Liver cancer is the sixth most commonly occurring cancer in the world and the second leading cause of cancer death. Although relatively rare, the incidence of liver cancer has been rising rapidly in the United Kingdom. Notably, in almost all areas worldwide, the incidence rate of liver cancer is two- to three-fold higher in men than women, which may be partially explained by sex-specific prevalence of risk factors. Prolactin is a protein hormone that is expressed at higher levels in women than men. Prolactin is best known for its effects on the mammary gland, but it also has a variety of other biological functions, including its regulation of immune responses. One study found that in mice, prolactin prevented hepatocellular carcinoma (HCC) by restricting innate immune activation of c-myc. The use of domperidone, an anti-dopamine drug that has a prolactin-releasing effect, was found to prevent HCC in tumor-prone male mice. To our knowledge, the association of domperidone use with liver cancer risk has not been reported in population studies. Thus, we propose to conduct a case-control study of primary liver cancer in relation to domperidone use.
We aim to conduct a case-control study to assess the association between use of domperidone and the subsequent development of liver cancer among individuals in the CPRD. We will identify all eligible primary liver cancer cases in this population, and controls will be matched to cases at a 4:1 ratio on age, sex, general practice, and length of time in the CPRD. Ever-use of domperidone will be defined as having at least 2 prescriptions during the study period, and non-use will be defined as having 0 or 1 prescriptions during the study period. We will additionally classify use of domperidone according to duration and total number of prescriptions received. We will use conditional logistic regression to assess crude and adjusted risk estimates (odds ratios [ORs] and 95% confidence intervals [CIs]) for use of domperidone and the risk of developing liver cancer. In addition to variables controlled through matching, a comprehensive list of potential confounders will be evaluated.
Katherine McGlynn - Chief Investigator - National Institutes of Health - USA
Katherine McGlynn - Corresponding Applicant - National Institutes of Health - USA
Baiyu Yang - Collaborator - Roche
Barry I Graubard - Collaborator - National Cancer Institute ( NCI )