Background: Neurogenic differentiation 1 (NeuroD1) is a representative small cell lung cancer (SCLC) transcription regulator involved in the carcinogenesis and behavior of SCLC.Histone modifications play an important role in transcription, and H3 lysine 4 trimethylation (H3K4me3) is primarily associated with promoter regions. Methods: We investigated the association between single nucleotide polymorphisms (SNPs) in NeuroD1 and H3K4me3 coincident regions, selected using ChIP sequencing (ChIP-seq), and the clinical outcomes of 261 patients with SCLC. Results: Among 230 SNPs, two were significantly associated with both the chemotherapy response and overall survival (OS) of patients with SCLC. RNF145 rs2043268A>G was associated with worse chemotherapy response and OS (under a recessive model, adjusted odds ratio [aOR], 0.50, 95% confidence interval [CI], 0.26–0.94, P = 0.031, and adjusted hazard ratio [aHR], 1.88, 95% CI, 1.38–2.57, P < 0.001). CINP rs762105A>G was also associated with worse chemotherapy response and OS (under a dominant model, aOR, 0.47, 95% CI, 0.23–0.99, P = 0.046, and aHR, 2.03, 95% CI, 1.47–2.82, P < 0.001). ChIP–quantitative polymerase chain reaction and luciferase assay confirmed that the two SNPs were located in the active promoter regions and influenced the promoter activity of each gene. Conclusion To summarize, among SNPs selected using ChIP-seq in promoter regions with high peaks in both NeuroD1 and H3K4me3, RNF145 rs2043268A>G and CINP rs762105A>G were associated with clinical outcomes in patients with SCLC and also affected the promoter activity of each gene.

Background: There has been no comparison of the determinants of admission route between acute ischemic stroke (AIS) and acute myocardial infarction (AMI). We examined whether factors associated with direct versus transferred-in admission to regional cardiocerebrovascular centers (RCVCs) differed between AIS and AMI. Methods: Using a nationwide RCVC registry, we identified consecutive patients presenting with AMI and AIS between July 2016 and December 2018. We explored factors associated with direct admission to RCVCs in patients with AIS and AMI and examined whether those associations differed between AIS and AMI, including interaction terms between each factor and disease type in multivariable models. To explore the influence of emergency medical service (EMS) paramedics on hospital selection, stratified analyses according to use of EMS were also performed. Results: Among the 17,897 and 8,927 AIS and AMI patients, 66.6% and 48.2% were directly admitted to RCVCs, respectively. Multivariable analysis showed that previous coronary heart disease, prehospital awareness, higher education level, and EMS use increased the odds of direct admission to RCVCs, but the odds ratio (OR) was different between AIS and AMI (for the first 3 factors, AMI > AIS; for EMS use, AMI < AIS). EMS use was the single most important factor for both AIS and AMI (OR, 4.72 vs. 3.90). Hypertension and hyperlipidemia increased, while living alone decreased the odds of direct admission only in AMI;additionally, age (65–74 years), previous stroke, and presentation during non-working hours increased the odds only in AIS. EMS use weakened the associations between direct admission and most factors in both AIS and AMI. Conclusions Various patient factors were differentially associated with direct admission to RCVCs between AIS and AMI. Public education for symptom awareness and use of EMS is essential in optimizing the transportation and hospitalization of patients with AMI and AIS.

