The most effective means of avoiding the development of
squamous cell carcinomas is the elimination of risk factors such as tobacco
smoke and alcohol and of exposure to occupational and dietary
carcinogens. In addition,
chemoprevention by
micronutrients such as
beta-carotene may be promising. However, studies verifying such effects using
cancer incidence or mortality as study endpoint are extremely costly of financial and manpower resources. Therefore, premalignant intermediate
biomarkers such as histological lesions (dysplasias/
leukoplakias/
polyps), genetic changes (DNA damage, mutations) or enzymatic changes (
protein kinase C or
ornithine decarboxylase activation) are increasingly being used as
surrogate endpoints. Even though most preneoplastic
biomarkers still need to be verified and shown to be linked to
malignancy, their use in clusters may enhance their predictability. In human trials
beta-carotene has reversed some lesions such as micronuclei,
leukoplakias and dysplasias in the oral cavity, whereas other lesions, e.g. colorectal
polyps (i.e. their recurrence after resection) have not been found to respond. But proliferation markers in the colon mucosa have been modified by
beta-carotene. Preliminary findings are also available of a potential reduction of esophageal dysplasias in a high-risk Chinese population and of
cervical dysplasias in a group of American women. The available
beta-carotene data are sufficiently encouraging to justify continuation of trials using intermediate
cancer markers.