In utero exposure to anti-emetic and risk of adult-onset colorectal cancer
Menée à partir de données 1959-1966 de registres californiens portant sur plus de 18 000 dyades mère-enfant(s), cette étude analyse l'association entre une exposition in utero aux antiémétiques et le risque, pour l'enfant, de développer un cancer colorectal à l'âge adulte
Incidence rates of colorectal cancer (CRC) are increasing among adults born in and after the 1960s, implicating pregnancy-related exposures introduced at that time as risk factors. Dicyclomine, an antispasmodic used to treat irritable bowel syndrome, was initially included in Bendectin (doxylamine/pyridoxine/dicyclomine), an anti-emetic prescribed during pregnancy in the 1960s.We estimated the association between in utero exposure to Bendectin and risk of CRC in offspring of the Child Health and Development Studies, a multi-generational cohort that enrolled pregnant women in Oakland, CA between 1959 and 1966 (n = 14,507 mothers and 18,751 liveborn offspring). We reviewed prescribed medications 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 Registry. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHR), with follow-up accrued from birth through cancer diagnosis, death, or last contact.About 5% of offspring (n = 1,014) were exposed in utero to Bendectin. Risk of CRC was higher in offspring exposed in utero (aHR 3.38, 95% CI 1.69, 6.77) compared to unexposed offspring. Incidence rates of CRC were 30.8 (95% CI 15.9, 53.7) and 10.1 (95% CI 7.9, 12.8) per 100,000 in offspring exposed to Bendectin and unexposed, respectively.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. Experimental studies are needed to clarify these findings and identify mechanisms of risk.