Glutathione peroxidase is a
selenium-containing,
antioxidant enzyme previously implicated in the risk and development of lung and
breast cancer, in part the result of allelic loss at the GPx-1 locus. This study examined allelic loss at the same locus in
squamous cell carcinomas of the head and neck. The frequency of a polymorphism at
codon 198 resulting in either a
leucine or a
proline at that position was surveyed by comparing 133
DNA samples obtained from head and neck
tumors and 517 samples obtained from
cancer-free individuals.
Tumor DNAs exhibited fewer
pro/leu heterozygotes as compared to
DNA obtained from the
cancer-free population. Fewer GPx-1 heterozygotes were verified by determining the frequency of highly polymorphic
alanine repeat sequences in the same gene. The analysis revealed an approximately 42% reduction in heterozygosity in the
DNA from the
tumor samples. In order to assess loss of heterozygosity (LOH) at the GPx-1 locus,
DNA was genotyped from peripheral lymphocytes,
tumor tissue, and microscopically normal tissues adjacent to the
tumor, derived from the same patients. These studies indicated LOH at the GPx-1 locus in each of the three
tumor/normal tissues sample sets examined. Furthermore, LOH in the microscopically normal tissues at the
tumor margin occurred in two of the three sample sets examined. These data implicate GPx-1 in the development of
squamous cell carcinoma the head and neck and suggest that allelic loss of this gene, or one tightly linked to it, is an early event in the development of this type of
malignancy.