Prenatal exposure to antinausea drug associated with increased colorectal cancer risk
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Key takeaways:
- Offspring exposed to Bendectin in utero had a higher risk for developing adult-onset colorectal cancer.
- Further study is needed to determine the drug or drug combination responsible for increased risk.
In utero exposure to dicyclomine may be associated with increased risk for adult-onset colorectal cancer, results of a retrospective study suggest.
Dicyclomine, an anticholinergic used to treat irritable bowel syndrome, was part of the original three-drug formulation for Bendectin (doxylamine, pyridoxine and dicyclomine) — an antinausea medication prescribed to pregnant women during the 1960s and 1970s before being pulled from the U.S. market in 1983 for its role in causing birth defects.
Research published in JNCI Cancer Spectrum reported a threefold higher colorectal cancer incidence rate among offspring with prenatal exposure to Bendectin compared with those not exposed.
“We can’t tease apart the effect of the individual components [of Bendectin] in our study, but the years that offspring were born correspond to the time period during which the three-component version was available,” Caitlin C. Murphy, PhD, MPH, associate professor at UTHealth Houston School of Public Health, told Healio. “It’s likely that the antispasmodic included in the three-part formula is the culprit here, because it has direct effects on the [gastrointestinal] tract.”
Background
The motivation for this study came from researchers’ curiosity about factors contributing to the rise in colorectal cancer among adults, according to Murphy.
Previous studies have shown early life is a crucial period related to the development of colorectal cancer, whereas recent data have shown an increase in colorectal cancer incidence among U.S. middle-aged adults in their 50s, she added.
“This pointed us to the prenatal period as being important and we started by looking for risk factors or exposures that have been implicated in some other kind of setting,” she said. “Bendectin had been implicated in GI birth defects, so it made sense to us that there may also be an association with colorectal cancer much later in adulthood.”
Methodology
Murphy and colleges conducted a retrospective cohort study to determine whether any association existed between in utero exposure to Bendectin and increased risk for adult-onset colorectal cancer.
The investigators used data from the Child Health and Development Studies, a multigenerational cohort of mother-child parings (14,507 mothers and 18,751 liveborn offspring) who received care in Oakland, California, between 1959 and 1966 as part of the Kaiser Foundation Health Plan.
Researchers identified mothers who received Bendectin during pregnancy from medical records. They also confirmed diagnosis of colorectal cancer among adult offspring by linking records to the California Cancer Registry.
The analysis used Cox proportional hazards models to estimate adjusted HRs, with follow-up accrued from birth through cancer diagnosis, death or last contact.
Key findings
About 5% of offspring (n = 1,014) in the study cohort had in utero exposure to Bendectin. These offspring had a higher risk for developing adult-onset colorectal cancer than offspring not exposed to Bendectin (adjusted HR = 3.38; 95% CI, 1.69-6.77).
Investigators noted a colorectal cancer incidence rate for those exposed to Bendectin in utero of 30.8 (95% CI, 15.9-53.7) per 100,000 offspring compared with 10.1 (95% CI, 7.9-12.8) per 100,000 among unexposed offspring.
Clinical implications
The results are new evidence in the effort to understand causes behind the “epidemic of colorectal cancer” among middle-aged adults, according to Murphy.
“[The findings] increase awareness that medications taken during pregnancy may have long-lasting consequences for offspring,” she added.
She said determining which of the drugs in the Bendectin formulation led to increased colorectal cancer risk in offspring cannot be determined from the study results and would require further investigation to examine each drug individually and their synergistic effects when used in combination.
“As we learn more about risk factors for colorectal cancer and young people, we’re seeing they are not what we traditionally associate with the disease — things like obesity or diet,” Murphy said. “It’s much more complicated. The risk factors that may be giving rise to the cancers affecting people showing up in an oncologists’ office today are different than what we have believed for many, many years.”
For more information:
Caitlin C. Murphy, PhD, MPH, can be reached at UTHealth Houston School of Public Health, Department of Health Promotion and Behavioral Sciences, 7000 Fannin St., Suite 2618, Houston, TX 77030; email: caitlin.c.murphy@uth.tmc.edu.
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