Keum Ji Jung

Body-mass index and all-cause mortality: Individual-participant-data meta-analysis of 239 prospective studies in four continents.

Summary Background Overweight and obesity are increasing worldwide. To help assess their relevance to mortality in different populations we conducted individual-participant data meta-analyses of prospective studies of body-mass index (BMI), limiting confounding and reverse causality by restricting analyses to never-smokers and excluding pre-existing disease and the first 5 years of follow-up. Methods Of 10 625 411 participants in Asia, Australia and New Zealand, Europe, and North America from 239 prospective studies (median follow-up 13·7 years, IQR 11·4–14·7), 3 951 455 people in 189 studies were never-smokers without chronic diseases at recruitment who survived 5 years, of whom 385 879 died. The primary analyses are of these deaths, and study, age, and sex adjusted hazard ratios (HRs), relative to BMI 22·5–<25·0 kg/m2. Findings All-cause mortality was minimal at 20·0–25·0 kg/m2 (HR 1·00, 95% CI 0·98–1·02 for BMI 20·0–<22·5 kg/m2; 1·00, 0·99–1·01 for BMI 22·5–<25·0 kg/m2), and increased significantly both just below this range (1·13, 1·09–1·17 for BMI 18·5–<20·0 kg/m2; 1·51, 1·43–1·59 for BMI 15·0–<18·5) and throughout the overweight range (1·07, 1·07–1·08 for BMI 25·0–<27·5 kg/m2; 1·20, 1·18–1·22 for BMI 27·5–<30·0 kg/m2). The HR for obesity grade 1 (BMI 30·0–<35·0 kg/m2) was 1·45, 95% CI 1·41–1·48; the HR for obesity grade 2 (35·0–<40·0 kg/m2) was 1·94, 1·87–2·01; and the HR for obesity grade 3 (40·0–<60·0 kg/m2) was 2·76, 2·60–2·92. For BMI over 25·0 kg/m2, mortality increased approximately log-linearly with BMI; the HR per 5 kg/m2 units higher BMI was 1·39 (1·34–1·43) in Europe, 1·29 (1·26–1·32) in North America, 1·39 (1·34–1·44) in east Asia, and 1·31 (1·27–1·35) in Australia and New Zealand. This HR per 5 kg/m2 units higher BMI (for BMI over 25 kg/m2) was greater in younger than older people (1·52, 95% CI 1·47–1·56, for BMI measured at 35–49 years vs 1·21, 1·17–1·25, for BMI measured at 70–89 years; pheterogeneity<0·0001), greater in men than women (1·51, 1·46–1·56, vs 1·30, 1·26–1·33; pheterogeneity<0·0001), but similar in studies with self-reported and measured BMI. Interpretation The associations of both overweight and obesity with higher all-cause mortality were broadly consistent in four continents. This finding supports strategies to combat the entire spectrum of excess adiposity in many populations. Funding UK Medical Research Council, British Heart Foundation, National Institute for Health Research, US National Institutes of Health.

A coronary heart disease prediction model: the Korean Heart Study

Objective The objectives of this study were to develop a coronary heart disease (CHD) risk model among the Korean Heart Study (KHS) population and compare it with the Framingham CHD risk score. Design A prospective cohort study within a national insurance system. Setting 18 health promotion centres nationwide between 1996 and 2001 in Korea. Participants 268 315 Koreans between the ages of 30 and 74 years without CHD at baseline. Outcome measure Non-fatal or fatal CHD events between 1997 and 2011. During an 11.6-year median follow-up, 2596 CHD events (1903 non-fatal and 693 fatal) occurred in the cohort. The optimal CHD model was created by adding high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides to the basic CHD model, evaluating using the area under the receiver operating characteristic curve (ROC) and continuous net reclassification index (NRI). Results The optimal CHD models for men and women included HDL-cholesterol (NRI=0.284) and triglycerides (NRI=0.207) from the basic CHD model, respectively. The discrimination using the CHD model in the Korean cohort was high: the areas under ROC were 0.764 (95% CI 0.752 to 0.774) for men and 0.815 (95% CI 0.795 to 0.835) for women. The Framingham risk function predicted 3–6 times as many CHD events than observed. Recalibration of the Framingham function using the mean values of risk factors and mean CHD incidence rates of the KHS cohort substantially improved the performance of the Framingham functions in the KHS cohort. Conclusions The present study provides the first evidence that the Framingham risk function overestimates the risk of CHD in the Korean population where CHD incidence is low. The Korean CHD risk model is well-calculated alternations which can be used to predict an individuals risk of CHD and provides a useful guide to identify the groups at high risk for CHD among Koreans.

