In a Swedish study reported in JAMA Network Open, Cao et al found that females born via cesarean delivery were at an increased risk of early-onset colorectal cancer vs those born via vaginal delivery. No increased risk was observed among males born via cesarean delivery.
As noted by the investigators, documented short-term risks associated with birth via cesarean delivery include reduced intestinal gut microbiome diversity. Although data on long-term effects are limited, there is evidence that cesarean delivery may be associated with higher risks of immune-mediated chronic inflammatory diseases, obesity throughout life, and diabetes—all likely mediated by early-life gut dysbiosis persisting through adulthood.
Study Details
The population-based, nationwide, case-control study involved patients diagnosed with colorectal cancer between ages 18 and 49 years from 1991 to 2017. Up to five general population control individuals without colorectal cancer were matched with each colorectal cancer case for age, sex, calendar year, and county of residence.
Key Findings
A total of 564 cases of incident early-onset colorectal cancer were identified (mean age = 32.9 years); of these, 55 (9.8%) individuals had been born via cesarean delivery. The matched control cohort consisted of 2,180 individuals (mean age = 32.7 years) without colorectal cancer; of these, 175 (8.0%) were born via cesarean delivery.
On multivariate analysis adjusting for matching and maternal and pregnancy-related factors, compared with vaginal delivery, birth by cesarean delivery was not significantly associated with early-onset colorectal cancer in the overall population (adjusted odds ratio [aOR] = 1.28, 95% confidence interval [CI] = 0.91–1.79).
Among females, birth by cesarean delivery was associated with a significantly increased risk of early-onset colorectal cancer (aOR = 1.62, 95% CI = 1.01–2.60). Among males, birth by cesarean delivery was not associated with a significantly increased risk (aOR = 1.05, 95% CI = 0.64–1.72).
Among females, increased risk was similar in analyses limited to those aged ≥ 35 years at the index date (aOR = 2.13, 95% CI = 1.02–4.48); those without a maternal history of cesarean delivery (aOR = 1.63, 95% CI = 1.00–2.66); and those without a maternal history of diabetes, gestational diabetes, hypertension, preeclampsia, or inflammatory bowel disease (aOR = 1.70, 95% CI = 1.05–2.74).
The investigators concluded, “In this nationwide, population-based, case-control study, birth by cesarean delivery was not associated with early-onset colorectal cancer compared with birth by vaginal delivery in the overall population in Sweden. However, females born by cesarean delivery had greater odds of early-onset colorectal cancer compared with individuals born through vaginal delivery. This finding suggests that early-life gut dysbiosis may contribute to early-onset colorectal cancer in females.”
Jonas F. Ludvigsson, MD, PhD, of the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, is the corresponding author for the JAMA Network Open article.
Disclosure: The study was supported by the U.S. National Cancer Institute, Swedish Cancer Foundation, and others. For full disclosures of the study authors, visit jamanetwork.com.
