Telomeres play a key role in the maintenance of chromosome integrity and stability. There is growing evidence that short telomeres induce chromosome instability and thereby promote the development of cancer. We investigated the association of telomere length and the risk of lung cancer. Relative telomere length in peripheral blood lymphocytes was measured by quantitative polymerase chain reaction in 243 lung cancer patients and 243 healthy controls that were frequency‐matched for age, sex and smoking status. Telomere length was significantly shorter in lung cancer patients than in controls (mean ± standard deviation: 1.59 ± 0.75versus2.16 ± 1.10,P < 0.0001). When the subjects were categorized into quartiles based on telomere length, the risk of lung cancer was found to increase as telomere length shortened (P_trend< 0.0001). In addition, when the median of telomere length was used as the cutoff between long and short telomeres, individuals with short telomeres were at a significantly higher risk of lung cancer than those with long telomeres (adjusted odds ratio = 3.15, 95% confidence interval = 2.12–4.67,P < 0.0001). When the cases were categorized by tumor histology, the effect of short telomere length on the risk of lung cancer was more pronounced in patients with small cell carcinoma than in those with squamous cell carcinoma and adenocarcinoma (P = 0.001, test for homogeneity). These findings suggest that shortening of the telomeres may be a risk factor for lung cancer, and therefore, the presence of shortened telomeres may be used as a marker for susceptibility to lung cancer. (Cancer Sci2008; 99: 1385–1389)

Epidermal growth factor receptor (EGFR) signaling pathway plays a crucial role in many carcinogenic processes such as proliferation, angiogenesis, invasion, and metastasis, and resistance to apoptosis.¹ x 1 Yarden, Y and Sliwkowski, MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2001; 2: 127–137 Crossref | PubMed | Scopus (4617) | Google Scholar See all References ^{, 2} x 2 Rowinsky, EK. The erbB family: targets for therapeutic development against cancer and therapeutic strategies using monoclonal antibodies and tyrosine kinase inhibitors. Annu Rev Med. 2004; 55: 433–457 Crossref | PubMed | Scopus (158) | Google Scholar See all References RAS/RAF/mitogen activated protein kinase (MAPK), phosphatidylinosital 3-kinase (P13K)/AKT, signal transducer and activator of transcription, v-src sarcoma viral oncogene homolog (SRC)/focal adhesion kinase (FAK), and phospholipase C pathways are known downstream signaling cascades transducing EGFR activation signals, with RAS/RAF/MAPK and PI3K/AKT being the two major pathways.³ x 3 Wieduwilt, MJ and Moasser, MM. The epidermal growth factor receptor family: biology driving targeted therapeutics. Cell Mol Life Sci. 2008; 65: 1566–1584 Crossref | PubMed | Scopus (183) | Google Scholar See all References ^{, 4} x 4 Laurent-Puig, P, Lievre, A, and Blons, H. Mutations and response to epidermal growth factor receptor inhibitors. Clin Cancer Res. 2009; 15: 1133–1139 Crossref | PubMed | Scopus (101) | Google Scholar See all References

