In an extensive data mining analysis of British medical records, researchers found that taking even a single course of antibiotics might boost—albeit slightly—the risk of developing colon cancer, but not rectal cancer, a decade later. The findings, reported by Zhang et al in Gut, highlight the need for judicious use of this broad category of drugs, which are frequently improperly or overprescribed, according to the study authors.
“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,” said lead study author Cynthia L. Sears, MD. “This research adds to our understanding that these drugs can have significant off-target effects, including the induction of chronic illnesses.”
Antibiotics are widely prescribed throughout the world to treat bacterial infections, and there is growing evidence, including several epidemiologic database studies, that link use of these drugs to the risk of colorectal cancer, said researchers. However, these past studies have had a variety of drawbacks, including failure to control for other colorectal cancer risk factors (family history, history of obesity, smoking, alcohol use, and diabetes) recall bias in patients’ recollections about antibiotic use, failure to separate data about colon and rectal cancers, and too few study participants to produce meaningful conclusions.
To learn more about the association between antibiotics and colorectal cancers, researchers mined data from the Clinical Practice Research Datalink (CPRD), one of the world’s largest electronic medical record databases of anonymized clinical records. CPRD holds information on more than 11 million patients in the United Kingdom, including data on drug prescribing and diagnoses, making this study the first population-based study to examine the association of antibiotic exposure and risk of colorectal cancer.
Focusing on a 23-year period from January 1, 1989, to December 31, 2012, the researchers found 28,890 cases of colorectal cancer. They matched each of these patient records with up to five healthy controls who never developed this disease, but who had similar characteristics, including age, gender, and where their general practitioner practiced, for a total of 137,077 control cases for comparison.
They then used the medical records to identify and evaluate each case history for colorectal cancer risk factors, such as a history of obesity, smoking, alcohol use, and diabetes, as well as antibiotic use.
Researchers found that patients who developed colorectal cancer were more likely to have one or more of the known risk factors. However, when they accounted for these factors in their statistical evaluation, they found that those who developed colon cancer were slightly more likely to have been exposed to antibiotics (71.3% vs 69.1%). Those with rectal cancers did not show that association—they had about the same antibiotic exposure compared to healthy subjects.
Further investigation showed that antibiotic exposure was only associated with increased risk of approximately 15% for cancer in the proximal colon but not the distal colon and this risk happened particularly after exposure to classes of antibiotics that kill anaerobic bacteria, such as those in the penicillin family.
Among the compelling findings, the researchers say, was the rapid onset of increased colon cancer risk, beginning with only 15 to 30 days of total antibiotic exposure (approximately 8% increased risk with 15 to 30 days of total antibiotic exposure and approximately 15% increased risk with 30 or more days of total antibiotic exposure). However, the association was reversed for rectal cancer: the more total antibiotic exposure—specifically, total exposures of 60 days or more—the less likely they were to have cancer in this location. Cancers that developed in the colon were linked with antibiotic exposure at least 10 years earlier. There was no increased risk with exposures less than 10 years prior.
The Gut Microbiome
In a statement, Dr. Sears cautioned that medical records studies like hers are not designed to demonstrate cause and effect, but to identify possible associations between risk factors and disease. She noted that because the database used for analysis held so much specific information over a long period of time that the study authors concluded that the most likely explanation for the bump in colon cancer risk is the change that antibiotics have on the microbiome.
Although antibiotics are most often highly effective at eradicating bacterial infections, Dr. Sears explained, they also can change the balance of the gut biome by killing beneficial bacteria and allowing pathogenic ones to thrive. Some of these surviving bacteria could be carcinogenic, encouraging polyps to grow and develop into malignant tumors.
The authors concluded, “Oral antibiotic use is associated with an increased risk of colon cancer but a reduced risk of rectal cancer. This effect heterogeneity may suggest differences in gut microbiota and carcinogenesis mechanisms along the lower intestinal tract.”
Disclosure: This study was supported by the Fisher Center for Environmental Infectious Diseases. For full disclosures of the study authors, visit gut.bmj.com.
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