Sex and Economic Disparity Related to Reperfusion Therapies for Patients with Acute Ischemic Stroke in South Korea across a 10-Year Period: A Nationwide Population-Based Study Using the National Health Insurance Database.

A complete enumeration study was conducted to evaluate trends related to reperfusion therapies (intravenous thrombolysis (IVT) and endovascular treatment (EVT)) in acute ischemic stroke (AIS) in South Korea, according to sex, economic status, and age, over a 10-year period retrospectively, using the National Health Information Database (NHIS-2020-1-481). This study included AIS patients aged ≥20 years who were hospitalized in a general hospital or tertiary hospital for ≥4 days and underwent brain imaging during the same period. Study participants were classified by sex, economic status (Medical Aid beneficiaries and National Health Insurance beneficiaries) and age (20-44, 45-64, 65-79, and ≥80 years). Women showed a significantly lower OR (Odds ratio) than men in IVT (OR: 0.75; 95% CI: 0.73-0.77), EVT (OR: 0.96; 95% CI: 0.93-0.99), and any therapy (OR: 0.82; 95% CI: 0.80-0.84). The Medical Aid beneficiaries showed significantly lower OR in IVT (OR 0.91, 95% CI 0.88-0.95), EVT (OR 0.93, 95% CI 0.89-0.98), and either therapy (OR 0.92, 95% CI 0.90-0.95) than the National Health Insurance beneficiaries. This study showed sex and economic disparity related to reperfusion therapies in patients with AIS in Korea.

Association of coffee drinking with all-cause and cause-specific mortality in over 190,000 individuals: data from two prospective studies.

We examined the association of coffee drinking with all-cause and cause-specific mortality in a pooled analysis of two Korean prospective cohort studies: The Korea National Health and Nutrition Examination Survey and the Korean Genome and Epidemiology Study. We included 192,222 participants, and a total of 6057 deaths were documented. Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs), and the HRs were combined using a random-effects model. Coffee drinking was associated with a lower risk of all-cause mortality [HR (95% CI) = 0.84 (0.77-0.92), for ≥3 cups/day of coffee drinking versus non-drinkers; p for trend = 0.004]. We observed the potential benefit of coffee drinking for mortality due to cardiovascular disease, respiratory disease, and diabetes, but not for cancer mortality. Overall, we found that moderate coffee drinking was associated with a lower risk of death in population-based cohort analysis of Korean adults.

The Association between Plasma Concentration of Phytoestrogens and Hypertension within the Korean Multicenter Cancer Cohort.

In order to examine the association between plasma phytoestrogen concentration (genistein, daidzein, equol and enterolactone) and hypertension, we conducted a nested case-control study for 229 hypertension cases including 112 prehypertension and 159 healthy controls derived from the Korean Multi-center Cancer Cohort (KMCC). The concentration of plasma phytoestrogens was measured using time-resolved fluoroimmunoassay. We assessed the association between plasma phytoestrogens and hypertension using logistic regression models using odds ratio (OR) and 95% confidence interval (95%CI). The highest tertile of plasma equol and enterolactone concentration exhibited a significantly decreased risk of hypertension (equol, OR = 0.34, 95%CI 0.20-0.57; enterolactone, OR = 0.32, 95%CI 0.18-0.57), compared with the lowest tertile. Equol and enterolactone showed reduced ORs for prehypertension (the highest tertile relative to the lowest tertile, OR = 0.50, 95%CI 0.26-0.96; OR = 0.38, 95%CI 0.19-0.75, respectively) and hypertension (OR = 0.42, 95%CI 0.22-0.81; OR = 0.28, 95%CI 0.14-0.54, respectively). There was a stronger association in hypertension (the highest tertile relative to the lowest tertile in obesity vs. non-obesity; equol, OR = 0.06 vs. 0.63; enterolactone, OR = 0.07 vs. 0.46; both p-heterogeneity < 0.01). This study suggests that equol and enterolactone may contribute to prevent primarily prehypertension and hypertension, and control cardiovascular disease (CVD) based on the continuum of hypertension and CVD. Further study to assess hypertension risk based on useful biomarkers, including phytoestrogens, may contribute to primary prevention of hypertension.

The Effect of Korean Red Ginseng on Symptoms and Inflammation in Patients With Allergic Rhinitis.

