HOGG1 Genotype, Green Tea and Oxidative DNA Damage among Heavy Smokers

Abstract

DNA is susceptible to damage by reactive oxygen species, and 8-hydroxydeoxyguanosine (8-OHdG) is probably one of the most abundant DNA lesions formed during oxidative stress. Several pathways exist for the removal or repair of this lesion from mammalian DNA. The most established is via the base excision repair enzyme, human 8-oxoguanine glycosylase (hOGG1). Several polymorphisms in the hOGG1 gene have been detected in human populations. We were interested in whether there were differences in increased oxidative stress susceptibility to smoking within the hOGG1 genotypes and the impact of high tea drinking on this. A phase IIb randomised, controlled, tea intervention trial was designed to study the effect of high consumption (four cups per day) of decaffeinated green or black tea on oxidative DNA damage, as measured by urinary 8-OHdG, among smokers over a 4-month period and to evaluate the role of the hOGG1 genotype as an effect modifier. A total of 120 smokers with hOGG1 data completed the 4-month intervention. The hOGG1 genotype status was determined with a polymerase chain reaction-based approach. Multiple linear regression models were used to estimate the main effects and interaction effect of green and black tea consumption on creatinine-adjusted urinary 8-OHdG, with or without adjustment for potential confounders. Finally, we studied whether the effect of treatment varied by hOGG1 status of the individual. Assessment of urinary 8-OHdG after adjustment for baseline measurements and other potential confounders revealed a highly significant decrease in urinary 8-OHdG after 4 months of drinking decaffeinated green tea (p = 0.001). No change in urinary 8-OHdG was seen among smokers assigned to the black tea group. We found the distribution of hOGG1 Ser326Cys genotypes among smokers to be 62%, 28% and 10% for Ser/Ser, Ser/Cys and Cys/Cys genotypes, respectively. Because the homozygous Cys/Cys genotype was present in only 10% of the study population, the mutant types (Ser/Cys and Cys/Cys) were combined and compared with the Ser/Ser genotype. We found no significant interaction between smoking, hOGG1 genotypes and tea intervention in terms of levels of urinary 8-OHdG. This finding suggests that green tea intervention might be effective in decreasing levels of urinary 8-OHdG among smokers regardless of their hOGG1 genotype.