Associations of biomarkers for exposure to tobacco smoke with lung cancer risk in Korea.

BACKGROUND: Nicotine metabolite ratio (NMR) can be used to predict total nicotine clearance. However, it is unknown whether NMR could be used as a marker of lung cancer risk. OBJECTIVE: To evaluate the blood metabolites of nicotine relating to the risk of developing lung cancer and investigate the combined effects of NMR and cigarette per day on the risk of lung cancer. METHODS: Among the 1,054 eligible subjects from the Korean Cancer Prevention Study-II biobank cohort, those with cotinine values below 0 ng/ml were excluded. Slow and fast metabolizer groups were defined using the median value of the NMR, calculated with the control group data, as the cut-point. RESULTS: The multivariable Cox proportional hazard models demonstrated that, the fast metabolizer group had a significantly higher risk of lung cancer than the slow metabolizer group (Adjusted HR: 2.02, 95% CI: 1.32-3.10). Fast metabolizers who smoked more than 15 cigarettes per day had an even higher risk of lung cancer (Adjusted HR: 3.51, 95% CI: 1.96-6.29) than the slow metabolizers who smoked less than 15 cigarettes per day. CONCLUSIONS: In summary, the NMR may be an effective marker for estimating tobacco-related disease risks such as lung cancer.

Two-Sample Mendelian Randomization Study of Lipid levels and Ischemic Heart Disease.

BACKGROUND AND OBJECTIVES: Associations between blood lipids and risk of ischemic heart disease (IHD) have been reported in observational studies. However, due to confounding and reverse causation, observational studies are influenced by bias, thus their results show inconsistency in the effects of lipid levels on IHD. In this study, we evaluate whether lipid levels have an effect on the risk of IHD in a Korean population. METHODS: A 2-sample Mendelian randomization (MR) study, using the genetic variants associated with lipid levels as the instrumental variables was performed. Genetic variants significantly associated with lipid concentrations were obtained from the Korean Genome and Epidemiology Study (n=35,000), and the same variants on IHD were obtained from the Korean Cancer Prevention Study-II (n=13,855). Inverse variance weighting (IVW), weighted median, and MR-Egger approaches were used to assess the causal association between lipid levels and IHD. Radial MR methods were applied to remove outliers subject to pleiotropic bias. RESULTS: Causal association between low-density lipoprotein-cholesterol (LDL-C) and IHD was observed in the IVW method (odds ratio, 1.013; 95% confidence interval, 1.007-1.109). However, high-density lipoprotein-cholesterol (HDL-C) and triglyceride (TG) did not show causal association with IHD. In the Radial MR analysis of the relationship between HDL-C, TG and IHD, outliers were detected. Interestingly, after removing the outliers, a causal association between TG and IHD was found. CONCLUSIONS: High levels LDL-C and TG were causally associated with increased IHD risk in a Korean population, these results are potentially useful as evidence of a significant causal relationship.