BACKGROUND.: Lung cancer is the leading cause of cancer deaths worldwide. The epigenetic inactivation of certain genes by aberrant promoter methylation plays an important role in the pathogenesis of lung cancer. In addition, DNA hypermethylation is an extremely promising cancer marker. Cadherins are cell adhesion molecules that modulate the epithelial phenotype and regulate tumor invasion. Although the aberrant methylation of E‐cadherin (CDH1) or H‐cadherin (CDH13) genes has been reported in lung cancer, to the authors' knowledge, the relation between the concurrent hypermethylation in E‐cadherin and H‐cadherin has not been explored to date.METHODS.: The authors investigated the methylation status of the promoter region of human E‐cadherin and H‐cadherin genes in resected samples of primary nonsmall cell lung cancer (NSCLC) using methylation‐specific polymerase chain reaction (MSP) analysis and correlated the results with clinicopathologic characteristics. The methylation status of the promoter regions of the E‐cadherin and H‐cadherin genes was examined by using nested MSP in 88 primary lung cancers and paired adjacent normal tissues. Data were compared with clinicopathologic features.RESULTS.: The frequency of methylation in neoplastic and corresponding nonneoplastic lung tissues was 30 of 88 tissue samples (34.1%) and 5 of 88 tissue samples (5.7%) for E‐cadherin and 26 of 88 tissue samples (29.5%) and 7 of 88 tissue samples (8%) for H‐cadherin, respectively. In addition, in 9 patients (10.2%), both genes were methylated. Although there was no significant difference in the overall survival of patients according to the methylation pattern of the E‐cadherin gene alone or the H‐cadherin gene alone, patients with NSCLC who had hypermethylation of both genes had a significantly longer overall survival. However, no correlation was observed between their methylation status and any other clinicopathologic factors.CONCLUSIONS.: The current findings suggested that simultaneous methylation of the E‐cadherin and H‐cadherin genes occurs in a subset of NSCLCs and may be used as a prognostic marker for patients with NSCLC. However, further studies with large numbers of patients will be needed to confirm the findings. Cancer 2007. © 2007 American Cancer Society.

Although TP53 mutations have been widely studied in lung cancer, the majority of studies have focused on exons 5-8 of the gene. In addition, TP53 mutations in Korean patients with lung cancers have not been investigated. We searched for mutations in the entire coding exons, including splice sites of the gene, in Korean patients with non-small cell lung cancer (NSCLC). Mutations of the gene were determined by direct sequencing in 176 NSCLCs. Sixty-nine mutations (62 different mutations) were identified in 65 tumors. Of the 62 mutations, 12 were novel mutations. TP53 mutations were more frequent in males, ever-smokers and squamous cell carcinomas than in females, never-smokers and adenocarcinomas, respectively (all comparisons, P<0.001). Missense mutations were most common (52.2%), but frameshift, nonsense, and splice-site mutations were frequently observed at frequencies of 18.8%, 15.9% and 10.1%, respectively. Of the 69 mutations, 9 (13.0%) were found in the oligomerization domain. In addition, the proportion of mutations in the oligomerization domain was significantly higher in adenocarcinomas than in squamous cell carcinomas (23.5% vs. 2.9%, P=0.01). Our study provides clinical and molecular characteristics of TP53 mutations in Korean patients with NSCLCs.

Multidrug resistance‐1 (MDR‐1) gene single nucleotide polymorphisms (SNPs) have been identified as associated with the treatment outcomes of acute myeloid leukemia (AML) in Caucasians; yet, similar evidence is lacking for Asian populations. A total of 101 AML patients were enrolled in the current study. Two MDR1 SNPs (C3435T and G2677T/A) were analyzed with PCR/RFLP assay. As regards C3435T polymorphism, C/C genotype was significantly correlated with lower functional P‐glycoprotein (P‐gp) activity in leukemic blasts (7.5%) compared with C/T (10.7%) or T/T genotype (19.9%, p = 0.029). In genotypic analyses, C/C at −3435 (p = 0.05) and G/G at −2677 (p = 0.04) were strongly associated with a higher probability of complete remission (CR). In addition, the 3‐year event‐free survival (EFS) was higher in G/G genotype at −2677 (60.6%) than nonG/G (21.9%; p = 0.0241), in C/C at −3435 was higher than nonC/C genotype (p = 0.0139), and was higher in GC haplotype homozygote (58.2%) than nonGC homozygote (22.6%; p = 0.0427). In a multivariate analysis, the group without GC haplotype showed worse EFS (p = 0.030), with unfavorable cytogenetic risk (p = 0.008). However, no differences were noted in overall survival according to the MDR1 SNPs (p = 0.491 for C3435T and p = 0.955 for G2677T/A).