Frequent allelic loss at chromosome 3p distinct from genetic alterations of the 8-oxoguanine DNA glycosylase 1 gene in head and neck cancer

Cigarette smoking is the major known risk factor for head and neck cancer. Tobacco promotes oxidative stress and enhances tissue levels of 8-hydroxygu anine (8-OH-G) in smokers. The presence of 8-OH-G does not impede replicati on but leads to an accumulation of G --> T transversions. Recently, the gen e for human 8-oxoguanine DNA glycosylase 1 (hOGG1), an enzyme involved in t he repair of 8-OH-G in humans, was cloned and mapped to chromosome 3p. In h ead and neck tumors, the hOGG1 gene locus is often targeted by loss of hete rozygosity (LOH), and the spectrum of mutations in the p53 gene shows a bia s in favor of G:C --> T:A transversions, as would be expected if HOGG1 repa ir functions were disabled. To test the involvement of hOCG1 in head and ne ck carcinogenesis, we had previously screened 56 tumors for LOH at 3p. From these tumors and two others, we selected 33 tumors demonstrating LOH for f urther mutational analysis of this gene. No somatic inactivating mutation w as found in hOGG1. Polymorphisms involving intron 4 and exon 7 were present in 30% of the patients. A new polymorphism was identified in one patient i n exon 6 and led to the amino-acid change G308E. Similar repair activities were found for the wild-type and exon 6-variant enzymes. Therefore, the inv olvement of hOGG1 in head and neck carcinogenesis is not strongly supported by this work. Mol. Carcinog. 26:254-260, 1999. (C) 1999 Wiley-Liss, Inc.