Antibiotics may be associated with colon cancer risk in dose-dependent fashion

A case-control study found that patients who developed colon cancer, particularly in the proximal colon, were more likely to have taken antibiotics, whereas antibiotic use was not associated with increased risk of rectal cancer.

Greater exposure to antibiotics, particularly those with anti-anaerobic activity, may be associated with an increased risk of colon cancer, but not rectal cancer, a study found.

Researchers conducted a matched case-control study of colorectal cancer cases and up to five matched controls using a British database of anonymized clinical records with population-based data collected prospectively from 1989 to 2012. Results were published by Gut on Aug 19. There were 28,980 cases of colorectal cancer and 137,077 control subjects. The median follow-up was 8.1 years (interquartile ratio, 4.9 to 12.3 years). Antibiotics had been prescribed to 20,278 (70%) patients with colorectal cancer and 93,862 (68.5%) controls (P<0.001). Participants who developed colon cancer were more likely to have used antibiotics compared to controls (71.3% vs. 69.1%; P<0.001). Those with rectal cancer had comparable exposure to antibiotics as controls (67.1% vs. 67.2%; P=0.96).

Antibiotic use was associated with increased risk of colon cancer in a dose-dependent fashion (P<0.001 for trend). Significant interactions were detected between antibiotic use and tumor location (colon vs. rectum, P<0.001 for interaction; proximal colon vs. distal colon, P=0.019 for interaction). The association between antibiotic use and cancer was seen for antibiotic use occurring more than 10 years before diagnosis (adjusted odds ratio [aOR], 1.17; 95% CI, 1.06 to 1.31).

There was an inverse association between antibiotic use and rectal cancer (P=0.003 for trend), particularly with antibiotic exposure of more than 60 days (aOR, 0.85; 95% CI, 0.79 to 0.93) compared to no antibiotic use. Penicillins, particularly ampicillin/amoxicillin, were associated with increased risk of colon cancer (aOR, 1.09; 95% CI, 1.05 to 1.13). Tetracycline use was associated with reduced risk of rectal cancer (aOR, 0.90; 95% CI, 0.84 to 0.97).

Limitations of the study include the fact that 10% to 20% of data for lifestyle factors were missing and that patients with immunodeficient conditions were excluded, the authors noted. “The findings present a pattern of antibiotic-[colorectal cancer] risk by tumour location and type of antibiotics, and increase the importance for physicians to use antibiotics judiciously,” they wrote. “This study will spur future studies of the microbes and mechanisms contributing to antibiotic–microbiome cancer risk, and development of approaches to intervene and mitigate the effects.”