Association between Broad-Spectrum Antibiotic Use and Risk of Early-Onset Colorectal Cancer

Exposure to broad-spectrum antibiotics may alter the risk of early-onset colorectal cancer (eoCRC) via gut dysbiosis. We evaluated the associations between oral broad-spectrum and narrow-spectrum antibiotic use and eoCRC.

We conducted a nested case-control study within Kaiser Permanente Southern California (KPSC). Cases were persons aged 15 to 49 years with in situ or invasive colorectal adenocarcinoma (2009-2021); controls were individually matched 10:1 on age, sex, and length of KPSC membership. Those with ≥15 years of membership were included to assess exposure 2 to 15 years earlier. Data were collected from electronic health records. Crude and multivariable conditional logistic regression was used to evaluate antibiotic use from 10 to 14.9, 5 to 9.9, and 2 to 4.9 years before diagnosis/index date with the risk of overall colorectal cancer, colon cancer, and rectal cancer.

A total of 295 cases and 2,794 controls were included. In the 10 to 14.9 years before diagnosis/index date, the use of broad-spectrum antibiotics was not associated with eoCRC [adjusted odds ratio (aOR) for any use = 1.07 (95% confidence interval, 0.82-1.40); aOR for >90 days of cumulative use = 1.40 (0.82-2.38)]. An elevated risk of colon adenocarcinoma was suggested for >90 days of cumulative use of broad-spectrum antibiotics [aOR = 2.04 (1.09-3.85)]. No clear association was observed for broad-spectrum antibiotic use within 5 to 9.9 or 2 to 4.9 years prior to diagnosis or with rectal cancer during any period or for narrow-spectrum antibiotics in any exposure window.

An association between long-term cumulative use of broad-spectrum antibiotics and early-onset colon cancer is suggested.

Further investigation into antibiotics and eoCRC risk by the duration of use and the window of exposure is warranted.