Background: This research article investigates the age, period, and birth cohort effects on prevalence of obesity in the Korean population, with the goal of identifying key factors to inform effective public health strategies. Methods: We analyzed data from the Korea National Health and Nutrition Examination Survey, spanning 2007–2021, including 35,736 men and 46,756 women. Using the hierarchical age-period-cohort (APC) analysis with cross-classified random effects modeling, we applied multivariable mixed logistic regression to estimate the marginal prevalence of obesity across age, period, and birth cohort, while assessing the interaction between APC and lifestyle and socioeconomic factors. Results: Our findings reveal an inverted U-shaped age effect on obesity, influenced by smoking history (P for interaction = 0.020) and physical activity (I for interaction < 0.001). The period effect was positive in 2020 and 2021, while negative in 2014 (P for period effect < 0.001). A declining trend in obesity prevalence was observed in birth cohorts from 1980s onward. Notably, disparities in obesity rates among recent birth cohorts have increased in relation to smoking history (P for interaction = 0.020), physical activity (P for interaction < 0.001), and residence (P for interaction = 0.005). Particularly, those born after 1960 were more likely to be obese if they were ex-smokers, physical inactive, or lived in rural areas. Conclusion These findings highlight growing disparities in obesity within birth cohorts, underscoring the need for targeted health policies that promote smoking cessation and physical activity, especially in rural areas.

Background and Objectives: In previous studies, high homocysteine levels were associated with high cardiovascular mortality. However, these results were inconsistent with those of randomized controlled trials. We aimed to evaluate the causal role of homocysteine on allcause and cardiovascular mortality using Mendelian randomization (MR) analysis. Methods: This study included the 10,005 participants in the Namwon Study. In conventional observational analysis, age, sex, survey years, lifestyles, body mass index, comorbidities, and serum folate level were adjusted using multivariate Cox proportional regression. MR using 2-stage least squares regression was used to evaluate the association between genetically predicted plasma homocysteine levels and mortality. Age, sex, and survey years were adjusted for each stage. The methylenetetrahydrofolate reductase (MTHFR) polymorphism was used as an instrumental variable for predicting plasma homocysteine levels. Results: Observed homocysteine levels were positively associated with all-cause (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.26–1.54) and cardiovascular (HR, 1.62; 95% CI, 1.28–2.06) mortality when plasma homocysteine levels doubled. However, these associations were not significant in MR analysis. The HRs of doubling genetically predicted plasma homocysteine levels for all-cause and cardiovascular mortality were 0.99 (95% CI, 0.62–1.57) and 1.76 (95% CI, 0.54–5.77), respectively. Conclusions This MR analysis did not support a causal role for elevated plasma homocysteine concentrations in premature deaths.

OBJECTIVES: Elevated C-reactive protein (CRP) levels are associated with an increased risk for colorectal cancer (CRC), as well as a poor prognosis, but it remains unclear whether these associations are causal. This study examined the potential causality between CRP levels and CRC survival using 2-sample Mendelian randomization (MR). METHODS: From the Korean Genome and Epidemiology Study, a genome-wide association study (n=59,605), 7 single-nucleotide polymorphisms (SNPs) related to log2-transformed CRP levels were extracted as instrumental variables for CRP levels. The associations between the genetically predicted CRP and CRC-specific and overall mortality among CRC patients (n=6,460) were evaluated by Aalen’s additive hazard model. The sensitivity analysis excluded a SNP related to the blood lipid profile. RESULTS: During a median of 8.5 years of follow-up, among 6,460 CRC patients, 2,676 (41.4%) CRC patients died from all causes and 1,622 (25.1%) died from CRC. Genetically predicted CRP levels were not significantly associated with overall or CRC-specific mortality in CRC patients. The hazard difference per 1,000 person-years for overall and CRC-specific mortality per 2-fold increase in CRP levels was -2.92 (95% confidence interval [CI], -14.05 to 8.21) and -0.76 (95% CI, -9.61 to 8.08), respectively. These associations were consistent in a subgroup analysis according to metastasis and a sensitivity analysis excluding possible pleiotropic SNPs. CONCLUSIONS Our findings do not support a causal role for genetically predisposed CRP levels in CRC survival.

Purpose: In this prospective study, we evaluated the association between the serum levels of antioxidants uric acid (UA), albumin, and total bilirubin and the risk of cancer in a Korean population. Materials and Methods: A total of 15882 subjects were followed up for cancer development and cancer-related death. During the follow-up period, 1619 cancer diagnoses and 617 cancer-related deaths were recorded. Cox proportional regression was performed to calculate the hazard ratio (HR) per standard deviation (SD) increment and 95% confidence interval (CI). The model was adjusted for covariates such as the age, sex, smoking, alcohol consumption, physical activity, education level, body mass index, and family history. Sensitivity analyses using the study subjects with physiological serum levels of each indicator were also performed. Results: UA levels were positively correlated with cancer risk (HR per SD increment 1.04; 95% CI, 1.01–1.09), and albumin levels were inversely associated with the overall cancer risk (HR, 0.92; 95% CI, 0.88–0.96) and cancer-related death (HR, 0.86; 95% CI, 0.80–0.93). Total bilirubin levels were negatively correlated with the risk of cancer-related death (HR, 0.91; 95% CI, 0.83–0.99). By cancer type, UA was positively associated with prostate cancer, total bilirubin was positively associated with liver cancer, and albumin was inversely associated with lung cancer. Conclusion The findings of this study support the role of antioxidants in carcinogenesis. Future large-cohort studies are needed to confirm the predictive value of albumin, UA, and total bilirubin levels in each type of cancer.