Korean red ginseng (KRG) has been traditionally used in Korea for health improvement. However, the clinical effect of KRG intake on the symptoms in patients with allergic rhinitis remains unknown. Our study was performed to identify the clinical effects of KRG on patients with allergic rhinitis and to examine the effect of KRG on allergic inflammatory reaction. We evaluated 60 patients with allergic rhinitis. All the patients were treated for 4 weeks. The patients were divided into 3 groups, according to the medication. Twenty patients were treated with KRG, 20 patients with the placebo, and 20 patients with the antihistamine. The patients recorded their symptoms in a daily symptom diary card. The patients checked the peak nasal inspiratory flow rate 2 times a day. Total serum immunoglobulin E (IgE) and serum-specific IgE were measured by ImmunoCap method before and after 4-week medication. The Th2 cytokines interleukin-4 (IL-4), IL-5, and IL-10 were checked in the serum before and after the 4-week treatment. The eosinophil counts in the nasal smears were checked. Korean red ginseng group has shown the significant improvement in rhinorrhea, nasal itching, and eye itching. Both the antihistamine and KRG groups showed a significant decrease in total IgE level at the end of treatment. The serum IL-4 level and eosinophil counts in the nasal smears were significantly decreased both in the antihistamine and in the KRG groups. In conclusion, KRG might be a useful treatment modality for patients with allergic rhinitis.

Low white-matter integrity between the left thalamus and inferior frontal gyrus in patients with insomnia disorder

Background: Previous studies have reported functional and structural abnormalities in the thalamus and the pars triangularis of the inferior frontal gyrus in patients with insomnia disorder. However, no studies have been conducted on the white-matter tracts between these 2 brain regions. We aimed to compare the white-matter integrity and structure of the left thalamus­pars triangularis tracts between patients with insomnia and controls, and to characterize the relationship between white-matter integrity and clinical features in patients with insomnia. Methods: In total, 22 participants with insomnia disorder and 27 controls underwent overnight polysomnography and brain magnetic resonance imaging, and then completed self-report clinical questionnaires and neurocognitive tests for spatial planning. Structural and diffusion measures such as fractional anisotropy, axial diffusivity, radial diffusivity and trace were analyzed in group comparison and correlation analyses. Results: The insomnia group showed significantly lower fractional anisotropy (F = 8.647, p = 0.02) and axial diffusivity (F = 5.895, p = 0.038) in the left thalamus­pars triangularis tracts than controls. In patients with insomnia, fractional anisotropy in the tracts was correlated with the results of the Stockings of Cambridge test (r = 0.451, p = 0.034), and radial diffusivity was correlated with Epworth Sleepiness Scale score (r = 0.437, p = 0.042). Limitations: Limitations included analyses of limited brain regions and the cross-sectional design. Conclusion: The insomnia group showed decreased integrity in the left thalamus­pars triangularis tracts, and integrity was correlated with cognition and daytime sleepiness. These results may imply that insomnia is characterized by disintegration of the white-matter tract between the left thalamus and inferior frontal gyrus.

Plasma phytoestrogens concentration and risk of colorectal cancer in two different Asian populations.

BACKGROUND & AIMS: To evaluate the relationship between phytoestrogen and colon cancer risk, we quantified plasma isoflavones (Genistein and Daidzein) and lignan (enterolactone) in a Korean nested case-control study and conducted replication study in a Vietnamese case-control study. METHODS: Study populations of 101 cases and 391 controls were selected from the Korean Multicenter Cancer Cohort which was constructed from 1993 to 2004. For replication study, Vietnamese hospital-based case-control subjects of 222 cases and 206 controls were selected from 2003 to 2007. The concentrations of plasma genistein, daidzein, and enterolactone were quantified by liquid chromatography-mass spectrometry. Logistic regression models were used to compute odds ratios (ORs) and 95% confidence intervals (CIs), and meta-analysis was conducted to estimate combined ORs (CORs) and 95% Cis of Korean and Vietnamese population in 2014. RESULTS: Genistein showed a continual decrease in colorectal cancer risk according to level up of the concentration categories in Korean and Vietnamese population (P for trend = 0.032, and 0.001, respectively) and a significantly decreased risk was found at the highest concentration of genistein and daidzein (for the highest category compared to the lowest: COR (95% CI) = 0.46 (0.30-0.69), and COR (95% CI) = 0.54 (0.36-0.82)). When the study population was stratified, the beneficial relationship of genistein with colorectal cancer was observed regardless of sex and anatomical subtype. However, enterolacton level was not associated with colorectal cancer risk. CONCLUSIONS: High plasma levels of isoflavones had relationship with a decreased risk of colorectal cancer, regardless of different ethnic background.

Gene polymorphisms in the ornithine decarboxylase-polyamine pathway modify gastric cancer risk by interaction with isoflavone concentrations.

