Gender differences in smoking-induced DNA damage.

B54

Background: Oxidative reactions have been implicated as important modulators of human health and can play a role in both disease prevention and disease development. A large number of studies have demonstrated an increased oxidant burden and consequently increased markers of oxidative stress in the blood, and urine of patients with chronic obstructive pulmonary disease (COPD).The overall goal of this study is to explore the association between urinary markers of DNA damage as measured by 8-hydroxydeoxyguanosine ( 8-OhDG), antioxidant enzymes, and FEV1/FVC among smokers and former smokers with different levels of pulmonary obstruction. Methods : Cross-sectional analysis of data from baseline samples from participants in an ongoing chemoprevention trial. The study participants provided blood and urine samples which were used for the analysis of 8-OHdG, superoxide dismutase (SOD) and catalase (CAT) levels. All statistical analyses (descriptive & linear regressions) were performed using STATA. Results : The study protocol was approved by all parties in April 2004. A total of 119 COPD (mean FEV1/FVC = 65.7 ± 13.5) subjects (61 females and 58 males)were included in the study. Fifty nine percent were former smokers and 41% current smokers, with a mean pack year of 49.2±23.5. Urinary 8-OHdG levels were significantly associated with sex (p=0.0008), with females having higher levels of DNA damage regardless of theis smoking status or pack/years. Catalase levels were significantly associated with pack years (p=0.019) when sex was also considered (p=0.057). SOD levels were not associated with any of the studied variables. As expected FEV1/FVC was significantly associated with pack years in the study population (p=0.0058), however, this association was mainly significant among males (p=0.0489) compared to females(p=0.2023). Conclusions : Among older adult smokers and former smokers, females have higher levels of DNA damage than males as measured by urinary 8-OHdG even after controlling for smoking. Catalase activity has a negative association with pack years, and is lower among female subjects. FEV1/FVC was associated with pack years - as we expected more smoking is associated with lower lung function - but more significantly among males No significant relationship between FEV1/FVC and pack years was found among females. In summary, it seems that female smokers are much more prone to oxidative stress as compared to male smokers. More studies are needed to explore the role of gender in susceptibility to DNA damage among smokers.