Promoter-Specific Variants in NeuroD1 and H3K4me3 Coincident Regions and Clinical Outcomes of Small Cell Lung Cancer

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 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 G and CINP rs762105A>G were associated with clinical outcomes in patients with SCLC and also affected the promoter activity of each gene.

The effect of susceptibility variants, identified in never-smoking female lung cancer cases, on male smokers

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.

TERT Polymorphism rs2853669 Influences on Lung Cancer Risk in the Korean Population

Short telomeres are known as one of the risk factors for human cancers. The present study was conducted to evaluate the association between 6 polymorphisms, which were related with short telomere length in the Korean population, and lung cancer risk using 1,100 cases and 1,096 controls. Among the 6 polymorphisms, TERT rs2853669 was significantly associated with increased lung cancer risk under a recessive model (odds ratio [OR]=1.38, 95% confidence interval [CI]=1.05-1.81, P=0.02). The effect of rs2853669 on lung cancer risk was significant in younger individuals (OR=1.73, 95% CI=1.18-2.54, P=0.005) and adenocarcinoma (OR=1.50, 95% CI=1.07-2.07, P=0.02). Our results suggest that a common functional promoter polymorphism, TERT rs2853669, may influence both telomere length and lung cancer risk in the Korean population.

Replication of the results of genome-wide and candidate gene association studies on telomere length in a Korean population

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.

Association between Lung Cancer Susceptibility Variants Identified by Genome-Wide Association Studies and the Survival of Non-Small Cell Lung Cancer

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.