Little is known about longitudinal associations of exercise with different types of cancer, particularly in Asian populations. The purpose of this research was to estimate the association between the duration of exercise and all-cause and cancer-specific mortality. Data were obtained from the Korean Metabolic Syndrome Mortality Study (KMSMS), a prospective cohort study of 303,428 Korean adults aged 20 years or older at baseline between 1994 and 2004 after exclusion of individuals with missing variables on smoking and exercise. Death certificate-linked data until 31 December 2015 were provided by the Korean National Statistical Office. Cox regression models were constructed to evaluate the associations of exercise with cancer mortality after adjusting for potential confounders such as age, alcohol consumption and smoking status. During the follow-up period of 15.3 years (4,638,863 person-years), a total of 16,884 participants died. Both men and women who exercised showed approximately 30% decreased hazards of mortality, compared to those who did no exercise (hazard ratio (HR) 0.70, 95% confidence interval (CI)=0.68-0.73 for men, HR=0.71, CI : 0.67-0.75). A notable observation of this study is the curvilinear associations between the total duration of exercise per week and cancer mortality, with the lowest risk being observed at the low-to-medium levels of exercise; this trend of associations was found for esophagus, liver, lung, and colorectal cancer mortality in men, and all-cause, all-cancer and lung cancer mortality in women. Individuals who exercised showed considerably lower all-cause and cancer mortality risks compared with those who did no exercise. Policies and clinical trials aimed at promoting minimal or moderate participation in exercise may minimize cancer mortality risk.

Introduction: Smoking among young adults is associated with atherosclerotic cardiovascular disease (ASCVD) in middle age. Our aim was to analyze the trajectory of smoking in young adults and analyze the effects of the trajectory group on incident ASCVD. Methods: This study was conducted among 60,709 young adult men aged 20–29 years who received health screening every two years from 1992–2004. Trajectory analysis was performed through smoking survey data measured 7 times during this period. ASCVD, including ischemic heart disease (IHD) and stroke events were confirmed from 2005–2015. The association between the trajectory group and ASCVD risk was analyzed using Cox proportional hazard models, controlling for covariates and mediators. Results: Trajectory analysis showed that smoking categorized into five groups as follows: Group 1 (28.3%), low steady; Group 2 (14.7%), lowering; Group 3 (17.3%), high steady; Group 4 (15.6%), rise and fall; and Group 5 (24.2%), very high steady. The model performance of the trajectory model (Akaike information criterion; AIC = 51,670.78) with mediators was better than the model (AIC = 51,847.85) without mediators. Group 5 showed a 49% higher risk of ASCVD than Group 1. The risk of IHD was 1.63-times higher for Group 5 and 1.31-times higher for Group 4, compared to Group 1. Compared to Group 1, Group 5 had a 1.36- and 1.58-times higher risk for total stroke and ischemic stroke, respectively. Conclusions: In young adult men, the multiple measured trajectory model with mediators was far more informative than one-time smoking for explaining the association with cardiovascular disease.

High LDL-cholesterol (LDL-C) is a well-known risk factor for coronary artery disease (CAD). PCSK9, HMGCR, NPC1L1, ACLY, and LDLR gene have been reported as lipid lowering drug genes related to LDL-C lowering. However relevant Asian studies were rare. We examined the causality between LDL-c drug target genes and CAD using Korean and Japanese data using the two sample Mendelian Randomization (MR) method. We conducted two-sample MR analysis of LDL-c lowering drug target genes (7 Single-nucleotide polymorphisms (SNP) in PCSK9, 6 SNPs in HMGCR, 5 SNPs in NPC1L1, 9 SNPs in ACLY, 3 SNPs in LDLR) and CAD. We used summary statistics data from the Korean Genome Epidemiology Study (KOGES) for LDL-C data, and Biobank of Japan (BBJ) for CAD data. For every 10 mg/dl decrease in LDL-C determined by four significant SNPs in the PCSK9 gene, the risk of CAD decreased by approximately 20% (OR = 0.80, 95% CI: 0.75–0.86). The risk of CAD decreased by 10% for every 10 mg/dl decrease in LDL-C due to the six significant SNPs in the HMGCR gene (OR = 0.90, 95% CI: 0.86–0.94). Due to the two significant SNPs in the gene LDLR, the risk of CAD decreased by approximately 26% for every 10 mg/dl decrease in LDL-C (OR = 0.74, 95% CI: 0.66–0.82). The combined effect on CAD showed the largest effect size for the PCSK9 gene and LDLR gene, and the reduced CAD risk induced by these two genes together was OR = 0.78 (95%CI, 0.74–0.83). Finally, the combined effect of all three genes (PCSK9, HMGCR, and LDLR) was OR = 0.85 (95%CI, 0.79–0.91). LDL-C reduction estimated by SNPs in LDL-C lowering drug target genes significantly reduced the risk of CAD. We found the potential of using of proxy research design for clinical trials using LDL-C lowering drugs.