Genome-wide association studies (GWASs) have already identified at least 22 common susceptibility loci associated with an increased risk of colorectal cancer (CRC). This study examined the relationship between these single nucleotide polymorphisms (SNPs) and the clinical outcomes of patients with colorectal cancer. Seven hundred seventy-six patients with surgically resected colorectal adenocarcinoma were enrolled in the present study. Twenty-two of the GWAS-identified SNPs were genotyped using a Sequenom MassARRAY. Among the 22 SNPs, two (rs1321311G>T in CDKN1A and rs10411210C>T in RHPN2) were significantly associated with the survival outcomes of CRC in a multivariate survival analysis. In a recessive model, the rs1321311 TT genotype (vs. GG + GT) and rs10411210 TT genotype (vs. CC + CT) were associated with a worse prognosis for disease-free survival (adjusted HR = 1.90; 95% confidence interval = 1.00-3.60; P = 0.050, adjusted HR = 1.94; 95% confidence interval = 1.05-3.57; P = 0.034, respectively) and overall survival (adjusted HR = 2.05; 95% confidence interval = 1.00-4.20; P = 0.049, adjusted HR = 2.06; 95% confidence interval = 1.05-4.05; P = 0.036, respectively). None of the other SNPs was significantly associated with any clinicopathologic features or survival. The present results suggest that the genetic variants of the CDKN1A (rs1321311) and RHPN2 (rs10411210) genes can be used as prognostic biomarkers for patients with surgically resected colorectal cancer.

MicroRNAs (miRs) play important roles in the development and progression of human cancers. MiR-146a down-regulates epidermal growth factor receptor and the nuclear factor-κB regulatory kinase interleukin-1 receptor-associated kinase 1 genes that play important roles in lung carcinogenesis. This study was conducted to evaluate the association between rs2910164C>G, a functional polymorphism in the pre-miR-146a, and lung cancer risk.

Therapeutic agents that are transformable via introducing cleavable linkage by locally enriched MMP-2 within inflamed synovium would enhance therapeutic efficacy on chronic inflammatory arthritis. Transforming growth factor-β-inducible gene-h3 (βig-h3), which consists of four fas-1 domains and an Arg-Gly-Asp (RGD) motif, intensifies inflammatory processes by facilitating adhesion and migration of fibroblast-like synoviocyte in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to investigate whether a MMP-2-cleavable peptide complex consisting of a fas-1 domain and an RGD peptide blocks the interaction between βig-h3 and resident cells and leads to the amelioration of inflammatory arthritis.

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.

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.

The lung cancer mortality in Korea has increased remarkably during the last 20 years, and has been the first leading cause of cancer-related deaths since 2000. The aim of the current study was to examine the time trends of occupational lung cancer and carcinogens exposure during the period 2006-2009 in South Korea, by assessing the proportion of occupational burden.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide and has high rates of metastasis. Transforming growth factor beta-inducible protein (TGFBI) is an extracellular matrix component involved in tumour growth and metastasis. However, the exact role of TGFBI in NSCLC remains controversial. Gene silencing via DNA methylation of the promoter region is common in lung tumorigenesis and could thus be used for the development of molecular biomarkers. We analysed the methylation status of the TGFBI promoter in 138 NSCLC specimens via methylation-specific PCR and evaluated the correlation between TGFBI methylation and patient survival. TGFBI promoter methylation was detected in 25 (18.1%) of the tumours and was demonstrated to be associated with gene silencing. We observed no statistical correlation between TGFBI methylation and clinicopathological characteristics. Univariate and multivariate analyses showed that TGFBI methylation is significantly associated with poor survival outcomes in adenocarcinoma cases (adjusted hazard ratio = 2.88, 95% confidence interval = 1.19-6.99, P = 0.019), but not in squamous cell cases. Our findings suggest that methylation in the TGFBI promoter may be associated with pathogenesis of NSCLC and can be used as a predictive marker for lung adenocarcinoma prognosis. Further large-scale studies are needed to confirm these findings.

A high-throughput mapping method of RNA-RNA interactions by crosslinking, ligation, and sequencing of hybrids (CLASH) can not only provide information about canonical but also non-canonical interactions. We evaluated the associations between variants in microRNA target sites using CLASH data and survival outcomes of 782 early-stage non-small cell lung cancer (NSCLC) patients who underwent curative surgical resection. Among the 100 variants studied, two variants showed significant association with survival outcomes. The POLR2A rs2071504 C > T variant was associated with poor overall and disease-free survival under a dominant model (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.08-1.88; P = 0.01 and HR 1.34, 95% CI 1.08-1.67; P = 0.01, respectively). Patients carrying the NR2F6 rs2288539 TT genotype showed significantly better overall survival than those with the NR2F6 rs2288539 CC or CT genotypes (HR 0.13, 95% CI 0.02-0.90; P = 0.04). These findings suggest that POLR2A rs2071504 C > T and NR2F6 rs2288539 C > T can influence prognosis in early-stage NSCLC patients.