Background/Aims: Genome wide and candidate gene association studies have identified polymorphisms associated with the risk of lung cancer in never-smokers. This study was conducted to evaluate the association between 11 polymorphisms identified in female never smokers and the lung cancer risk in male smokers. Methods: This study included 714 lung cancer patients and 626 healthy controls. The polymorphisms were genotyped using SEQUENOM MassARRAY iPLEX assay or Taq-Man assay. Results: Two polymorphisms were associated with the risk of lung cancer in male smokers, as in female never smokers. Male smokers carrying the rs4975616 variant allele had a significantly decreased risk of lung cancer (in a codominant model: odds ratio, 0.77; 95% confidence interval, 0.61 to 0.96; p = 0.02). The rs9387478 polymorphism also reduced lung cancer risk in male smokers (in a codominant model: odds ratio, 0.85; 95% confidence interval, 0.73 to 0.997; p = 0.046). In a stratified analysis, the association between these polymorphisms and the risk of lung cancer was predominant in lighter smokers and for cases of adenocarcinoma. Conclusions These results suggest that a subset of polymorphisms known to be associated with the risk of lung cancer in female never smokers is also associated with the risk of lung cancer in male smokers.

Purpose: To identify the clinical usefulness of serum M protein and to establish a rationale for regular follow-up with serum protein electrophoresis in solitary plasmacytoma. Materials and Methods: Sixty-nine patients with solitary plasmacytoma and solitary plasmacytoma with minimal marrow involvement according to the International Myeloma Working Group criteria were retrospectively reviewed. Results: At a median follow-up of 6.2 years, 5-year local control (LC), 5-year multiple myeloma-free survival (MMFS), 5-year failure-free survival (FFS), and 5-year overall survival (OS) were 82.6%, 44.1%, 41.8%, and 85.1%, respectively. Among the patients whose initial serum M protein was present or not evaluated, 37.3% of patients showed disappearance of serum M protein after various treatment. MMFS of these patients were comparable to non-secretory plasmacytoma with undetectable levels of M protein, and significantly better than patients with persistent M protein. Increase of serum M protein ≥0.1 g/dL was most predictive of treatment failure with area under the curve of 0.731. Conclusion Patients who eventually showed persistence of serum M protein after treatment showed worse MMFS and FFS compared to those whose serum M protein disappeared or who had initially non-secretory disease. The increase of serum M protein level ≥0.1 g/dL from current nadir was predictive of treatment failure. Therefore, regular follow-up with serum M protein is highly recommended especially unless the patient had initially non-secretory disease.

PURPOSE: Generally, aspirin is used as a protective agent against thrombogenic phenomenon after pulmonary valve replacement (PVR) using a bioprosthetic valve. However, the appropriate duration of aspirin use is unclear. We analyzed the impact of postoperative duration of aspirin use on the longevity of bioprosthetic pulmonary valves in patients who underwent repair for congenital heart diseases. METHODS: We retrospectively reviewed the clinical data of 137 patients who underwent PVR using a bioprosthetic valve between January 2000 and December 2003. Among these patients, 89 were included in our study and divided into groups I (≤12 months) and II (>12 months) according to duration of aspirin use. We analyzed echocardiographic data from 9 to 11 years after PVR. Pulmonary vale stenosis and regurgitation were classified as mild, moderate, or severe. RESULTS: The 89 patients consisted of 53 males and 36 females. Their mean age was 14.3±8.9 years (range, 2.6–48 years) and body weight was 37.6±14.7 kg (range, 14–72 kg). The postoperative duration of aspirin use was 7.3±2.9 months in group I and 32.8±28.4 months in group II. However, no significant difference in sex ratio, age, body weight, type of bioprosthetic valve, and number of early redo-PVRs. In the comparison of echocardiographic data about 10 years later, no significant difference in pulmonary valve function was found. The overall freedom rate from redo-PVR at 10 years showed no significant difference (P=0.498). CONCLUSION: Our results indicated no benefit from long-term aspirin medication (>6 months) in patients who underwent PVR with a bioprosthetic valve.
Aspirin* ; Body Weight ; Constriction, Pathologic ; Echocardiography ; Female ; Freedom ; Heart Defects, Congenital* ; Heart Diseases ; Humans ; Longevity* ; Male ; Pulmonary Valve* ; Retrospective Studies ; Sex Ratio