Purpose: In this prospective study, we evaluated the association between the serum levels of antioxidants uric acid (UA), albumin, and total bilirubin and the risk of cancer in a Korean population. Materials and Methods: A total of 15882 subjects were followed up for cancer development and cancer-related death. During the follow-up period, 1619 cancer diagnoses and 617 cancer-related deaths were recorded. Cox proportional regression was performed to calculate the hazard ratio (HR) per standard deviation (SD) increment and 95% confidence interval (CI). The model was adjusted for covariates such as the age, sex, smoking, alcohol consumption, physical activity, education level, body mass index, and family history. Sensitivity analyses using the study subjects with physiological serum levels of each indicator were also performed. Results: UA levels were positively correlated with cancer risk (HR per SD increment 1.04; 95% CI, 1.01–1.09), and albumin levels were inversely associated with the overall cancer risk (HR, 0.92; 95% CI, 0.88–0.96) and cancer-related death (HR, 0.86; 95% CI, 0.80–0.93). Total bilirubin levels were negatively correlated with the risk of cancer-related death (HR, 0.91; 95% CI, 0.83–0.99). By cancer type, UA was positively associated with prostate cancer, total bilirubin was positively associated with liver cancer, and albumin was inversely associated with lung cancer. Conclusion The findings of this study support the role of antioxidants in carcinogenesis. Future large-cohort studies are needed to confirm the predictive value of albumin, UA, and total bilirubin levels in each type of cancer.

Purpose: Excessive alcohol consumption has been linked to an increased risk of colorectal cancer (CRC). We evaluated the association between alcohol-related genetic variants and CRC risk. Materials and Methods: The study cohort consisted of 5,435 CRC cases and 3,553 population-based cancer-free controls. Genotype data were generated from germline DNA using the Infinium OncoArray-500K BeadChip in 2,535 cases and 2,287 controls and the Infinium Multi-Ethnic Global BeadChip in 2,900 cases and 1,266 controls. The associations between aldehyde dehydrogenase 2 (ALDH2) rs671 and alcohol dehydrogenase 1B (ADH1B) rs1229984 polymorphisms and CRC risk were assessed using multivariate logistic regression analyses. Results: Compared with the major homozygous ALDH2 genotype (GG), heterozygous or minor homozygous ALDH2 genotype (GA or AA, related to a low alcohol consumption) was significantly associated with a reduced risk for CRC in men (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.68 to 0.90), but not in women (OR, 0.70; 95% CI, 0.47 to 1.05). A stronger association was found among regular drinkers (OR, 0.58; 95% CI, 0.47 to 0.71 in men and OR, 0.33; 95% CI, 0.18 to 0.58 in women). No association of CRC risk with ADH1B rs1229984 genotype was found. The association between alcohol-related combined genotypes and risk of CRC was significant (p for linear=0.001). The combined genotype with the highest genetically predicted alcohol consumption (ALDH2 rs671 GG and ADH1B rs1229984 AG/GG) was associated with a high risk for CRC (OR, 1.35; 95% CI, 1.11 to 1.63). Conclusion Our study provides strong evidence for a possible causal association between alcohol consumption and CRC risk.

Purpose: Excessive alcohol consumption has been linked to an increased risk of colorectal cancer (CRC). We evaluated the association between alcohol-related genetic variants and CRC risk. Materials and Methods: The study cohort consisted of 5,435 CRC cases and 3,553 population-based cancer-free controls. Genotype data were generated from germline DNA using the Infinium OncoArray-500K BeadChip in 2,535 cases and 2,287 controls and the Infinium Multi-Ethnic Global BeadChip in 2,900 cases and 1,266 controls. The associations between aldehyde dehydrogenase 2 (ALDH2) rs671 and alcohol dehydrogenase 1B (ADH1B) rs1229984 polymorphisms and CRC risk were assessed using multivariate logistic regression analyses. Results: Compared with the major homozygous ALDH2 genotype (GG), heterozygous or minor homozygous ALDH2 genotype (GA or AA, related to a low alcohol consumption) was significantly associated with a reduced risk for CRC in men (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.68 to 0.90), but not in women (OR, 0.70; 95% CI, 0.47 to 1.05). A stronger association was found among regular drinkers (OR, 0.58; 95% CI, 0.47 to 0.71 in men and OR, 0.33; 95% CI, 0.18 to 0.58 in women). No association of CRC risk with ADH1B rs1229984 genotype was found. The association between alcohol-related combined genotypes and risk of CRC was significant (p for linear=0.001). The combined genotype with the highest genetically predicted alcohol consumption (ALDH2 rs671 GG and ADH1B rs1229984 AG/GG) was associated with a high risk for CRC (OR, 1.35; 95% CI, 1.11 to 1.63). Conclusion Our study provides strong evidence for a possible causal association between alcohol consumption and CRC risk.