We investigated whether genetic susceptibility to tuberculosis (TB) influences lung adenocarcinoma development among never-smokers using TB genome-wide association study (GWAS) results within the Female Lung Cancer Consortium in Asia. Pathway analysis with the adaptive rank truncated product method was used to assess the association between a TB-related gene-set and lung adenocarcinoma using GWAS data from 5512 lung adenocarcinoma cases and 6277 controls. The gene-set consisted of 31 genes containing known/suggestive associations with genetic variants from previous TB-GWAS. Subsequently, we followed-up with Mendelian Randomization to evaluate the association between TB and lung adenocarcinoma using three genome-wide significant variants from previous TB-GWAS in East Asians. The TB-related gene-set was associated with lung adenocarcinoma (p = 0.016). Additionally, the Mendelian Randomization showed an association between TB and lung adenocarcinoma (OR = 1.31, 95% CI: 1.03, 1.66, p = 0.027). Our findings support TB as a causal risk factor for lung cancer development among never-smoking Asian women.

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.

Genetic polymorphism can result in abnormal pharmacodynamics that subsequently leads to the individual variance in sedative effects and adverse reactions. The aim of this study was to elucidate the association between midazolam-related genetic polymorphism and sedative effects, including adverse reactions, under conscious sedation during upper gastrointestinal endoscopy. We prospectively enrolled 100 eligible patients undergoing upper gastrointestinal endoscopy. The efficacy of the sedation, adverse reactions, plasma concentration of midazolam and 1-hydroxymidazolam were investigated as well as the genetic polymorphism of MDR1 and CYP3A5. The correlation between genetic polymorphism and sedative effects was assessed. Regarding MDR1 gene, the plasma concentration of midazolam was greater in patients with CGC haplotype (P = 0.012), while it was lower in patients with CAC haplotype (P = 0.005) than in those with other haplotypes. However, genetic polymorphism of neither MDR1 nor CYP3A5 correlated with the plasma concentration of 1-hydroxymidazolam. CGT haplotype of MDR1 was significantly correlated with sedation grade after midazolam administration (P = 0.042). In contrast, genetic polymorphism of CYP3A5 was not correlated with sedation grade. There was no association between genetic polymorphism of MDR1 or CYP3A5 and selected adverse reactions related to midazolam. Genetic polymorphism of MDR1 influences the concentration of midazolam and the sedation grade. However, it is not associated with adverse reactions such as paradoxical response and retrograde amnesia.

After endoscopic resection (ER) of gastric dysplasia, metachronous gastric neoplasm (MGN) appears to have an incidence rate similar to that detected after ER of early gastric cancer (EGC). We investigated whether the risk of MGN after ER for gastric dysplasia is different between patients with low-grade dysplasia (LGD) and high-grade dysplasia (HGD). Between March 2011 and December 2016, 198 patients with LGD (LGD group) and 46 patients with HGD (HGD group) who underwent ER were included in the study. During a median follow-up of 2.5 years, MGNs developed in 21 patients (10.6%) in the LGD group and in 6 patients (13.0%) in the HGD group. Hazard ratios (HRs) for MGNs (HR, 1.45; P = 0.425) and for metachronous HGD or gastric cancer (HR, 2.41; P = 0.214) in the HGD group were not different than those of the LGD group. However, considering patients without Helicobacter pylori infection, those in the HGD group had a significantly increased risk of metachronous HGD or gastric cancer compared to those in the LGD group (HR in HGD-group, 5.23; P = 0.044). These results indicate that meticulous surveillance endoscopy is needed to detect MGNs after ER of gastric dysplasia, especially in patients with HGD, including those without H. pylori infection.

Cancer screening and diagnosis can be achieved by analyzing specific molecules within serum-derived extracellular vesicles (EVs). This study sought to profile EV-derived proteins to identify potential lung cancer biomarkers. EVs were isolated from 80 serum samples from healthy individuals and cancer patients via polyethylene glycol (PEG)-based precipitation and immunoaffinity separation using antibodies against CD9, CD63, CD81, and EpCAM. Proteomic analysis was performed using 2-D gel electrophoresis and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS). The expression of proteins that were differentially upregulated in the EVs or tissue of lung cancer samples was validated by Western blotting. The area under the curve (AUC) was calculated to assess the predictability of each differentially expressed protein (DEP) for lung cancer. A total of 55 upregulated protein spots were selected, seven of which (CD5L, CLEC3B, ITIH4, SERFINF1, SAA4, SERFINC1, and C20ORF3) were found to be expressed at high levels in patient-derived EVs by Western blotting. Meanwhile, only the expression of EV CD5L correlated with that in cancer tissues. CD5L also demonstrated the highest AUC value (0.943) and was found to be the core regulator in a pathway related to cell dysfunction. Cumulatively, these results show that EV-derived CD5L may represent a potential biomarker-detected via a liquid biopsy-for the noninvasive diagnosis of lung cancer.

