Long-term Antibiotic Use in Early to Midlife Linked to Colorectal Adenomas Later

Jennifer Garcia

April 05, 2017

Antibiotic exposure in early to midlife may increase the risk for colorectal adenoma, the precursor for the majority of colorectal cancers, after age 60 years, a new study has found. These findings were published online April 4 in Gut.

"These data provide additional support for the association of antibiotics with colorectal cancer and the potential mediating role of the gut microbiome in carcinogenesis," Andrew T. Chan, MD, MPH, from Massachusetts General Hospital, Harvard Medical School, and Harvard T. H. Chan School of Public Health, Boston, Massachusetts, and colleagues write.

Using information from the Nurses' Health Study, the researchers evaluated data regarding antibiotic use and subsequent disease outcomes from 16,642 women who were aged 60 years or older in 2004. Their analysis included only women who reported their antibiotic use through age 59 years and who had undergone at least one colonoscopy between 2004 and 2010. Participants in the Nurses' Health Study answered questionnaires every 2 to 4 years to collect data on demographics, lifestyle, nutrition, and medical history.

The researchers identified 1195 cases of adenomas and found that compared with nonusers, women who used antibiotics for 2 months or longer between ages 20 and 39 years were 36% more likely to develop colorectal adenoma (multivariable odds ratio [OR] for adenoma, 1.36; 95% confidence interval [CI], 1.03 - 1.79). Further, women who used antibiotics for 2 months or longer between 40 and 59 years of age were 69% more likely to develop colorectal adenoma (multivariable OR for adenoma, 1.69; 95% CI, 1.24 - 2.31). In both groups, the associations were similar for low-risk vs high-risk adenomas, but were stronger for adenomas located in the proximal colon.

Similarly, women aged 20 to 39 years and 40 to 59 years who used antibiotics for longer than 15 days were 73% more likely to develop colorectal adenoma compared with nonusers (multivariable OR for adenoma, 1.73; 95% CI, 1.19 - 2.51). Interestingly, recent exposure to antibiotics (within 4 years of their colonoscopy) was not associated with an increased risk for colorectal adenoma.

Citing previous studies that have also found a similar association, Dr. Chan and colleagues write: "Our study significantly extends the findings of these prior studies by demonstrating an association of antibiotics with colorectal adenoma and its location, providing additional support that the association of antibiotics with colorectal cancer may be causal."

The researchers acknowledge the limitations of their study such as the lack of information on the effects of specific antimicrobial classes, as well as the possibility for residual confounding because of the observational study design. Further, they note that research to confirm these findings in men and other racial or ethnic groups will be needed.

The authors recognize that the role an altered gut microbiome may play in the development of colorectal neoplasia is still unclear, but note that "[t]he findings, if confirmed by other studies, suggest the potential need to limit the use of antibiotics and sources of inflammation that may drive tumour formation."

Funding for this study was provided by the National Institutes of Health, the Raymond P. Lavietes Foundation, the Project P Fund, the Friends of the Dana-Farber Cancer Institute, the Bennett Family Fund, and the Entertainment Industry Foundation through the National Colorectal Cancer Research Alliance. Dr Chan previously served as a consultant for Bayer Healthcare, Pozen, and Pfizer for work unrelated to this study.

Gut. Published online April 4, 2017. Full text

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