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.

Genetic Variants in the Wnt Signaling Pathway Are Not Associated with Survival Outcome of Non-Small Cell Lung Cancer in a Korean Population

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.

The Different Effect of VEGF Polymorphisms on the Prognosis of Non-Small Cell Lung Cancer according to Tumor Histology

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.

Sudden Hearing Loss in Chronic Myelogenous Leukemia Implicating Hyperviscosity Syndrome / 대한이비인후과학회지

Sudden sensorineural hearing loss due to the initial manifestation of hematologic disease is very rare. Chronic myelogenous leukemia has been implicated as a causative factor of sudden sensorineural hearing loss. Leukemic infiltration, hemorrhage, infection, and hyperviscosity have been suggested as possible mechanisms in patients with chronic myelogenous leukemia. A 49-year-old male presented unilateral sudden sensorineural hearing loss. The patient was found to have chronic myelogenous leukemia during the work-up for the hearing loss. The WBC count upon admission was 485,100/mm(3). Hemoglobin, hematocrit, and platelet count were within the normal limits. The patient underwent three cycles of leukapheresis and chemotherapy with interferon alpha and hydroxyurea for the treatment of leukemia. The hearing threshold level was 75 dB on admission. It improved to 35 dB when the WBC count fell to 294,000/mm(3), and finally settled at 32 dB two weeks after the termination of chemotherapy when the WBC count was 125,900/mm(3). We present a case of a chronic myelogenous leukemia patient who initially presented with sudden sensorineural hearing loss. We presume that cochlear vessel occlusion as a result of elevated blood viscosity was responsible for this patient's hearing loss. Early onset of sudden deafness in a chronic myelogenous leukemia patient may be due to the hyperviscosity syndrome and be possible to reverse hearing loss through early leukapheresis.

Two Cases of Renal Cell Carcinoma Metastatic to the Thyroid Gland / 대한이비인후과학회지

Metastatic cancers to the thyroid gland are rare, with the most common primary site being the kidney. The next most common sites are the breast, lung, melanoma, colon and larynx. In the case of thyroid metastasis of renal cell carcinoma, the thyroid metastasis may be the initial manifestation and the incidence of this type seems disproportionate to the frequency of the primary renal cell carcinoma. 3Ve have recently experienced two cases of thyroid metastasis of renal cell carcinoma and report them with a brief review of the related literature.