Bilirubin and risk of ischemic heart disease in Korea: a two-sample Mendelian randomization study.

OBJECTIVES: Bilirubin is an endogenous antioxidant that protects cells against oxidative stress. Increased plasma levels of bilirubin have been associated with a reduced risk of ischemic heart disease (IHD) in previous studies. Nonetheless, whether those associations reflect a true protective effect of bilirubin on IHD, rather than confounding or reverse causation, remains unknown. Therefore, we applied two-sample Mendelian randomization to evaluate the causal association between bilirubin levels and IHD risk in a Korean population. METHODS: A total of 5 genetic variants-TRPM8 (rs10490012), USP40 (rs12993249), ATG16L1 (rs2119503), SLCO1B1 (rs4149014), and SLCO1B3 (rs73233620)-were selected as genetic instruments for serum bilirubin levels using a communitybased cohort, the Korean Genome and Epidemiology Study, comprising 33,598 subjects. We then evaluated their impact on IHD using the Korean Cancer Prevention Study-II cohort. RESULTS: Among the 5 instrumental variables that showed significant associations with serum bilirubin levels, rs12993249 (USP40) showed the most significant association (p<2.36×10-105). However, we found no significant association between serum bilirubin levels and IHD. Sensitivity analyses demonstrated a consistent association, suggesting that our observations were robust. CONCLUSIONS: Using two-sample Mendelian randomization, we found no association between serum bilirubin levels and IHD. Further studies that confirm the observed interactions among other ethnicities are warranted.

Association between smoking and gout: a meta-analysis.

Previous studies showed that smoking is linked with the decreased risk of gout, but the results remain controversial. The aim of this meta-analysis was to determine the associations between smoking and the risk of gout. A systematic literature search of PubMed and EMBASE was conducted. Data were extracted by two independent reviewers. The pooled odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of associations, using random effects and fixed effects models. Five studies with a total of 17,915,507 participants with 16,880 gouts were enrolled. Heterogeneity among the effect sizes of five studies was reported as I2 = 87.9%. Our meta-analysis indicated that smoking (ever- vs non-, OR = 0.87, 95% CI = 0.67-1.12) was not associated with the risk of gout in random effects model, whereas there was an association between smoking (ever- vs non-, OR = 0.70, 95% CI = 0.65-0.74) and gout risk in fixed effects model. Our finding indicates that smoking may not be involved in the risk of gout. However, further studies are still needed to confirm our results.

E-cigarettes, conventional cigarettes, and dual use in Korean adolescents and university students: Prevalence and risk factors.

OBJECTIVE: To examine risk factors associated with use of e-cigarettes only, conventional cigarettes only, and dual use in Korean adolescents and young adults. METHODS: In a cross-sectional study, anonymous questionnaires were completed between April-May, 2015 among 1) 2744 middle and high school students, aged 13-18, from Seoul, Incheon, Gyeonggi, and Cheongju, Korea and 2) 2167 university students, aged 19-29, from fourteen universities in Korea. RESULTS: The results show that 12.6% of adolescents and 21.2% of university students reported having ever tried e-cigarettes at least once. Among the ever e-cigarette users, 95.1% and 96.3% of adolescents and university students also tried conventional cigarettes, respectively. Dual users were more likely to be male (adolescents: OR 2.63, 95% CI 1.93-3.57; university students: 4.28, 3.21-5.70), have any close friends who smoke (adolescents: 11.56, 7.63-17.53; university students: 11.29, 5.52-23.10), have any siblings who smoke (adolescents: 3.17, 2.25-4.46; university students: 1.78, 1.30-2.43), and have observed teachers smoke cigarettes at school (adolescents: 1.45, 1.05-2.01). CONCLUSIONS: A majority of e-cigarette users were dual users. Friends' and siblings' smoking status were significantly associated with dual product use in adolescent and young adult populations. Surveillance of e-cigarette use and implementation of evidence-based behavioral interventions targeting adolescents and young adults are necessary.

Tuberculosis, smoking and risk for lung cancer incidence and mortality.

