Smoking-Related DNA Methylation is Differentially Associated with Cadmium Concentration in Blood.

Tobacco smoking, a risk factor for several human diseases, can lead to alterations in DNA methylation. Smoking is a key source of cadmium exposure; however, there are limited studies examining DNA methylation alterations following smoking-related cadmium exposure. To identify such cadmium exposure-related DNA methylation, we performed genome-wide DNA methylation profiling using DNA samples from 50 smokers and 50 non-smokers. We found that a total of 136 CpG sites (including 70 unique genes) were significantly differentially methylated in smokers as compared to that in non-smokers. The CpG site cg05575921 in the AHRR gene was hypomethylated (Δ ß > - 0.2) in smokers, which was in accordance with previous studies. The rs951295 (within RNA gene LOC105370802) and cg00587941 sites were under-methylated by > 15% in smokers, whereas cg11314779 (within CELF6) and cg02126896 were over-methylated by ≥ 15%. We analyzed the association between blood cadmium concentration and DNA methylation level for 50 smokers and 50 non-smokers. DNA methylation rates of 307 CpG sites (including 207 unique genes) were significantly correlated to blood cadmium concentration (linear regression P value < 0.001). The four significant loci (cg05575921 and cg23576855 in AHRR, cg03636183 in F2RL3, and cg21566642) were under-methylated by > 10% in smokers compared to that in non-smokers. In conclusion, our study demonstrated that DNA methylation levels of rs951295, cg00587941, cg11314779, and cg02126896 sites may be new putative indicators of smoking status. Furthermore, we showed that these four loci may be differentially methylated by cadmium exposure due to smoking.

Polycyclic aromatic hydrocarbon-induced oxidative stress, antioxidant capacity, and the risk of lung cancer: a pilot nested case-control study.

AIM: We conducted a pilot nested case-control study to prospectively evaluate the effects of polycyclic aromatic hydrocarbons (PAH) exposure, antioxidant capacity, and oxidative stress on lung carcinogenesis. MATERIALS AND METHODS: Thirty-five patients with lung cancer and 140 age- and sex-matched controls were selected from a sub-cohort of the Korean Multi-center Cancer Cohort. PAH metabolites (1-hydroxypyrene and 2-naphthol), oxidative stress markers, and total antioxidant capacity (TAC) were assessed using urine samples collected at baseline. RESULTS: The levels of urinary PAH metabolites and oxidative stress were not different between cases and controls. Urinary 1-hydroxypyrene and 2-naphthol levels were significantly associated with urinary oxidative stress markers only in lung cancer cases. Individuals with low urinary TAC and high urinary oxidative stress levels had significantly higher risk of lung cancer compared to those with high urinary TAC and low urinary oxidative stress levels. CONCLUSION: Oxidative stress induced by PAH exposure and TAC may be important determinants for the susceptibility to lung cancer.