The human OGG1 DNA repair enzyme and its association with orolaryngeal cancer risk

Abstract

The human OGG1 (hOGG1) gene encodes a DNA glycosylase that is involved in the excision repair of 8-hydroxy-2'-deoxyguanine (8-OH-dG) from oxidatively-damaged DNA. To determine whether hOGG1 plays a role in risk for orolaryngeal cancer, we screened normal orolaryngeal tissue specimens for hOGG1 expression and assessed the role of the hOGG1 Ser326Cys polymorphism in risk for orolaryngeal cancer. hOGG1 expression was determined by reverse transcription-polymerase chain reaction of total RNA from aerodigestive tract tissues, and hOGG1 genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism analysis of buccal cell DNA isolated from 169 Caucasian orolaryngeal cancer cases and 338 race-, sex- and age-matched controls. hOGG1 mRNA was detected in all aerodigestive tract tissues tested including tonsil, tongue, floor of mouth, larynx and esophagus. Significantly increased risk for orolaryngeal cancer was observed for both the hOGG1 326(Ser)/326(Cys) (odds ratio [OR] = 1.6, 95% confidence interval [CI] = 1.04-2.6) and hOGG1 326(Cys)/326(Cys) (OR = 4.1, 95% CI = 1.3-13) genotypes. Although no significant difference in risk for orolaryngeal cancer was observed for hOGG1 genotypes in never-smokers, increased risk for orolaryngeal cancer was observed for subjects with the homozygous polymorphic hOGG1 326(Cys)/326(Cys) genotype in smokers (>100 cigarettes lifetime; OR = 4.8, 95% CI = 1.3-18). Similarly, although no association was observed in never drinkers of alcohol, significantly increased risk was observed for the hOGG1 326(Cys)/326(Cys) genotype in alcohol drinkers (>1 shot/week; OR = 6.9, 95% CI = 1.6-29). These results suggest that hOGG1 may play an important role in the repair of 8-OH-dG adducts in the aerodigestive tract and that the hOGG1 Ser326Cys polymorphism plays an important role in risk for smoking- and alcohol-related orolaryngeal cancer.