In Utero exposure to Dicyclomine tied to increased risk of colorectal cancer among offsprings

According to a journal article published in JNCI Cancer Spectrum entitled "In utero exposure to anti-emetic and risk of adult-onset colorectal cancer”, researchers have concluded that the Higher Risk of CRC in offspring exposed in utero may be driven by dicyclomine contained in the three-part formulation of Bendectin used during the 1960s.

Among adults born in and after 1960, there are increasing incidence rates of colorectal cancer (CRC). This implicates pregnancy-related exposures as a risk factor introduced at that time. In 1960, dicyclomine was initially introduced as an antispasmodic for managing irritable bowel syndrome. It was used in Bendectin (doxylamine/pyridoxine/dicyclomine), which is an anti-emetic. This was prescribed during pregnancy in the 1960s.

A team of researchers estimated this association and enrolled pregnant women in Oakland, CA, between 1959 and 1966, including 14,507 mothers and 18,751 liveborn offspring.

The prescribed medications were reviewed from mothers’ medical records to identify those who received Bendectin during pregnancy. Diagnoses of CRC in adult (age ≥18 years) offspring were ascertained by linkage with the California Cancer. The adjusted hazard ratios (aHR) were estimated with follow-up accrued from birth through cancer diagnosis, death, or last contact.

The study results could be summarised as follows:

• A total of 1014 offspring constituting 5% of offspring, were exposed in utero to Bendectin.
• The Risk of colorectal cancer or CRC was higher in offspring exposed in utero with aHR of 3.38 than in unexposed offspring.
• CRC incidence rates in offspring exposed to Bendectin and unexposed were 30.8 and 10.1 per 100,000, respectively.

In conclusion, Murphy et al. said, “We reported a higher risk of Colorectal cancer in offspring exposed in utero. This Risk may be driven by dicyclomine, one of the ingredients contained in the three-part formulation of Bendectin, which was used in the 1960s.”

Further studies are warranted to clarify these findings and identify mechanisms of Risk.

Further reading:

Caitlin C Murphy, PhD, MPH, Piera M Cirillo, MPH, Nickilou Y Krigbaum, MPH, Amit G Singal, MD, MS, Barbara A Cohn, PhD, In utero exposure to anti-emetic and risk of adult-onset colorectal cancer, JNCI Cancer Spectrum, 2023; pkad021, https://doi.org/10.1093/jncics/pkad021