Colorectal Cancer Research Alliance.
Competing interests ATC previously served as a consultant for Bayer Healthcare, Pozen and Pfizer for work unrelated to the topic of this manuscript. This study was not funded by Bayer Healthcare, Pozen or Pfizer.
Ethics approval This study was approved by the institutional review board at the Brigham and Women's Hospital.
Provenance and peer review Not commissioned; externally peer reviewed.
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