Background: The goal of chemoprevention is to reduce the risk of cancer development by reversing or blocking the tu-morigenic process through the use of pharmacologic or natu-ral agents. To determine the potential role of genetic alter-ations in assessing cancer risk and in evaluating the efficacy of chemopreventive agents, we studied 22 patients with ad-vanced premalignant lesions of the head and neck who were part of a prospective cancer prevention trial that is investi-gating a regimen of 13-cis-retinoic acid, interferon alfa, and a-tocopherol administered for 12 months or until disease progression. Methods: We used polymerase chain reaction analysis of microsatellite DNA sequences in cells from pre-cancerous lesions to determine the frequencies of genetic alterations—namely, loss of heterozygosity (LOH) and mic-rosatellite instability—at chromosomal loci that are com
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