Leanness, Smoking, and Enhanced Oxidative DNA Damage

Abstract

An increased risk of some forms of cancer, including lung cancer, among lean individuals has been consistent; however, there is a paucity of biological evidence supporting this relation. Subjects analyzed were 177 healthy Japanese workers who participated in a lifestyle intervention study. The levels of urinary 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative DNA damage, were measured using an automated high-pressure liquid chromatography and urinary creatinine levels were adjusted for before statistical analysis. A clear inverse association was found between body mass index (BMI) and 8-OHdG levels among smokers [Pearson correlation coefficient (r) = À0.48], and the association did not materially change after adjustment for potential confounding factors. In contrast, no apparent relation was observed between BMI and 8-OHdG levels among nonsmokers (r = À0.12), although lean nonsmokers had a slightly higher mean of 8-OHdG levels compared with nonlean nonsmokers. The interaction of smoking and BMI reached statistical significance (P = 0.04). Leanness may enhance oxidative DNA damage induced by smoking and thus serve as a marker of host susceptibility to smoking-related cancers. (Cancer Epidemiol Biomarkers Prev 2006;15(3):582 -5)

Body mass index and oxidative DNA damage: A longitudinal study

“…Moreover, a modifying effect of smoking on their relationship was also suggested. (8,11) These findings are in accordance with the leanness-cancer hypothesis; however, causal inference is limited by the cross-sectional nature of the study design. We took 8-OHdG measurements on two additional occasions during the follow-up period for the participants in the above-mentioned study.…”

“…We took 8-OHdG measurements on two additional occasions during the follow-up period for the participants in the above-mentioned study. (11) Here, we report a longitudinal association of BMI and body fat with 8-OHdG levels.…”

“…Moreover, because smoking is related to lower BMI levels, (6) the increased risk of cancer associated with leanness may reflect smoke-induced weight loss. Biological evidence linking leanness to carcinogenesis may provide a clue to this issue.Oxidative DNA stress is thought to play a major role in carcinogenesis, (7) and increased levels of 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative DNA damage, have been detected in the urine of smokers (8,9) and in lung cancer tissue.(10) Our previous analysis using baseline data of an intervention study (11) as well as other cross-sectional studies (8,9) have reported an inverse association between BMI and urinary 8-OHdG levels. Moreover, a modifying effect of smoking on their relationship was also suggested.…”

“…(10) Our previous analysis using baseline data of an intervention study (11) as well as other cross-sectional studies (8,9) have reported an inverse association between BMI and urinary 8-OHdG levels. Moreover, a modifying effect of smoking on their relationship was also suggested.…”

Body mass index and smoking-related lung cancer risk in the Singapore Chinese Health Study

“…It is biologically plausible that leanness may modulate the carcinogenic effects of smoking directly. Cross sectional and longitudinal studies have shown that both BMI itself and the decrease in BMI inversely correlated with the level of urinary 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative DNA damage in smokers, suggesting that BMI may serve as an independent marker for host susceptibility to smokingrelated cancer (Loft et al, 1992;Mizoue et al, 2006Mizoue et al, , 2007. Smoking may induce weight loss by increasing the metabolic rate, which also leads to higher production of cellular-reactive species, a carcinogenic pathway that is, therefore, enhanced among lean smokers (Loft et al, 1992).…”