August 26, 2019
By Will Boggs MD
NEW YORK (Reuters Health) - Oral antibiotic use appears to increase the risk of colon cancer and reduce the risk of rectal cancer, according to a database study.
"Our findings highlight that careful and appropriate use of antibiotics is very important, not only for avoidance of inducing antimicrobial, which is a major problem in treating patients currently, but also because of the potential impact on longer-term health and the development of chronic diseases," Dr. Cynthia L. Sears from Johns Hopkins University School of Medicine, in Baltimore, Maryland, told Reuters Health by email.
Previous epidemiological studies have suggested an association between antibiotic use and an increased risk of prostate, breast, lung and colon cancers, but findings have been inconsistent.
Dr. Sears and colleagues used data from the Clinical Practice Research Datalink in the U.K., the world's largest primary-care database, to investigate the associations between antibiotic use and site-specific colorectal-cancer risk.
Individuals who developed colon cancers were slightly, but significantly, more likely to be exposed to antibiotics (71.3% vs. 69.1%), whereas those with and without rectal cancers had comparable exposure to antibiotics (67.1% vs. 67.2%).
In the colon, the excess risk of cancer was duration-dependent and was more marked in the proximal colon. In the rectum, antibiotic use exceeding 60 days was associated with a 15% reduction in the odds of developing cancer, compared with no use (P=0.003).
Use of antibiotics with anti-anaerobic action were associated with an increased colon-cancer risk, while an inverse association with antibiotic exposure was seen for rectal cancer, regardless of effects on anaerobes, the researchers report in Gut, online August 19.
Among specific antibiotic classes, penicillins were associated with a 9% increase in the risk of colon cancer, whereas tetracyclines were associated with a 10% reduction in the risk of rectal cancer by 10%.
For colon cancers, the increased risk emerged after minimal antibiotic use and reached a plateau after 60 days of cumulative exposure. In contrast, the reduced risk of rectal cancer associated with antibiotic exposure was not seen until after 30 days of cumulative exposure and reached a plateau after 90 days.
Among participants with at least 15 years of follow-up, antibiotic use more than 10 years before the cancer diagnosis was associated with an increased colon-cancer risk, whereas earlier antibiotic use was not associated with colon-cancer risk. In contrast, the time window of antibiotic use was not significantly associated with the reduced rectal cancer risk.
"We hope that this reinforces to physicians and patients/the public that when antibiotics are needed they can be life-saving, but inappropriate use of antibiotics, such as for viral upper respiratory tract infections, is to be avoided," Dr. Sears said. "Similarly, we should all seek to take antibiotics targeted to any particular infection for the shortest time possible that is defined as effective for the infection."
She added, "This work was eye-opening to us, and while this work does not define causality, it broadens and emphasizes our understanding of the importance of antibiotic stewardship and good practices in use of antibiotics."
Dr. Yu-Xiao Yang from Perelman School of Medicine at the University of Pennsylvania, in Philadelphia, who has also researched the impact of antibiotic exposure on the risk of colorectal cancer, told Reuters Health by email, "The clinical implication is that antibiotic-induced alterations in gut microbiome might play an important role in the pathogenesis of colorectal cancer, perhaps more so for proximal colon cancer. There may be one more reason now to exercise judicious prescribing of antibiotics."
"These results are hypothesis generating," said Dr. Yang, who was not involved in the study. "More research is needed."
Dr. Andrew T. Chan from Massachusetts General Hospital and Harvard Medical School, in Boston, who also was not involved in the new work, recently found an increased risk of colorectal adenoma with long-term antibiotic use in early-to-middle adulthood. He told Reuters Health by email, "These studies highlight the important role that the bacteria that reside in our intestines may play in the development of colorectal cancer. Frequent use of antibiotics may alter the naturally occurring composition of the bacteria in our bodies which could lead to health consequences, including predisposing the colon to the development of cancer."
"These data support the importance of physicians being judicious about their use of antibiotics," he said. "Antibiotics are often too easily prescribed because they are usually well tolerated in the short-term with few side effects. However, emerging data suggest that the frequent use of antibiotics might alter our bodies' natural balance of bacteria, leading to long-term health effects."
"These data support the need for further research into how our complex intestinal microbial communities influence the development of cancer and how they can be potentially manipulated to actually prevent cancer," Dr. Chan said.
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