Hall KT, et al. – Via two randomized trials of alpha-tocopherol supplementation, investigation determined whether catechol-O-methyltransferase (COMT) exerted any pharmacogenetic impact on cancer prevention. Common COMT rs4680 (val158met), which encodes a nonsynonymous valine-to-methionine substitution, was examined for its pharmacogenetic effects in the trial in addition to a 10-year post-trial follow-up (overall) period of The Women’s Genome Health Study (N=23,294)—a decade-long alpha-tocopherol and aspirin trial. A case/control (N=2,396/2,235) subset of the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study (N=29,133) was used to corroborate the findings, with total cancers being the primary outcome. Two-sided statistical tests were performed. Statistically significant COMT by alpha-tocopherol interaction was observed, such that benefits of alpha-tocopherol among rs4680 met-allele (28.0%), but not val-allele (22.8%) homozygotes, were evident.