Domperidone use and risk of primary liver cancer in the Clinical Practice Research Datalink

Cancer Epidemiol. 2018 Aug:55:170-175. doi: 10.1016/j.canep.2018.06.009. Epub 2018 Jul 6.

Abstract

Background: Pronounced sex-disparity in liver cancer suggests a role for hormones, one of which could be prolactin. Stimulation of prolactin production in mice via domperidone has been reported to decrease hepatocarcinogenesis, thus may have chemopreventive potential. To study the effect of domperidone in humans, a large medical records study was conducted.

Methods: Based in the Clinical Practice Research Datalink, 1921 liver cancer cases and 7681 controls were identified. Conditional logistic regression was employed to estimate odds ratios (OR) and 95% confidence intervals (CI). Domperidone use was analyzed overall, and by number of prescriptions and cumulative dose.

Results: Comparing ever- versus never-use, there was no association between domperidone and liver cancer among men (OR = 1.06, 95% CI: 0.76-1.48) or women (OR = 1.21, 95% CI: 0.82-1.76). Among men, there was no association with dose or number of prescriptions, while among women who received the highest doses (OR2700 mg vs. 0 mg = 2.52, 95% CI: 1.18-5.41, p-trend = 0.02) and greatest number of prescriptions (OR≥11 Rx vs. 0 Rx = 3.17, 95% CI: 1.07-9.40, p-trend = 0.02) there was a significantly increased risk, although there was no evidence of heterogeneity in the results by gender.

Conclusion: Domperidone use was not associated with decreased liver cancer risk among all study participants. Among women, an increased risk at highest levels of exposure warrants further study.

Keywords: CPRD; Domperidone; Hormones; Liver cancer; Prolactin; Sex-discrepancy; Sex-disparity.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Biomedical Research*
  • Case-Control Studies
  • Databases, Factual*
  • Domperidone / adverse effects*
  • Dopamine Antagonists / adverse effects*
  • Female
  • Humans
  • Liver Neoplasms / chemically induced*
  • Liver Neoplasms / epidemiology*
  • Male
  • Middle Aged
  • Practice Patterns, Physicians'*
  • Prognosis
  • Risk Factors
  • United States / epidemiology

Substances

  • Dopamine Antagonists
  • Domperidone