Lung cancer is the most common cause of death from cancer worldwide, and its incidence is increasing in East Asian and Western countries. To identify genetic factors that modify the risk of lung adenocarcinoma, we conducted a genome-wide association study in a Japanese cohort, with replication in two independent studies in Japanese and Korean individuals, in a total of 2,098 lung adenocarcinoma cases and 11,048 controls. The combined analyses identified two susceptibility loci for lung adenocarcinoma: TERT (rs2736100, combined P = 2.91 × 10⁻¹¹), odds ratio (OR) = 1.27) and TP63 (rs10937405, combined P = 7.26 × 10⁻¹²), OR = 1.31). Fine mapping of the region containing TP63 showed that a SNP (rs4488809) in intron 1 of TP63 showed the most significant association. Our results suggest that genetic variation in TP63 may influence susceptibility to lung adenocarcinoma in East Asian populations.
In this paper we are concerned with the design, manufacture and performance test of a lightweight piezo-composite curved actuator (called LIPCA) using a top carbon fiber composite layer with near-zero coefficient of thermal expansion (CTE), a middle PZT ceramic wafer, and a bottom glass/epoxy layer with a high CTE. The main point of the design for LIPCA is to replace the heavy metal layers of THUNDER TM by lightweight fiber reinforced plastic layers without losing the capabilities for generating high force and large displacement. It is possible to save up to about 40% of the weight if we replace the metallic backing material by the light fiber composite layer. We can also have design flexibility by selecting the fiber direction and the size of prepreg layers. In addition to the lightweight advantage and design flexibility, the proposed device can be manufactured without adhesive layers when we use an epoxy resin prepreg system. Glass/epoxy prepregs, a ceramic wafer with electrode surfaces, and a carbon prepreg were simply stacked and cured at an elevated temperature (177 • C) after following an autoclave bagging process. We found that the manufactured composite laminate device had a sufficient curvature after being detached from a flat mould. An analysis method using the classical lamination theory is presented to predict the curvature of LIPCA after curing at an elevated temperature. The predicted curvatures are in quite good agreement with the experimental values. In order to investigate the merits of LIPCA, performance tests of both LIPCA and THUNDER TM have been conducted under the same boundary conditions. From the experimental actuation tests, it was observed that the developed actuator could generate larger actuation displacement than THUNDER TM .
Our findings suggest that polymorphisms in the rs2910164 of miR-146a and the rs11614913 of miR-196a2 are associated with prognosis in patients with completely resected NSCLC.
Gastric cancer is the most common cancer in Korea. Germline mutations of the E-cadherin gene have recently been identified in familial gastric cancer patients. We screened five Korean familial gastric cancer patients to investigate germline mutations of the E-cadherin gene. These patients fulfilled the following criteria: presence of at least two gastric cancer patients within first-degree relatives and one patient diagnosed before the age of 50 years. Abnormal band patterns were found in exons 6 and 10 in two familial gastric cancer patients by polymerase chain reaction-single strand conformation polymorphism analysis (probands from the SNU-G2 and SNU-G1001 families, respectively). DNA sequencing analysis of the E-cadherin gene of these two patients revealed missense mutations in each exon. The SNU-G2 proband harbored a missense mutation from aspartic acid (GAT) to glycine (GGT) at codon 244 in exon 6 of the E-cadherin gene, and the SNU-G1001 proband had a missense mutation from valine (GTG) to alanine (GCG) at codon 487 in exon 10. The SNU-G2 proband was diagnosed with gastric cancer at the age of 38; three brothers and two sisters had died of gastric cancer under the age of 50, and their mother had died of gastric cancer at the age of 63. The SNU-G1001 proband was diagnosed with gastric cancer at the age of 42 and one brother had died of gastric cancer at the age of 49. In summary, we found germline mutations of the E-cadherin gene in two of five Korean familial gastric cancer patients screened.
Lung cancer is one of the most common cancers and the major cause of cancer death, both in Korea and worldwide, with non-small cell lung cancer (NSCLC) as the predominant histologic type. To identify genetic risk factors, we here conducted a genome-wide association study (GWAS) and a replication study in 1425 patients with NSCLC and 3011 controls from Korea. From the data for 2162 participants analyzed using the Affymetrix Genome-wide Human SNP array 5.0K, 168 single nucleotide polymorphisms (SNPs) were selected for validation. In the second stage, we were able to genotype 168 SNPs in 804 patients and 1470 controls to confirm the results of the GWAS. In the meta-analysis, rs2131877 at the chromosome 3q29 region was the most significant biomarker of lung cancer susceptibility in Koreans (P = 2.43 × 10(-8)). Four markers that were located within the chromosome 3q29 region were also associated with lung cancer susceptibility (trend P < 1.2 × 10(-4)), along with markers on 5p15 that were previously reported in populations of European descent. This high-density large-scale GWAS carried out in the Korean population suggests that 3q29 is a novel susceptibility region associated with lung cancer susceptibility in Koreans.
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