Exposure to oral antibiotics was shown to be associated with a risk for colorectal cancer (CRC), but this risk was varied based on anatomical location in the colon, according to a study published in the journal Gut.

Microbiome dysbiosis predisposes to CRC, yet the association between oral antibiotic exposure and risk patterns from a population-based study is still lacking. Therefore, the aim of this matched, case-controlled study was to examine the association between the use of oral antibiotics and the risk for CRC at specific locations in the colon by reviewing data from the world’s largest primary care database, the Clinical Practice Research Datalink, from 1989-2012. Case patients were defined as patients who were diagnosed with CRC and control patients were defined as patients who were not diagnosed with CRC over the course of the study time frame.

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There were up to 5 controls for each case patient, matched for age, gender, practitioner site, and year of registration in the database. Specific locations of interest in the colon included the proximal colon (cecum, ascending colon, hepatic flexure, and transverse colon), distal colon (splenic flexure, descending colon, and sigmoid colon), or rectal area (rectum and rectosigmoid junction). Antibiotic exposure was defined as the number of days that an antibiotic was administered, and antibiotics were categorized based on class and effect.

The researchers identified 28,980 CRC case patients and 137,077 matched control patients in the database. The CRC case patients were more frequently overweight or obese, to have smoked, to have moderate to heavy alcohol consumption, to have diabetes, to have had a colonoscopy, and less likely to have chronically used nonsteroidal anti-inflammatory drugs than the control patients. Patients diagnosed with colon cancer were more frequently women, overweight or obese, to have smoked, to use alcohol, to have diabetes, and to have had a colonoscopy than patients diagnosed with rectal cancer.

Oral antibiotics were prescribed to 70% of the CRC case patients and 68.5% of the control patients (P <.001). When compared with the control patients, CRC case patients with colon cancer were more likely to have been exposed to antibiotics (P <.001), while case patients with rectal cancer had similar exposure to antibiotics (P =.96). When compared with the control patients, CRC case patients with colon cancer were more likely exposed to both anti-anaerobic antibiotics and anti-aerobic antibiotics, while case patients with rectal cancer were less likely exposed to anti-aerobic antibiotics. Case patients with colon cancer were more frequently exposed to cephalosporins and quinolones, and case patients with rectal cancer were less frequently exposed to tetracyclines and macrolides.

The risk for colon cancer was increased in a dose-dependent fashion (P <.001), with the risk higher in the proximal colon (P =.046) than the distal colon (P =.400). The risk for rectal cancer was inversed, with a risk reduction of 15% after an exposure to antibiotics lasting at least 60 days, as compared with no use (adjusted odds ratio [OR]= 0.85, 95% CI 0.79 – 0.93, P =.003). Anti-anaerobic antibiotics increased the risk for colon cancer (P <.001), but inversely affected rectal cancer (P =.054). Penicillin exposure was associated with an increased risk for colon cancer (adjusted odds ratio [OR] =1.09, 95% CI 1.05 – 1.13) in a dose-dependent fashion (P <.001) but was not associated with a risk for rectal cancer (P =.92). Tetracycline exposure decreased the risk for rectal cancer (adjusted OR= 0.90, 95% CI 0.84 – 0.97).

Minimal antibiotic exposure was associated with an increased risk for proximal colon cancer but not distal colon cancer, and antibiotic exposure decreased the risk for rectal cancer after 30 days of cumulative exposure. There was a significant interaction between antibiotic exposure and cancer location, colon or rectal (P <.001), and location in the colon, proximal or distal (P =.019).

Limitations of this study include a lack of lifestyle factors in the database, uncertainty about prescription filled and treatment adherence, the inability to assess the effect that age and antibiotic exposure had on cancer risk, and the possibility of incorrect classification in the database.

The researchers concluded, “that use of oral antibiotics was associated with CRC risk, but the effect size and pattern of risk varied by anatomical location in the colorectum.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Zhang J, Haines C, Watson AJM, et al. Oral antibiotic use and risk of colorectal cancer in the United Kingdom, 1989-2012: a matched case-control study [published online August 19, 2019]. Gut. doi: 10.1136/gutjnl-2019-318593

This article originally appeared on Gastroenterology Advisor