Broad-spectrum antibiotic use and risk of early-onset colorectal cancer.

person Chun Chao Kaiser Permanente Southern California, Pasadena, CA info_outline Chun Chao, Lanfang Xu, Jessica Chubak, Jane C. Figueiredo, Darios Getahun, Kimberly L. Cannavale, Alec Gilfillan, Bechien U Wu

Authors person Chun Chao Kaiser Permanente Southern California, Pasadena, CA info_outline Chun Chao, Lanfang Xu, Jessica Chubak, Jane C. Figueiredo, Darios Getahun, Kimberly L. Cannavale, Alec Gilfillan, Bechien U Wu Organizations Kaiser Permanente Southern California, Pasadena, CA, MedHealth, Inc, Houston, TX, Kaiser Permanente, Seattle, WA, Cedars-Sinai Cancer Institute, Los Angeles, CA, Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA Abstract Disclosures Research Funding National Cancer Institute/U.S. National Institutes of Health Background: The incidence of early-onset colorectal cancer (eoCRC) diagnosed under age 50 is rising in the United States, but the underlying causes are largely unknown. Use of broad-spectrum antibiotics can induce intense gut dysbiosis, which is strongly implicated in CRC carcinogenesis. Emerging evidence supports a link between broad-spectrum antibiotic use and CRC. We evaluated the associations between oral broad-spectrum antibiotic use and risk of eoCRC. Methods: We conducted a nested case-control study within Kaiser Permanente Southern California (KPSC). Cases were persons aged 15-49 years with invasive colorectal adenocarcinoma diagnosis between 2009-2021; controls were matched at 10:1 ratio on age, sex at birth, and length of KPSC membership. Those with less than 15 years of prior membership at diagnosis date or controls’ index date were excluded to allow evaluation of exposure up to 15 years prior. We extracted all study data, including use of antibiotics by drug type and days of prescriptions, from KSPC’s electronic medical records. Conditional logistic regression was used to evaluate antibiotic use from three etiologic periods: 10-15, 5-10, and 2-5 years prior to diagnosis/index date, adjusting for potential confounders (narrow-spectrum antibiotics use, clinical and lifestyle risk factors, race/ethnicity, body mass index) with a crude p-value < 0.10. Analyses were conducted overall and separately for colon cancer. Results: A total of 310 cases (mean age at diagnosis 44.5 years, 52% female, 33% non-Hispanic White) and 2,976 controls were included. In the 10-15 years prior to diagnosis/index date, 65% of cases and 62% of controls used broad-spectrum antibiotics. Broad-spectrum antibiotic use was not associated with eoCRC overall [OR = 1.15 (95% CI: 0.88-1.49)]. An increased risk was suggested for > 3 months of cumulative use: OR = 1.07 (0.81-1.42) for ≤1 month; 1.26 (0.87-1.84) for 1-3 months; and 1.59 (0.95-2.65) for > 3 months. The association between exposure and colon adenocarcinoma was: OR = 1.26 (0.91-1.72) for any use; OR = 1.17 (0.83-1.64) for ≤1 month; and OR = 1.50 (0.99-2.27) for > 1 month. No association was observed between broad-spectrum antibiotic use within 5-9.9 years or 2-4.9 years prior to diagnosis and risk of eoCRC overall or for the colon site. Conclusions: Our findings suggest a possible association between cumulative longer-term use of broad-spectrum antibiotics and increased risk of eoCRC. The etiologic window for assessing antibiotic exposure appears to be relevant. Larger studies with long-term follow-up are needed to confirm these findings.