No evidence of association between methyldopa and biliary carcinoma.

Abstract

Cancer of the bile ducts is rare and little is known about its risk factors. Recently, an association between methyldopa therapy and biliary carcinoma was reported in a retrospective case-control study. If this association were real, it would represent a significant health hazard, because methyldopa is widely prescribed. Using analysis of covariance to study the relationship between biliary tract cancer rates (obtained from 11 cancer registries in the US, Canada, Europe, and Asia) and per capita methyldopa sales (obtained from its manufacturer), this possible association was re-examined. For the rates of all biliary tract cancers combined, using both three- and ten-year lag periods between drug sales and disease, there were no associations between methyldopa and biliary carcinoma. When the rates for the biliary tract cancer sites were examined separately, one small positive regression coefficient was observed with extrahepatic biliary tract cancer, using the ten-year lag period only (p = 0.03). Since the majority of biliary tract cancers are extrahepatic in origin, it is likely that most of the cancers coded as 'biliary tract cancer, part unspecified' are actually extrahepatic. Also, the magnitude of the slope is very small, contrary to what one would expect with a common drug exposure and an uncommon disease. For these reasons, we believe that the negative results obtained with the combined rates for biliary tract cancer are more meaningful than the results obtained for each cancer site separately. In conclusion, our data do not support the presence of an association between methyldopa and biliary tract cancer.