Recently, genetic variants in the WNT signaling pathway have been reported to affect the survival outcome of Caucasian patients with early stage non-small cell lung cancer (NSCLC). We therefore attempted to determine whether these same WNT signaling pathway gene variants had similar impacts on the survival outcome of NSCLC patients in a Korean population. A total of 761 patients with stages I-IIIA NSCLC were enrolled in this study. Eight variants of WNT pathway genes were genotyped and their association with overall survival and disease-free survival were analyzed. None of the eight variants were significantly associated with overall survival or disease-free survival. There were no differences in survival outcome after stratifying the subjects according to age, gender, smoking status, and histological type. These results suggest that genetic variants in the WNT signaling pathway may not affect the survival outcome of NSCLC in a Korean population.
Aged ; Asian Continental Ancestry Group/*genetics ; Carcinoma, Non-Small-Cell Lung/*genetics/mortality/pathology ; Demography ; Disease-Free Survival ; Female ; Genotype ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/*genetics/mortality/pathology ; Male ; Middle Aged ; *Polymorphism, Single Nucleotide ; Republic of Korea ; Smoking ; Wnt Signaling Pathway/*genetics

Vascular endothelial growth factor (VEGF) contributes to tumor angiogenesis. The role of VEGF single nucleotide polymorphisms (SNPs) in lung cancer susceptibility and its prognosis remains inconclusive and controversial. This study was performed to investigate whether VEGF polymorphisms affect survival outcomes of patients with early stage non-small cell lung cancer (NSCLC) after surgery. Three potentially functional VEGF SNPs (rs833061T>C, rs2010963G>C, and rs3025039C>T) were genotyped. A total of 782 NSCLC patients who were treated with surgical resection were enrolled. The association of the SNPs with overall survival (OS) and disease free survival (DFS) was analyzed. In overall population, none of the three polymorphisms were significantly associated with OS or DFS. However, when the patients were stratified by tumor histology, squamous cell carcinoma (SCC) and adenocarcinoma (AC) had significantly different OS (Adjusted hazard ratio [aHR] = 0.76, 95% CI = 0.56–1.03 in SCC; aHR = 1.33, 95% CI = 0.98–1.82 in AC; P for heterogeneity = 0.01) and DFS (aHR = 0.75, 95% CI = 0.58–0.97 in SCC; aHR = 1.26, 95% CI = 1.00–1.60 in AC; P for heterogeneity = 0.004) according to the rs833061T>C genotypes. Our results suggest that the prognostic role of VEGF rs833061T>C may differ depending on tumor histology.
Adenocarcinoma ; Carcinoma, Non-Small-Cell Lung* ; Carcinoma, Squamous Cell ; Disease-Free Survival ; Genotype ; Humans ; Lung Neoplasms ; Polymorphism, Single Nucleotide ; Population Characteristics ; Prognosis* ; Vascular Endothelial Growth Factor A*

BACKGROUND/AIMS: A number of genome-wide and candidate gene association studies have identified polymorphisms associated with telomere length in Caucasian populations. This study was conducted to determine the impacts of 17 polymorphisms identified in Caucasians on telomere length in a Korean population. METHODS: Ninety-four healthy individuals were enrolled in this study. Relative telomere length of chromosomes from peripheral blood samples was measured using quantitative polymerase chain reaction. RESULTS: Two polymorphisms, rs10936599 of MYNN and rs412658 of ZNF676, were found to be associated w ith telomere length (under dominant model, p = 0.04; under recessive model, p = 0.001). Three polymorphisms, rs2853669, rs7705526, and rs2736108, at the TERT locus were also associated with telomere length (under recessive model, p = 0.01, p = 0.02, and p = 0.01, respectively). The genotypes of the five polymorphisms associated with short telomere length were considered bad genotypes; telomere length was significantly decreased with increasing number of bad genotypes (p= 1.7 x 10(-5)). CONCLUSIONS: We have identified polymorphisms associated with telomere length in a Korean population.
Adult ; Aged ; Asian Continental Ancestry Group/*genetics ; Case-Control Studies ; DNA-Binding Proteins/genetics ; Female ; Genome-Wide Association Study ; Genotype ; Humans ; Kruppel-Like Transcription Factors/genetics ; Male ; Middle Aged ; Phenotype ; *Polymorphism, Single Nucleotide ; Republic of Korea ; Telomerase/genetics ; Telomere/*genetics/metabolism ; *Telomere Homeostasis ; Zinc Fingers