Genome-Wide Association Meta-analysis Identifies Novel Variants Associated With Fasting Plasma Glucose in East Asians

Fasting plasma glucose (FPG) has been recognized as an important indicator for the overall glycemic state preceding the onset of metabolic diseases. So far, most indentified genome-wide association loci for FPG were derived from populations with European ancestry, with a few exceptions. To extend a thorough catalog for FPG loci, we conducted meta-analyses of 13 genome-wide association studies in up to 24,740 nondiabetic subjects with East Asian ancestry. Follow-up replication analyses in up to an additional 21,345 participants identified three new FPG loci reaching genome-wide significance in or near PDK1-RAPGEF4, KANK1, and IGF1R. Our results could provide additional insight into the genetic variation implicated in fasting glucose regulation.

Genome-wide association studies in East Asians identify new loci for waist-hip ratio and waist circumference

Sixty genetic loci associated with abdominal obesity, measured by waist circumference (WC) and waist-hip ratio (WHR), have been previously identified, primarily from studies conducted in European-ancestry populations. We conducted a meta-analysis of associations of abdominal obesity with approximately 2.5 million single nucleotide polymorphisms (SNPs) among 53,052 (for WC) and 48,312 (for WHR) individuals of Asian descent, and replicated 33 selected SNPs among 3,762 to 17,110 additional individuals. We identified four novel loci near the EFEMP1, ADAMTSL3 , CNPY2, and GNAS genes that were associated with WC after adjustment for body mass index (BMI); two loci near the NID2 and HLA-DRB5 genes associated with WHR after adjustment for BMI, and three loci near the CEP120, TSC22D2, and SLC22A2 genes associated with WC without adjustment for BMI. Functional enrichment analyses revealed enrichment of corticotropin-releasing hormone signaling, GNRH signaling, and/or CDK5 signaling pathways for those newly-identified loci. Our study provides additional insight on genetic contribution to abdominal obesity.

Association between fasting serum glucose levels and incidence of colorectal cancer in Korean men: the Korean Cancer Prevention Study-II.

INTRODUCTION The incidence of colorectal cancer (CRC) is steadily increasing worldwide. Numerous studies have demonstrated that diabetes mellitus is related to an increased risk of CRC; however, the association between impaired fasting glucose and CRC is unclear. Therefore, we evaluated the correlation between fasting serum glucose (FSG) levels and the incidence of CRC, which can be used to develop novel methods for preventing CRC. METHODS A total of 175,677 individuals from the Korean Metabolic Syndrome Research Initiative study were enrolled between 2004 and 2011. The incidence of CRC was assessed during a mean follow-up of 4.7 years. Hazard ratios (HR) for CRC according to FSG levels were calculated with the Cox proportional hazard model adjusted for age, sex, body mass index, smoking status, alcohol consumption, and regular exercise. RESULTS The risk of developing CRC in subjects with high FSG was significant (HR, 1.45; 95% confidence interval [CI], 1.10-1.90), and the risk was higher in men (HR, 1.51; 95% CI, 1.12-2.05). The HR of rectal cancer, but not colon cancer, was significantly higher both in the total population and in men in the high FSG group. CONCLUSIONS The incidence of CRC positively correlated with FSG levels in men. Rectal cancer incidence was especially correlated with high FSG in the site-specific analysis. Therefore, serum glucose levels maybe a potential marker of colorectal cancer. Early detection and intervention for controlling elevated glucose levels may be indicated as a way to prevent carcinogenesis.

