Females born by cesarean delivery may be at greater risk of early-onset colorectal cancer: JAMA

However, females born by cesarean delivery had greater odds of early-onset CRC than those born through vaginal delivery, suggesting that early-life gut dysbiosis may lead to early-onset CRC in females. When stratified by sex, the investigators found a 62% increase in early-onset CRC in females born by caesarean delivery but not in males.

There has been a rise in the incidence of early-onset colorectal cancer diagnosed before 50 years of age. The leading mechanism hypothesized is gut dysbiosis throughout life, but epidemiologic data are limited. To fill this knowledge gap, Yin Cao, Washington University School of Medicine, St Louis, Missouri, and colleagues prospectively examined the association between birth by cesarean delivery and early-onset colorectal cancer among offspring.

For this purpose, the researchers identified adults diagnosed with colorectal cancer between 18 and 49 years of age from 1991 to 2017 through the ESPRESSO cohort. Matching of 5 general population control individuals without CRC was done with each case on sex, age, country of residence, and calendar year. Pathology-confirmed endpoints were linked with the Swedish Medical Birth Register and other national registers.

The development of early-onset colorectal cancer in the overall population and by sex was determined (primary outcome).

The study revealed the following findings:

• Five hundred sixty-four case patients with incident early-onset CRC were identified (mean age, 32.9 years; 50.4% male) and 2180 matched controls (mean age, 32.7 years; 50.6% male).
• Compared with vaginal delivery, birth by cesarean delivery was not associated with early-onset CRC in the overall population (adjusted odds ratio [aOR], 1.28) after multivariable adjustment for matching and maternal and pregnancy-related factors.
• A positive association was found for females (aOR, 1.62) but no association for males (aOR, 1.05).

The researchers note that the Swedish case-control study is among the first to provide epidemiological support to the gut dysbiosis hypothesis behind early-onset CRC. It found that females born via cesarean delivery had greater odds of developing early-onset CRC than those born through vaginal delivery, but there was no association among males.

"The finding of a gender difference may be attributed to female sex hormones influencing interactions between the enteric immune system, microbial signalling, and mucosal barrier functioning," they wrote.

Reference:

Cao Y, Nguyen LH, Tica S, et al. Evaluation of Birth by Cesarean Delivery and Development of Early-Onset Colorectal Cancer. JAMA Netw Open. 2023;6(4):e2310316. doi:10.1001/jamanetworkopen.2023.10316