- Exposure to antibiotics in early to middle adulthood (ages 20–39 and 40–59) was significantly associated with increased risk of colorectal adenoma after age 60
- Antibiotic use within four years was not associated with an increased risk
- These data provide support for an association of antibiotic use with colorectal cancer and the potential mediating role of the gut microbiome
Increasing evidence suggests that gut microbiota hold a role in colorectal carcinogenesis, and that use of antibiotics may initiate or promote colorectal neoplasia.
Recent studies using cancer registries and health care claims in Europe suggest an association between antibiotic exposure and colorectal cancer. However, those studies had substantial limitations, such as short follow-up time, results being affected by close medical surveillance or retrospective studies that provide little information about why antibiotics were used.
Researchers at Massachusetts General Hospital participate in the Nurses' Health Study (NHS) run by Harvard University, a very large, ongoing study of U.S. female nurses that started in 1976. Upon enrollment into the study, participants' ages ranged from 30-55. In an analysis nested within that study, Andrew T. Chan, MD, MPH, instructor in the Department of Medicine, chief of Clinical and Translational Epidemiology and physician in the Mass General Cancer Center and physician at the Mass General Cancer Center, and colleagues found additional support for the association of antibiotics with colorectal cancer. The findings are published in Gut.
Since 2004, participants in the NHS have been questioned about antibiotic use, lifestyle risk factors for colorectal cancer and endoscopic screening. Since 2010, participants have reported cases of adenoma, and the researchers followed up by obtaining informed consent to acquire medical records and pathology reports.
The study analyzed 16,642 women age ≥60 who reported their history of antibiotic use through age 59 via the 2004 questionnaire and had undergone at least one colonoscopy between 2004 and 2010.
Among these women, the researchers documented 1,195 newly diagnosed adenomas. Compared with non-users, women who used antibiotics for ≥ two months when they were 20 to 39 years old had a multivariable odds ratio (OR) for adenoma of 1.36 (95% CI, 1.03–1.79) (P for trend = .002).
The associations were similar for high-risk versus low-risk adenomas, but longer duration of antibiotic treatment was more strongly associated with adenomas in the proximal colon than in the distal colon.
Likewise, women who used antibiotics for ≥ two months when they were 40 to 59 years old had a multivariable OR for adenoma of 1.69 (95% CI, 1.24–2.31) (P for trend = .001). The associations were again similar for high-risk versus low-risk adenomas, and a stronger association was observed for proximal adenomas.
Compared with women who did not use antibiotics between ages 20 and 39 or between ages 40 and 59, women who used antibiotics for >15 days during both periods had a multivariable OR for adenoma of 1.73 (95% CI, 1.19–2.51).
Recent antibiotic use did not appear to be associated with risk of colorectal adenoma. Specifically, among women who had a colonoscopy between 2008 and 2010, antibiotic use in the past four years was not associated with risk of adenoma.
A potential link between antibiotic use and development of colorectal neoplasia is biologically plausible, the researchers comment. Exposure to antibiotics shifts the gut microbiota to a state of dysbiosis generally marked by loss of diversity, shifts in metabolic capacity and reduced resistance to invading pathogens. Interactions of dysbiotic microbiota with mucosal cells may be involved in the initiation and/or promotion of colorectal carcinogenesis.
Furthermore, the pathogens that require treatment with antibiotics may induce inflammation, a known risk for colorectal cancer.
Additional research is needed to understand how antibiotic exposure affects gut microbial composition and function, particularly with regard to mechanisms that underlie colorectal carcinogenesis.
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