Age–period–cohort analysis of the suicide rate in Korea

BACKGROUND The suicide rate has been increasing in Korea, and the country now has the highest rank in the world. This study aimed to present the long-term trends in Koreas suicide rate using Joinpoint analysis and age-period-cohort (APC) modeling. METHODS The population and the number of suicides for each five-year age group were obtained from the National Statistical Office for the period 1984-2013 for Koreans aged 10 years and older. We determined the changes in the trends in age-standardized mortality rates using Joinpoint. APC modeling was performed to describe the trends in the suicide rate using the intrinsic estimator method. RESULTS The age-standardized suicide rate in men rapidly increased from 1989 to 2004, and slightly increased thereafter, whereas the suicide rate in women increased from 1989 to 2009 and then decreased thereafter. Within the same period, the suicide rate was higher among the older age groups than in the younger groups. Within the same birth cohort, the suicide rate of the older groups was also higher than that in the younger groups. Within the same age group, the suicide rate of the younger cohorts was higher than it was in the older cohorts. In the APC modeling, old age, recent period, and having been born before 1924 were associated with higher suicide rates. LIMITATIONS The accuracy and completeness of the suicide rate data may lead to bias. CONCLUSIONS This study showed an increasing trend in the suicide rates for men and women after 1989. These trends may be mainly attributed to cohort effects.

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

BackgroundGenome-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).ResultsSeven 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.ConclusionOur 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.

Bilirubin and Stroke Risk Using a Mendelian Randomization Design

Background and Purpose— Circulating bilirubin, a natural antioxidant, is associated with decreased risk of stroke. However, the nature of the relationship between the two remains unknown. We used a Mendelian randomization analysis to assess the causal effect of serum bilirubin on stroke risk in Koreans. Methods— The 14 single-nucleotide polymorphisms (SNPS) (<10–7) including rs6742078 of uridine diphosphoglucuronyl-transferase were selected from genome-wide association study of bilirubin level in the KCPS-II (Korean Cancer Prevention Study-II) Biobank subcohort consisting of 4793 healthy Korean and 806 stroke cases. Weighted genetic risk score was calculated using 14 SNPS selected from the top SNPS. Results— Both rs6742078 (F statistics=138) and weighted genetic risk score with 14 SNPS (F statistics=187) were strongly associated with bilirubin levels. Simultaneously, serum bilirubin level was associated with decreased risk of stroke in an ordinary least-squares analysis. However, in 2-stage least-squares Mendelian randomization analysis, no causal relationship between serum bilirubin and stroke risk was found. Conclusions— There is no evidence that bilirubin level is causally associated with risk of stroke in Koreans. Therefore, bilirubin level is not a risk determinant of stroke.

Depression as a risk factor for overall and hormone-related cancer: the Korean cancer prevention study.

Depression has been hypothesized to be a risk factor of cancer, especially hormone-related cancers. However, few studies have been conducted with large enough sample size and sufficient follow-up period to rigorously estimate these associations. We aim to examine the relationship between depression and risk of registry-documented overall and hormone-related cancers. In this 19 year prospective cohort study of general population, 601,775 Koreans aged 30-64 years had a biennial medical evaluation by the National Health Insurance Service in either 1992 or 1994. Major and minor depression was ascertained by a 9-item depression questionnaire. At baseline, major depression was identified in 7.4% and 10.2% and minor depression in 19.3% and 21.4% in men and women, respectively. During the follow-up, 49,744 cancers were identified in men and 7860 in women. Prostate cancer in men was positively related to minor depression (HR 1.13, 95% CI 1.05, 1.23), and cervical cancer in women was inversely related to major depression (HR 0.90, 95% CI 0.83, 0.98) after adjusting for potential confounders. Regarding overall cancer, major depression was positively related to overall cancer in men (HR 1.04, 95% CI 1.00, 1.08) and inversely related in women (HR 0.90, 95% CI 0.83, 0.98). There was no association between breast cancer and depression. Different direction and magnitude of association among gender and cancer subtypes suggest different psycho-behavioral and biological pathways in which depression may affect later cancer development. Further studies on the association of depression and cancer and the underlying mechanisms should be conducted on specific cancer subtypes.