To investigate the impact of programmed death-ligand 1 (PD-L1) polymorphisms on the prognosis of non-small cell lung cancer (NSCLC) patients treated with curative radiotherapy.

Despite therapeutic advances, lung cancer prognosis remains poor. Loss of heterozygosity (LOH) in the 3p21 region is well documented in lung cancer, but the specific causative genes have not been identified.

This study aimed to determine if 3D printing can affect surgeon's selection of plate for distal tibia fracture surgery and to find out whether orthopedic surgeons consider this technology necessary and would use it in their practice. A total of 102 orthopedic surgeons were asked to choose anatomically contoured locking plates among 5 most commonly used types for one simple and one complex distal tibia fracture based on X-ray and CT images. Next, they were provided real-size 3D printed models of the same fractures, allowed to apply each of the 5 plates to these models, and asked if they would change their choice of plate. A 10-point numeric rating scale was provided to measure the extent of the help that 3D printing provided on preoperative planning. Finally, we asked the surgeons if they would use 3D printing in their practice. Seventy-four percent of inexperienced surgeons changed their selection of plate after using 3D printed models for the complex fracture. In contrast, only 9% of experienced surgeons changed their selection of plate for the simple fracture. Surgeons rated the extent of usefulness of the 3D models in preoperative planning as a mean of 4.84 ± 2.54 points for the simple fracture and 6.63 ± 2.54 points for the complex fracture. The difference was significant (p < 0.001). Eighty-six percent of inexperienced surgeons wanted to use 3D models for complex fractures. However, only 18% of experienced surgeons wanted to use 3D printed models for simple fractures. The use of a real-size 3D-printed model often changed surgeon's preoperative selection of locking plates, especially when inexperienced surgeons evaluated a complex fracture. However, experienced surgeons did not find 3D models very useful when assessing simple fractures. Future applications of 3D models should focus on training beginners in fracture surgery, especially when complex fractures are concerned.

Individuals can be infected with multiple strains of Helicobacter pylori. However, the differences among co-infecting strains have not been well analyzed yet. This study aimed to investigate whether the virulence factors and antibiotic resistance patterns of H. pylori differ between strains isolated from different locations of the stomach in the same patient.

The present study was performed to investigate the association of single nucleotide polymorphisms (SNPs) located in the miRNA target sites with the clinical outcomes of first line paclitaxel-cisplatin chemotherapy in advanced NSCLC. Eighty SNPs in miRNA binding sites of cancer related genes selected from 18,500 miRNA:target bindings in crosslinking, ligation, and sequencing of hybrids (CLASH) data were investigated in 379 advanced NSCLC patients using a sequenom mass spectrometry-based genotype assay. qRT-PCR and luciferase assay were conducted to examine functional relevance of potentially functional SNPs in miRNA binding sites. Of the 80 SNPs analyzed, 16 SNPs were significantly associated with the clinical outcomes after chemotherapy. Among these, ANAPC1 rs3814026C>T, ETS2 rs461155A>G, SORBS1 rs7081076C>A and POLR2A rs2071504C>T could predict both chemotherapy response and survival. Notably, ETS2 rs461155A>G was significantly associated with decreased ETS2 mRNA expression in both tumor and paired normal lung tissues (Ptrend = 4 × 10-7, and 3 × 10-4, respectively). Consistently, a decreased expression of the reporter gene for the G allele of rs461155 compared with the A allele was observed by luciferase assay. These findings suggest that the four SNPs, especially ETS2 rs461155A>G, could be used as biomarkers predicting the clinical outcomes of NSCLC patients treated with first-line paclitaxel-cisplatin chemotherapy.

Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 × 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.

Genome-wide association studies have indicated that most of the currently identified disease and trait-associated single nucleotide polymorphisms (SNPs) are intronic or intergenic. RegulomeDB is a recently developed database that provides functional annotations for regulatory features of SNPs located in non-coding regions. We evaluated the potential regulatory SNPs in the EGFR gene region using RegulomeDB and their associations with prognosis after surgery in non-small cell lung cancer (NSCLC) patients.