Genetic Polymorphisms of CYP2E1, GSTP1, NQO1 and MPO and the Risk of Nasopharyngeal Carcinoma in a Han Chinese Population of Southern China

<p>Abstract</p> <p>Background</p> <p>Southern China is a major area for endemic nasopharyngeal carcinoma (NPC). Genetic factors as well as environmental factors play a role in development of NPC. To investigate the roles of previously described carcinogen metabolism gene variants for NPC susceptibility in a Han Chinese population, we conducted a case-control study in two independent study population groups afflicted with NPC in Guangdong and Guangxi Provinces of southern China.</p> <p>Methods</p> <p>Five single nucleotide polymorphisms (SNPs) of <it>CYP2E1</it>-rs2031920, <it>CYP2E1</it>-rs6413432, <it>GSTP1</it>-rs947894, <it>MPO</it>-rs2333227 and <it>NQO1</it>-rs1800566 were genotyped by PCR-based RFLP, sequencing and TaqMan assay in 358 NPC cases and 629 controls (phase I cohort). Logistic regression analysis was used to estimate odds ratios (OR) and 95% confidence intervals (CI). To confirm our results, sixteen tag SNPs for <it>GSTP1</it>, <it>MPO</it>, <it>NQO1 </it>(which 100% covered these genes), and 4 functional SNPs of <it>CYP2E1 </it>were genotyped in another cohort of 213 NPC cases and 230 controls (phase II cohort).</p> <p>Results</p> <p>No significant associations in NPC risk were observed for the five polymorphisms tested in the phase I cohort. In an additional stratified analysis for phase I, there was no significant association between cases and controls in NPC high risk population (EBV/IgA/VCA positive population). Analysis of 14 tagging SNPs within the same genes in an independent phase II cohort were in agreement with no SNPs significantly associated with NPC.</p> <p>Conclusions</p> <p>Our results suggest that polymorphism of <it>CYP2E1</it>, <it>GSTP1</it>, <it>MPO </it>and <it>NQO1 </it>genes does not contribute to overall NPC risk in a Han Chinese in southern China.</p

Single Molecule PCR Reveals Similar Patterns of Non-Homologous DSB Repair in Tobacco and Arabidopsis

DNA double strand breaks (DSBs) occur constantly in eukaryotes. These potentially lethal DNA lesions are repaired efficiently by two major DSB repair pathways: homologous recombination and non-homologous end joining (NHEJ). We investigated NHEJ in Arabidopsis thaliana and tobacco (Nicotiana tabacum) by introducing DNA double-strand breaks through inducible expression of I-SceI, followed by amplification of individual repair junction sequences by single-molecule PCR. Using this process over 300 NHEJ repair junctions were analysed in each species. In contrast to previously published variation in DSB repair between Arabidopsis and tobacco, the two species displayed similar DSB repair profiles in our experiments. The majority of repair events resulted in no loss of sequence and small (1–20 bp) deletions occurred at a minority (25–45%) of repair junctions. Approximately ∼1.5% of the observed repair events contained larger deletions (>20 bp) and a similar percentage contained insertions. Strikingly, insertion events in tobacco were associated with large genomic deletions at the site of the DSB that resulted in increased micro-homology at the sequence junctions suggesting the involvement of a non-classical NHEJ repair pathway. The generation of DSBs through inducible expression of I-SceI, in combination with single molecule PCR, provides an effective and efficient method for analysis of individual repair junctions and will prove a useful tool in the analysis of NHEJ

Long interspersed nuclear element-1 hypomethylation in cancer: biology and clinical applications

Epigenetic changes in long interspersed nuclear element-1s (LINE-1s or L1s) occur early during the process of carcinogenesis. A lower methylation level (hypomethylation) of LINE-1 is common in most cancers, and the methylation level is further decreased in more advanced cancers. Consequently, several previous studies have suggested the use of LINE-1 hypomethylation levels in cancer screening, risk assessment, tumor staging, and prognostic prediction. Epigenomic changes are complex, and global hypomethylation influences LINE-1s in a generalized fashion. However, the methylation levels of some loci are dependent on their locations. The consequences of LINE-1 hypomethylation are genomic instability and alteration of gene expression. There are several mechanisms that promote both of these consequences in cis. Therefore, the methylation levels of different sets of LINE-1s may represent certain phenotypes. Furthermore, the methylation levels of specific sets of LINE-1s may indicate carcinogenesis-dependent hypomethylation. LINE-1 methylation pattern analysis can classify LINE-1s into one of three classes based on the number of methylated CpG dinucleotides. These classes include hypermethylation, partial methylation, and hypomethylation. The number of partial and hypermethylated loci, but not hypomethylated LINE-1s, is different among normal cell types. Consequently, the number of hypomethylated loci is a more promising marker than methylation level in the detection of cancer DNA. Further genome-wide studies to measure the methylation level of each LINE-1 locus may improve PCR-based methylation analysis to allow for a more specific and sensitive detection of cancer DNA or for an analysis of certain cancer phenotypes

Molecularly Imprinted Polymer-Based Optical Sensor for Isopropanol Vapor

Recent advances have allowed the monitoring of several volatile organic compounds (VOCs) in human exhaled breath, and many of them are being utilized as a biomarker to diagnose several diseases, including diabetes. Among several VOCs, isopropanol (IPA) has been reported as a common volatile compound in the exhaled breath of patients with type 1 and type 2 diabetes. In this article, an experimental approach is discussed to develop a highly selective and sensitive IPA vapor sensor system. The fabricated sensor is comprised of a small and portable glass slide coated with molecularly imprinted polymer containing specific binding sites compatible with IPA molecules. The developed sensor is based on the wavelength interrogation technique. The fabricated device is analyzed for the detection of IPA vapor with different concentrations varying from 50% to 100%. The sensor exhibits maximum sensitivities of 0.37, 0.30, and 0.62 nm/%IPA, respectively, for 30, 60, and 90 min, respectively, and an excellent sensitivity of 0.63 nm/%IPA for 120 min exposure along with good selectivity among a similar class of VOCs. The major features of the sensor i.e., small size, portability, cost-effectiveness, high sensitivity, and good selectivity, make it a potential candidate for diabetes monitoring. The promising results of the sensor illustrate its potential in diabetes monitoring applications

Molecularly Imprinted Polymer-Based Optical Sensor for Isopropanol Vapor

Recent advances have allowed the monitoring of several volatile organic compounds (VOCs) in human exhaled breath, and many of them are being utilized as a biomarker to diagnose several diseases, including diabetes. Among several VOCs, isopropanol (IPA) has been reported as a common volatile compound in the exhaled breath of patients with type 1 and type 2 diabetes. In this article, an experimental approach is discussed to develop a highly selective and sensitive IPA vapor sensor system. The fabricated sensor is comprised of a small and portable glass slide coated with molecularly imprinted polymer containing specific binding sites compatible with IPA molecules. The developed sensor is based on the wavelength interrogation technique. The fabricated device is analyzed for the detection of IPA vapor with different concentrations varying from 50% to 100%. The sensor exhibits maximum sensitivities of 0.37, 0.30, and 0.62 nm/%IPA, respectively, for 30, 60, and 90 min, respectively, and an excellent sensitivity of 0.63 nm/%IPA for 120 min exposure along with good selectivity among a similar class of VOCs. The major features of the sensor i.e., small size, portability, cost-effectiveness, high sensitivity, and good selectivity, make it a potential candidate for diabetes monitoring. The promising results of the sensor illustrate its potential in diabetes monitoring applications