BACKGROUND: Elevated blood pressure is a major preventable cause of cardiovascular diseases. Alcohol consumption is a well-known risk factor of elevated blood pressure. The aldehyde dehydrogenase 2 (ALDH2) polymorphism is common in Eastern Asians, and inactive ALDH2 genotypes are associated with both avoiding alcohol consumption and aldehyde accumulation. Therefore, this study assessed the associations between alcohol consumption and hypertension and blood pressure according to the ALDH2 genotypes.METHODS: This study consists of 8,526 participants in the Dong-gu Study. Multivariate logistic regression was used to calculate the odds ratio (OR) according to alcohol consumption after stratifying by gender and ALDH2 genotypes. Multivariate linear regression was performed to estimate the systolic blood pressure (SBP) and diastolic blood pressure (DBP) according to the amount of alcohol consumed.RESULTS: In men, alcohol consumption was positively associated with both SBP and DBP in active ALDH2 carriers, but not in inactive ALDH2 carriers. In active ALDH2 carriers, compared to non-drinkers, the OR of hypertension was 1.16 (95% confidence interval [CI], 0.91–1.49) for < 1 drink/day, and 1.44 (95% CI, 1.15–1.80) for ≥ 1 drink/day in men. With each 1 drink/day increase, SBP and DBP increased by 3 and 1 mmHg in men, respectively. There was no significant association between ALDH2 genotypes and hypertension and blood pressure in women.CONCLUSION: ALDH2 genotype modified the association between alcohol consumption and blood pressure in men. There was a positive relationship between alcohol consumption and blood pressure in active ALDH2 carriers, but no significant relationship in inactive ALDH2 carriers.
Acetaldehyde ; Alcohol Drinking ; Aldehyde Dehydrogenase ; Asian Continental Ancestry Group ; Blood Pressure ; Cardiovascular Diseases ; Cohort Studies ; Female ; Genotype ; Humans ; Hypertension ; Linear Models ; Logistic Models ; Male ; Odds Ratio ; Oxidoreductases ; Risk Factors

The association between alcohol and gastric cancer is stronger in East Asians than in other ethnic groups, presumably due to an aldehyde dehydrogenase 2 (ALDH2) polymorphism. Therefore, we investigated the relationship between the ALDH2 rs671 polymorphism and gastric cancer in a Korean population. This case-control study included 3,245 hospital patients newly diagnosed with gastric cancer and 8,732 population controls. The ALDH2 rs671 genotype was classified as inactive ALDH2 (GG) or active ALDH2 (GA/AA). The risk of gastric cancer was higher in men with the inactive ALDH2 than in those with active ALDH2 (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.09–1.39), whereas no significant association was found between ALDH2 genotype and gastric cancer in women (OR, 1.00; 95% CI, 0.99–1.02). In men, the association between ALDH2 genotype and gastric cancer was stronger in current drinkers. Our findings support the previously reported association between inactive ALDH2 and high risk of gastric cancer.

BACKGROUND: Elevated blood pressure is a major preventable cause of cardiovascular diseases. Alcohol consumption is a well-known risk factor of elevated blood pressure. The aldehyde dehydrogenase 2 (ALDH2) polymorphism is common in Eastern Asians, and inactive ALDH2 genotypes are associated with both avoiding alcohol consumption and aldehyde accumulation. Therefore, this study assessed the associations between alcohol consumption and hypertension and blood pressure according to the ALDH2 genotypes. METHODS: This study consists of 8,526 participants in the Dong-gu Study. Multivariate logistic regression was used to calculate the odds ratio (OR) according to alcohol consumption after stratifying by gender and ALDH2 genotypes. Multivariate linear regression was performed to estimate the systolic blood pressure (SBP) and diastolic blood pressure (DBP) according to the amount of alcohol consumed. RESULTS: In men, alcohol consumption was positively associated with both SBP and DBP in active ALDH2 carriers, but not in inactive ALDH2 carriers. In active ALDH2 carriers, compared to non-drinkers, the OR of hypertension was 1.16 (95% confidence interval [CI], 0.91–1.49) for < 1 drink/day, and 1.44 (95% CI, 1.15–1.80) for ≥ 1 drink/day in men. With each 1 drink/day increase, SBP and DBP increased by 3 and 1 mmHg in men, respectively. There was no significant association between ALDH2 genotypes and hypertension and blood pressure in women. CONCLUSION ALDH2 genotype modified the association between alcohol consumption and blood pressure in men. There was a positive relationship between alcohol consumption and blood pressure in active ALDH2 carriers, but no significant relationship in inactive ALDH2 carriers.