PURPOSE: Nowadays, chromosomal regions containing genes associated with the risk of lung cancer are identified by a number of genome-wide association studies (GWASs). As part of the study, GWAS has identified the association of six chromosomal regions, 1q23, 4q22, 4q31, 5p15, 6p21, and 15q25, as being associated with lung cancer risk in the European population. We investigated the impact of genetic variants identified in GWASs for lung cancer susceptibility on the survival outcomes in patients with early stage non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Three hundred and sixty-three patients with surgically resected NSCLC were enrolled. Eight single nucleotide polymorphisms (SNPs), rs2808630 on 1q23, rs7671167 on 4q22, rs1489759 and rs2202507 on 4q31, rs2736100 and rs402710 on 5p15, rs1052486 on 6p21 and rs16969968 on 15q25, were genotyped using a polymerase chain reaction-restriction fragment length polymorphism assay. The associations between genotypes and overall survival (OS) and disease-free survival (DFS) were analyzed. RESULTS: None of the eight SNPs were significantly associated with OS or DFS. In addition, when the patients were categorized according to age, gender, smoking status, tumor histology and pathologic stage, there were no significant associations between the eight SNPs and the survival outcomes. CONCLUSION: These results suggest that the genetic variants identified by GWASs for lung cancer susceptibility may not affect the prognosis of early stage NSCLC.
Carcinoma, Non-Small-Cell Lung ; Disease Susceptibility ; Disease-Free Survival ; Genome-Wide Association Study ; Genotype ; Humans ; Lung ; Lung Neoplasms ; Polymorphism, Single Nucleotide ; Prognosis ; Smoke ; Smoking

This is a cross-sectional observational study undertaken to explore the current prescription pattern of non-steroidal anti-inflammatory drugs (NSAIDs) and the prevalence of NSAID-induced gastrointestinal (GI) risk factors of orthopaedic patients in real clinical practice in Korea. Study cohort included 3,140 orthopaedic outpatients at 131 hospitals and clinics between January 2008 and August 2008. A self-administered questionnaire was completed by each patient and physician. A simplified risk scoring scale (the Standardized Calculator of Risk for Events; SCORE) was used to measure patients' risk for GI complications. The pattern of NSAIDs prescription was identified from medical recordings. Forty-five percents of the patients belonged to high risk or very high risk groups for GI complications. The cyclooxygenase-2 enzyme (COX-2) selective NSAID showed a propensity to be prescribed more commonly for high/very high GI risk groups, but the rate was still as low as 51%. In conclusion, physician's considerate prescription of NSAIDs with well-understanding of each patient's GI risk factors is strongly encouraged in order to maximize cost effectiveness and to prevent serious GI complications in Korea. Other strategic efforts such as medical association-led education programs and application of Korean electronic SCORE system to hospital order communication system (OCS) should also be accompanied in a way to promote physician's attention.
Adult ; Aged ; Aged, 80 and over ; Anti-Inflammatory Agents, Non-Steroidal/*adverse effects ; Cohort Studies ; Cross-Sectional Studies ; Cyclooxygenase 2/metabolism ; Cyclooxygenase 2 Inhibitors/adverse effects ; Drug Prescriptions ; Female ; Gastrointestinal Diseases/chemically induced/complications/*epidemiology ; Humans ; Male ; Middle Aged ; Musculoskeletal Diseases/complications/*drug therapy ; Prevalence ; Questionnaires ; Republic of Korea ; Risk Factors