BACKGROUND: The study aimed to examine the association between genes encoding molecules in the ornithine decarboxylase (ODC)-polyamine pathway (ODC1, AMD1, NQO1, NOS2A, and OAZ2) and gastric cancer risk and whether the gene-phytoestrogen interaction modifies gastric cancer risk. METHODS: Among 76 gastric cancer cases and their 1:4 matched controls within the Korean Multi-center Cancer Cohort, a total of 30 SNPs in five genes involved in the ODC pathway were primarily analyzed. The second-stage genotyping in 388 matched case-control sets was conducted to reevaluate the significant SNPs interacting with phytoestrogens during the primary analysis. The summary odds ratios (ORs) [95 % confidence intervals (CIs)] for gastric cancer were estimated. Interaction effects between the SNPs and plasma concentrations of phytoestrogens (genistein, daidzein, equol, and enterolactone) were evaluated. RESULTS: In the pooled analysis, NQO1 rs1800566 showed significant genetic effects on gastric cancer without heterogeneity [OR 0.83 (95 % CI 0.70-0.995)] and a greater decreased risk at high genistein/daidzein levels [OR 0.36 (95 % CI 0.15-0.90) and OR 0.26 (95 % CI 0.10-0.64), respectively; p interaction < 0.05]. Risk alleles of AMD1 rs1279599, AMD1 rs7768897, and OAZ2 rs7403751 had a significant gene-phytoestrogen (genistein and daidzein) interaction effect to modify the development of gastric cancer. They had an increased gastric cancer risk at low isoflavone levels, but a decreased risk at high isoflavone levels (p interaction < 0.01). CONCLUSIONS: Our findings suggest that common variants in the genes involved in the ODC pathway may contribute to the risk of gastric cancer possibly by modulating ODC polyamine biosynthesis or by interaction between isoflavones and NQO1, OAZ2, and AMD1.

Interaction effects between genes involved in the AKT signaling pathway and phytoestrogens in gastric carcinogenesis: a nested case-control study from the Korean Multi-Center Cancer Cohort.

SCOPE: To investigate whether genes involved in AKT/nuclear factor kappa B signaling and/or gene-environment interactions between the genes and phytoestrogens may be susceptible factors for gastric cancer. METHODS AND RESULTS: The representative single nucleotide polymorphisms (SNPs) identified during the primary analysis (screening a total of 622 SNPs within ± 5 kbp of the 51 target gene locations) were further investigated in 317 matched case-control sets. The summary odds ratios (ORs) and 95% confidence intervals (CIs) for gastric cancer were calculated. Interaction effects between the SNPs and phytoestrogen biomarkers (genistein, daidzein, equol, and enterolactone) were computed. CDK1 rs4145643, FAS rs6586161, and FAS rs1468063 in the AKT signaling pathway presented significant genetic effects on gastric cancer (OR = 0.81 (95% CI: 0.66-0.99) for CDK1 rs4145643; OR = 1.27 (95% CI: 1.03-1.58) for FAS rs6586161; OR = 1.29 (95% CI: 1.03-1.56) for FAS rs1468063; Cochran Q statistics > 0.10). Risk alleles of FAS rs6586161, FAS rs1468063, MAP3K1 rs16886448, and MAP3K1 rs252902 showed significant interaction effects with enterolactone (p(interaction) < 0.05). CONCLUSION: CDK1 and FAS genes involved in AKT signaling and influenced by anti-carcinogenic property of phytoestrogens can play a role as susceptible genetic factors in gastric carcinogenesis. FAS and MAP3K1 genes significantly interact with enterolactone, thereby modifying the individual's risk for gastric cancer.

Genetic susceptibility on CagA-interacting molecules and gene-environment interaction with phytoestrogens: a putative risk factor for gastric cancer.

