Polymorphisms in Apoptosis-Related Genes and TP53 Mutations in Non-Small Cell Lung Cancer

Apoptosis plays an essential role in the elimination of mutated or transformed cells from the body. Therefore, polymorphisms of apoptosis-related genes may lead to an alteration in apoptotic capacity, thereby affecting the occurrence of TP53 mutations in lung cancer. We investigated the relationship between potentially functional polymorphisms of apoptosis-related genes and TP53 mutations in non-small cell lung cancer (NSCLC). Twenty-seven single nucleotide polymorphisms in 20 apoptosis-related genes were genotyped by a sequenome mass spectrometry-based genotyping assay in 173 NSCLCs and the associations with TP53 mutations in the entire coding exons (exons 2-11), including splicing sites of the gene, were analyzed. None of the 27 polymorphisms was significantly associated with the occurrence of TP53 mutations. This suggests that apoptosis-related genes may not play an important role in the occurrence of TP53 mutations in lung cancer

Telomerase Activity and the Risk of Lung Cancer

Telomerase play a key role in the maintenance of telomere length and chromosome integrity. We have evaluated the association between telomerase activity and the risk of lung cancer in peripheral blood. Telomerase activity in peripheral blood mononuclear cells was measured by a PCR-designed telomeric repeat amplification protocol in 63 lung cancer patients and 190 healthy controls that were matched for age, gender, and smoking status. Telomerase activity was significantly lower in the lung cancer patients than in controls (mean ± standard deviation; 1.32 ± 1.65 vs 2.60 ± 3.09, P < 1 × 10-4). When telomerase activity was categorized into quartiles based on telomerase activity in the controls, the risk of lung cancer increased as telomerase activity reduced (Ptrend = 1 × 10-4). Moreover, when the subjects were categorized based on the median value of telomerase activity, subjects with low telomerase activity were at a significantly increased risk of lung cancer compared to subjects with high telomerase activity (adjusted odds ratio = 3.05, 95% confidence interval = 1.60-5.82, P = 7 × 10-4). These findings suggest that telomerase activity may affect telomere maintenance, thereby contributing to susceptibility to lung cancer

SERPINE2 Polymorphisms and Chronic Obstructive Pulmonary Disease

A number of genome-wide linkage analyses have identified the 2q33.3-2q37.2 region as most likely to contain the genes that contribute to the susceptibility to chronic obstructive pulmonary disease (COPD). It was hypothesized that the SERPINE2 gene, which is one of the genes located at the 2q33.3-2q37.2 region, may act as a low-penetrance susceptibility gene for COPD. To test this hypothesis, the association of four SERPINE2 single nucleotide polymorphisms (SNPs; rs16865421A>G, rs7583463A>C, rs729631C>G, and rs6734100C>G) with the risk of COPD was investigated in a case-control study of 311 COPD patients and 386 controls. The SNP rs16865421 was associated with a significantly decreased risk of COPD in a dominant model for the polymorphic allele (adjusted odds ratio [OR]=0.66, 95% confidence interval [CI]=0.45-0.97, P=0.03). In haplotype analysis, the GACC haplotype carrying the polymorphic allele at the rs16865421 was associated with a significantly decreased risk of COPD when compared to the AACC haplotype (adjusted OR=0.58, 95% CI=0.38-0.89, P=0.01), and this effect was evident in younger individuals (adjusted OR=0.30, 95% CI=0.14-0.64, P=0.002). This study suggests that the SERPINE2 gene contributes to the susceptibility to COPD

Silicon Carbide Fabrication by Infiltration of Molten Fe-Si Alloy Through Two-Step Reaction Sintering

Wider application of silicon carbide (SiC) is anticipated for increasing the durability of various structural facilities. For this study, SiC was fabricated with decreased electrical resistivity for precision electrical discharge machining. Two-step reaction sintering by infiltration of molten Fe-Si alloy was applied for SiC fabrication. The procedure included first sintering at 973 K in Ar gas atmosphere and second sintering by spontaneous infiltration of molten Fe-75%Si alloy at 1693 K in vacuum. The sintered structure porosity became very low, forming 3C-type SiC. Results confirmed that molten Fe-75%Si alloy infiltration occurred because of reaction sintering. The electrical resistivity of the sintered SiC infiltrated by molten Fe-75%Si alloy can be improved to be two orders of magnitude lower than that by molten Si, consequently maintaining the high performance of SiC

A Panel of Genetic Polymorphism for the Prediction of Prognosis in Patients with Early Stage Non-Small Cell Lung Cancer after Surgical Resection

<div><p>Background</p><p>This study was conducted to investigate whether a panel of eight genetic polymorphisms can predict the prognosis of patients with early stage non-small cell lung cancer (NSCLC) after surgical resection.</p><p>Materials and Methods</p><p>We selected eight single nucleotide polymorphisms (SNPs) which have been associated with the prognosis of lung cancer patients after surgery in our previous studies. A total of 814 patients with early stage NSCLC who underwent curative surgical resection were enrolled. The association of the eight SNPs with overall survival (OS) and disease-free survival (DFS) was analyzed.</p><p>Results</p><p>The eight SNPs (<i>CD3EAP</i> rs967591, <i>TNFRSF10B</i> rs1047266, <i>AKT1</i> rs3803300, <i>C3</i> rs2287845, <i>HOMER2</i> rs1256428, <i>GNB2L1</i> rs3756585, <i>ADAMTSL3</i> rs11259927, and <i>CD3D</i> rs3181259) were significantly associated with OS and/or DFS. Combining those eight SNPs, we designed a prognostic index to predict the prognosis of patients. According to relative risk of death, a score value was assigned to each genotype of the SNPs. A worse prognosis corresponded to a higher score value, and the sum of score values of eight SNPs defined the prognostic index of a patient. When we categorized the patients into two groups based on the prognostic index, high risk group was significantly associated with worse OS and DFS compared to low risk group (aHR for OS = 2.21, 95% CI = 1.69–2.88, <i>P</i> = 8.0 x 10⁻⁹, and aHR for DFS = 1.58, 95% CI = 1.29–1.94, <i>P</i> = 1.0 x 10⁻⁵).</p><p>Conclusions</p><p>Prognostic index using eight genetic polymorphisms may be useful for the prognostication of patients with surgically resected NSCLC.</p></div