In an extensive “data mining” analysis of British medical records, researchers at the Johns Hopkins Kimmel Cancer Center conclude 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 in the August 20 issue of the journal Gut, highlight the need for judicious use of this broad category of drugs, which are frequently improperly or overprescribed, the report authors say.
Study leader Cynthia L. Sears, MD, Bloomberg~Kimmel Professor of Cancer Immunotherapy at the Johns Hopkins Kimmel Cancer Center cautions that medical records studies like hers are not designed to demonstrate cause and effect, but to identify possible associations between risk factors and disease. But she notes that because the database 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 radical change that antibiotics wreak on the microbiome.
To learn more about the association between antibiotics and colorectal cancers, Sears, Zhang, and their colleagues mined data from the Clinical Practice Research Datalink (CPRD), one of the world’s largest electronic medical record databases of “anonymized” clinical records, information that does not identify individual patients. CPRD holds information on more than 11 million patients in the U.K., 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.
The researchers found that those 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 percent compared to 69.1 percent). Those with rectal cancers did not show that association and 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 percent for cancer in the proximal colon (the first and middle parts of the colon) but not the distal colon (last part of the 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 15–30 days of total antibiotic exposure (approximately eight percent increased risk with 15–30 days of total antibiotic exposure and approximately 15 percent 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.
Johns Hopkins Medicine has the full article