OBJECTIVES: To evaluate whether genes that encode CagA-interacting molecules (SRC, PTPN11, CRK, CRKL, CSK, c-MET and GRB2) are associated with gastric cancer risk and whether an interaction between these genes and phytoestrogens modify gastric cancer risk. METHODS: In the discovery phase, 137 candidate SNPs in seven genes were analyzed in 76 incident gastric cancer cases and 322 matched controls from the Korean Multi-Center Cancer Cohort. Five significant SNPs in three genes (SRC, c-MET and CRK) were re-evaluated in 386 cases and 348 controls in the extension phase. Odds ratios (ORs) for gastric cancer risk were estimated adjusted for age, smoking, H. pylori seropositivity and CagA strain positivity. Summarized ORs in the total study population (462 cases and 670 controls) were presented using pooled- and meta-analysis. Plasma concentrations of phytoestrogens (genistein, daidzein, equol and enterolactone) were measured using the time-resolved fluoroimmunoassay. RESULTS: SRC rs6122566, rs6124914, c-MET rs41739, and CRK rs7208768 showed significant genetic effects for gastric cancer in both the pooled and meta-analysis without heterogeneity (pooled OR = 3.96 [95% CI 2.05-7.65], 1.24 [95% CI = 1.01-1.53], 1.19 [95% CI = 1.01-1.41], and 1.37 [95% CI = 1.15-1.62], respectively; meta OR = 4.59 [95% CI 2.74-7.70], 1.36 [95% CI = 1.09-1.70], 1.20 [95% CI = 1.00-1.44], and 1.32 [95% CI = 1.10-1.57], respectively). Risk allele of CRK rs7208768 had a significantly increased risk for gastric cancer at low phytoestrogen levels (p interaction<0.05). CONCLUSIONS: Our findings suggest that SRC, c-MET and CRK play a key role in gastric carcinogenesis by modulating CagA signal transductions and interaction between CRK gene and phytoestrogens modify gastric cancer risk.

Isoflavones from phytoestrogens and gastric cancer risk: a nested case-control study within the Korean Multicenter Cancer Cohort.

BACKGROUND: The role of soybean products in gastric cancer risk is not clear in epidemiologic studies due to measurement error from dietary intake questionnaires and due to different degrees of bias according to study design. To examine the association between soybean products and gastric cancer risk, we measured phytoestrogen biological markers in a nested case-control study. METHODS: The study population was composed of 131 cases and 393 matched controls within the Korean Multicenter Cancer Cohort. The concentrations of the four biomarkers in the plasma samples were measured using time-resolved fluoroimmunoassay. Conditional and unconditional logistic regression models were used to compute the odds ratio (OR) and 95% confidence intervals (CI). RESULTS: Median plasma concentrations of genistein (229 nmol/L for controls, 181.8 nmol/L for cases; P=0.07) and daidzein (131.2 nmol/L for controls, 80.5 nmol/L for cases; P=0.04) in cases were lower than in controls, whereas equol concentrations were similar. Compared with the reference group, gastric cancer risk decreased in the highest groups for genistein (OR, 0.54; 95% CI, 0.31-0.93) and daidzein (OR, 0.21; 95% CI, 0.08-0.58). Higher equol concentrations were associated with a decreased risk for gastric cancer (OR, 0.50; 95% CI, 0.27-0.90). The combination of the highest concentrations for each isoflavone category was associated with a 0.09-fold decreased risk for gastric cancer compared with the combination of the lowest concentrations for each category. There was no association between plasma lignan concentrations and gastric cancer. CONCLUSIONS: High serum concentrations of isoflavones were associated with a decreased risk for gastric cancer. IMPACT: These results suggest a beneficial effect of high soybean product intake for gastric cancer risk.

Soybean product intake modifies the association between interleukin-10 genetic polymorphisms and gastric cancer risk.

In this study, our aim was to investigate the association of inflammation-related genetic polymorphisms and gastric cancer risk and to examine whether the combined effect of soybean product intake modified cancer risk. Eighty-four incident gastric cancer cases and 336 matched controls were selected from the Korean Multi-Center Cancer Cohort. We selected 14 single nucleotide polymorphisms (SNP) from 5 genes [interleukin (IL)-1beta, IL-2, IL-4, IL-8, and IL-10] and used unconditional logistic regression model to calculate the odds ratios (OR) and 95% CI adjusting for H. pylori seropositivity, smoking, age, sex, enrollment year, and residential area. The risk for gastric cancer in relation to genetic polymorphisms and haplotypes were assessed according to soybean product intake levels. Although no single SNP effect was found, the combined effect between IL-10 gene variants of -592 GG/GA, -819 TC/CC, or -1082 AG/GG and low intake of soybean products had an increased risk for gastric cancer compared with the group with no risk gene variants and a high intake of soybean products (OR [95% CI] = 2.82 [1.04-7.62], 2.75 [1.02-7.44], and 4.34 [1.51-12.5], respectively). Among the low-soybean product intake group, IL-10 CCG haplotype had an increased risk of gastric cancer (OR = 3.38 [1.40-8.13]) relative to the ATA haplotype. Our results suggest that the association between IL-10 genetic polymorphisms and gastric cancer risk was modified by soybean product intake.