Johns Hopkins Researchers Find Link Between Antibiotics and Colon Cancer

Researchers from Johns Hopkins Kimmel Cancer Center recently found that antibiotic use may influence the development of colon cancer years later. This analysis of British medical records revealed that even a single antibiotic treatment course may be enough to instill these associated cancer risks. This work suggests that physicians should minimize the prescription of antibiotics, which the authors note are often overprescribed. This work was published on August 20 in the journal Gut.

“The primary message of this study is the importance of antibiotic stewardship: not treating common viral infections with antibiotics, using them for the shortest time period possible, and using targeted antibiotics rather than broad spectrum ones,” explained study leader Cynthia L. Sears, M.D., Bloomberg~Kimmel Professor of Cancer Immunotherapy at the Johns Hopkins Kimmel Cancer Center. “This research adds to our understanding that these drugs can have significant off-target effects, including the induction of chronic illnesses.”

Sears noted that this study of medical records does not show a causal relationship between antibiotics and cancer, but that it identifies antibiotic use as a potential risk factor that is correlated to increased colon cancer rates. Because the database evaluated contained such a large body of information, however, the authors concluded that this observed clinically meaningful. They propose that this increase in colon cancer risk is brought about by the significant changes that antibiotics create in the microbiome, or portfolio of bacteria that reside in the gut.

There is a growing body of epidemiological database studies and other research linking antibiotic use to colorectal cancer risks, according to Sears and Jiajia Zhang, M.D., M.P.H., a Bloomberg~Kimmel Institute for Cancer Immunotherapy researcher. There are several shortcomings of these previous works, however, with several of them failing to control for other cancer risks such as smoking, alcohol use, diabetes, and others. Sears and Zhang also feel these previous works present bias in patient reports of antibiotic use, lack data differentiating colon and rectal cancers, and did not use large enough sample sizes.

Background of the Johns Hopkins Study

In their work, Sears and colleagues analyzed data from the Clinical Practice Research Datalink (CPRD), one of the largest anonymized medical record databases available. This resource contains data regarding over 11 million patients in the U.K. such as drug prescriptions and diagnosis. This was the first population-based study that aimed to examine the correlation between antibiotic exposure and colorectal cancer risks.

The researchers analyzed data from 1989 to 2012, identifying 28,890 cases of colorectal cancer in this 23-year window. Each of these cases was matched with up to five healthy controls who were similar in age, gender, and care provider, but had no history of colorectal cancer. A total of 137,077 control cases were used in this work.

In addition to antibiotic use, risk factors assessed for correlation to colorectal cancer included obesity, alcohol use, diabetes, and smoking. The team unsurprisingly found that many of these known risk factors were linked to higher rates of colorectal cancer but found that antibiotic exposure still presented a risk after accounting for these other factors as well. They noted that those who had colon cancer were slightly more likely to have had prior antibiotic exposure than their healthy counterparts after accounting for these factors (71.3% vs. 69.1%). This association was not present in those with rectal cancers. Antibiotic use was associated with an increased risk of roughly 15% for cancer in the proximal colon but not in the distal colon. Furthermore, this risk occurred most strongly after exposure to antibiotics that target anaerobic bacteria, such as penicillin. The colon cancer cases were linked to antibiotic exposure at least 10 years prior.

The researchers noted that the onset of colon cancer risk was very rapid, with an 8% increased risk presenting only 15-30 days after exposure to antibiotics. At 30 days or longer after this exposure, this increased risk rose to 15%. This association was inverse for patients with rectal cancer, with antibiotic exposure being negatively correlated to cancer in this region.

Sears noted that although antibiotics are effective in killing bacterial infections, they can kill beneficial bacteria in the gut and allow pathogenic ones to survive. These surviving bacterial strains could display carcinogenic qualities, encouraging the growth of malignancies in the colon.