Among the exposures associated with risk for lung cancer, a history of tuberculosis (TB) is one potentially important factor, given the high prevalence of TB worldwide. A prospective cohort study was conducted to evaluate the associations of preexisting pulmonary TB with lung cancer incidence and mortality. The cohort consisted of 1,607,710 Korean adults covered by the National Health Insurance System who had a biennial national medical examination during 1997-2000. During up to 16 years of follow-up, there were 12,819 incident cases of lung cancer and 9,562 lung cancer deaths. Using Cox proportional hazards models and controlling for age, cigarette smoking and other covariates, the presence of underlying TB was significantly associated with increased risk for lung cancer incidence (HR 1.37 in men with 95% CI 1.29-1.45; HR 1.49 in women with 95% CI 1.28-1.74) and mortality (HR 1.43 in men with 95% CI 1.34-1.52; HR 1.53 in women with 95% CI 1.28-1.83). We also observed a dose-response relationship between number of cigarettes smoked daily and lung cancer risk. There was no evidence for synergism between a history of TB and smoking. The elevation in risk is relatively modest, particularly in comparison to that from smoking, and a prior history of TB is not likely to be useful risk indicator for clinical purposes. In populations with high prevalence of TB, it can be considered for incorporation into models for lung cancer risk prediction.

Physical Activity Level and Colorectal Cancer Mortality.

Physical activity has been shown to reduce colorectal cancer risk. However, the association of physical activity levels separately with colon and rectum cancer mortality is less clear. We included 226 089 Korean in a large prospective cohort study. We assessed the associations of physical activity levels (length, frequency, and intensity) with colon and rectum cancer mortality using Cox proportional hazards model. Men, but not women, who had regular physical activity showed a lower risk of death from colon cancer. The association for high intensity of physical activity was borderline significant in men (hazard ratio 0.67; 95% CI = 0.45-1.00 for >17.5 MET-hour/week). The associations were largely consistent among those aged <55 years, body mass index <25 kg/m2, low high-density lipoprotein cholesterol, current smoker, and without hypertension or history of cardiovascular disease. In conclusion, higher length or intensity of physical activity decreased colon, but not rectum cancer mortality in men. Regular physical activity may have beneficial effects on colon cancer survival.

The effect of smoking on lung cancer: ethnic differences and the smoking paradox.

The objectives of this review were to determine whether the smoking paradox still exists and to summarize possible explanations for the smoking paradox. Based on published data, we compared the risk of cigarette smoking for lung cancer in Western and Asian countries. We extracted data from the relevant studies about annual tobacco consumption, lung cancer mortality rates according to smoking status from each country, and possible explanations for the smoking paradox. A significantly greater risk of lung cancer death was found among current smokers in Asian countries than among nonsmokers, with relative risks (RRs) of 4.0 to 4.6 for Koreans, 3.7 to 5.1 for Japanese, and 2.4 to 6.5 for Chinese. Although a significantly greater risk of lung cancer was present among current smokers in Asian countries, the RRs in Asian countries were much lower than those reported in Western countries (range, 9.4 to 23.2). Possible explanations for the smoking paradox included epidemiologic characteristics, such as the smoking amount, age at smoking initiation, and the use of filtered or mild tobacco. The smoking paradox definitely exists, but may be explained by major epidemiologic characteristics. Therefore, the smoking paradox should not be interpreted as indicating that tobacco is safer or less harmful for Asians.

A colorectal cancer prediction model using traditional and genetic risk scores in Koreans.

BACKGROUND: Genome-wide association studies have identified numerous single nucleotide polymorphisms (SNPs) as associated with colorectal cancer (CRC) risk in populations of European descent. However, their utility for predicting risk to CRC in Asians remains unknown. A case-cohort study (random sub-cohort N=1,685) from the Korean Cancer Prevention Study-II (KCPS-II) (N=145,842) was used. Twenty-three SNPs identified in previous 47 studies were genotyped on the KCPS-II sub-cohort members. A genetic risk score (GRS) was calculated by summing the number of risk alleles over all SNPs. Prediction models with or without GRS were evaluated in terms of the area under the receiver operating characteristic curve (AUROC) and the continuous net reclassification index (NRI). RESULTS: Seven of 23 SNPs showed significant association with CRC and rectal cancer in Koreans, but not with colon cancer alone. AUROCs (95% CI) for traditional risk score (TRS) alone and TRS plus GRS were 0.73 (0.69-0.78) and 0.74 (0.70-0.78) for CRC, and 0.71 (0.65-0.77) and 0.74 (0.68-0.79) for rectal cancer, respectively. The NRI (95% CI) for a prediction model with GRS compared to the model with TRS alone was 0.17 (-0.05-0.37) for CRC and 0.41 (0.10-0.68) for rectal cancer alone. CONCLUSION: Our results indicate genetic variants may be useful for predicting risk to CRC in the Koreans, especially risk for rectal cancer alone. Moreover, this study suggests effective prediction models for colon and rectal cancer should be developed separately.