Use of antibiotics and increased risk of colon cancer?

Even a single course of antibiotics has been shown to be associated with an increased risk of developing colon cancer nearly ten years later, as suggested by the results of a matched case-control study. .

The study revealed that this risk was particularly apparent for proximal colon cancers and the use of anti-anaerobic antibiotics.

According to the authors, this finding that oral exposure to anti-anaerobic antibiotics would have had the most significant effect on the risk of colon cancer is intriguing, as these agents "significantly disrupt" the microbiome intestinal, composed mainly of anaerobes.

"It is [therefore] possible that the disturbed microbiota allows the acquisition or development of a carcinogenic microbiota of the colon ", suggest the authors.

"Whether antibiotic exposure is causal or contributing to the risk of colon cancer, our findings underscore the importance of judicious use of antibiotics by clinicians," they conclude.

"The main message of this study is the importance of antibiotic management: do not treat common viral infections with the help of antibiotics, use them for as short a time as possible, and use targeted antibiotics rather than broad-spectrum antibiotics, "wrote Cynthia Sears, MD, a professor of cancer immunotherapy at the Johns Hopkins Kimmel Cancer Center in Baltimore, Maryland, said in a statement.

The study was published online yesterday in the journal Intestine.

For the study, Sears and colleagues analyzed data from the Clinical Practice Research Datalink (CPRD) database in the UK, the largest primary care database in the world, according to the authors.

The team identified 28,980 cases of colorectal cancer (CRC) over a 23-year period (1989-2012) and compared them to 137,077 controls. They then examined various risk factors for CRC, including the use of oral antibiotics, and compared them between the patient group and the control group.

The researchers noted that patients with CRC were more likely than control group members to be overweight (35.2% vs. 33.8%) and obese (18.6% vs. 16.0%). 4%), having already smoked (49.9% vs. 46.9%), having moderate to high alcohol consumption (13.8% vs. 11.4%), a history of diabetes (8%); 8% vs. 7.7%) and colonoscopy (3.5% vs. 2.9%); The researchers found that patients with CRC were less likely than control groups to have chronic nonsteroidal anti-inflammatory drugs (NSAIDs) (7.2% vs. 9%).

They also found that after a median follow-up of 8.1 years, participants who developed colon cancer were significantly more likely to have taken an antibiotic (at 71.3% compared to controls at 69.1%). % (P <0.001).

In contrast, there was little difference in antibiotic exposure between participants who developed rectal cancer and those who did not; in this case, the exposure to antibiotics was the same in both groups, to 67.1% in the rectal cancer group and to 67.2% in the control group.

"Among patients whose location of CRC was known, participants with proximal colon cancer were more likely to be exposed to antibiotics, particularly those with anti-anaerobic effects, then that participants with distal colon cancer had similar exposure to controls in controls, regardless of the spectrum of antibiotics, "said the authors. observe.

However, the magnitude of the effect of antibiotic exposure on the risk of CRC as well as the mode of use differed depending on the location of the tumor.

In the colon, "an excessive risk has been observed with the increased use of antibiotics depending on the dose, with no use as a reference," note the researchers.

For example, after adjusting for known risk factors for CRC, including smoking and alcohol consumption, the effect of antibiotic use on proximal colon cancer was increasingly important with prolonged use of antibiotics from about 8% to 15 to 30 days of total antibiotic exposure. at 15% with 30 days and more total exposure to antibiotics.

Again, however, the same observation was not made for distal colon cancer, where no link was observed between the duration of antibiotic exposure and the risk of CRC.

And in the rectum, participants who used antibiotics for more than 60 days were 15% less likely to develop rectal cancer during the study period than participants who did not take it , with an odds ratio of 0.85, the researchers pointed out.

"For colon cancers, antibiotic exposure was associated with a significantly increased risk, with an increased effect after minimal use of antibiotics and a plateau after 60 days of cumulative exposure," write Researchers.

This was true for proximal colon cancers, but again, not for distal colon cancers, they add.

For rectal cancer, "there was a reduction in cancer risk associated with cumulative exposure to an antibiotic", they point out, an effect that was observed only after 30 days cumulative exposure to antibiotics and which reached a plateau after 90 days of exposure.

Class of antibiotics

Nearly 60% of cohort study participants were prescribed more than one class of antibiotics.

However, antibiotics with anti-anaerobic properties were associated with a significantly higher risk of colon cancer, particularly colon cancer in the proximal colon (P <0.001).

This was not yet the case of rectal cancer, where all classes of antibiotics seemed to have a protective effect against its development, regardless of their effects on the intestine and anaerobes.

The researchers point out that exposure to tetracyclines seems to have a particularly protective effect on rectal cancer.

Among the different classes of antibiotics, "the use of penicillins was associated with an increased risk of colon cancer … especially in the proximal colon, but not cephalosporins, quinolones, macrolides or sulfa. / trimethoprim, "the authors observed.

Penicillins also affected the risk of colon cancer in a dose-dependent manner (although the risk of rectal cancer is not the same).

The authors suggest that penicillins also do not affect the risk of distal colon cancer, an "intriguing" result, as the proximal colon is the first site exposed to antibiotics that are not absorbed in the intestine. hail and before modification or degradation of the drug in the colon. .

In their discussion, the authors indicate that previous studies have suggested a link between the use of antibiotics and colorectal cancer, but note that it is "the greatest analysis of # 39; antibiotic-CRC association to date ".

The study was funded by the Johns Hopkins Fisher Center Discovery Program and the Bloomberg-Kimmel Institute for Cancer Immunotherapy. Sears has not revealed any relevant financial relationship. Several co-sponsors disclosed relevant financial interests; this information is listed in the article of origin.

Intestine. Posted online 20 August 2019. Full text

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