GSTM3 A/B Polymorphism and Risk for Head and Neck Cancer: A Meta-Analysis

<div><p>Background</p><p>Glutathione S-transferase M3 (GSTM3) is an important member of the GSTs that plays a critical role in the development of head and neck cancer (HNC). Several studies have investigated between the GSTM3 A/B polymorphism and risk of HNC, however, the results remain controversial. The aim of this meta-analysis is to evaluate the association between the GSTM3 A/B polymorphism and the risk of HNC.</p><p>Methods</p><p>All eligible case-control studies published up to July 2013 were identified by searching PubMed and Web of Science. The HNC risk associated with the GSTM3 A/B polymorphism was estimated for each study by odds ratios (OR) together with its 95% confidence interval (CI), respectively.</p><p>Results</p><p>Fourteen studies from ten publications with 2110 patients and 2259 controls were included. Overall, the GSTM3 A/B polymorphism was associated with a decreased risk of HNC using the dominant model, homozygote comparison model and heterozygote comparison model (OR = 0.82, 95%CI: 0.71–0.94; OR = 0.67, 95%CI: 0.49–0.94; and OR = 0.84, 95%CI: 0.73–0.97, respectively); besides, in stratification analyses by ethnicity, similar results were observed in Caucasian populations. Stratification by tumor site indicated that the GSTM3 polymorphism was associated with a decreased risk of laryngeal cancer under recessive model and homozygote comparison (OR = 0.52, 95%CI: 0.30–0.89; and OR = 0.50, 95%CI: 0.29–0.87, respectively); By stratifying source of control, decreased cancer risk was observed in hospital-based population under all genetic models (OR = 0.67, 95%CI: 0.56–0.81 for the dominant model; OR = 0.66, 95%CI: 0.46–0.95 for the recessive model; OR = 0.55, 95%CI: 0.37–0.83 for the homozygote comparison model, and OR = 0.70, 95%CI: 0.58–0.84 for the heterozygote comparison model).</p><p>Conclusions</p><p>This meta-analysis suggests that the GSTM3 A/B polymorphism may be an important protective factor for HNC, especially of laryngeal cancer and Caucasian populations.</p></div

Characteristics of studies included in the meta-analysis.

<p>¹ PB: population-based,</p><p>² HB: hospital-based,</p><p>³ HWE, Hardy-Weinberg equilibrium; <i>P</i>_HWE was calculated by goodness-of fit χ²-test, <i>P</i>_HWE<0.05 was considered statistically significant,</p><p>⁴ PCR-RFLP, polymerase chain reaction-restriction fragment length polymorphism.</p><p>⁵ NR, not reported.</p

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Characteristics of Studies Included in the Meta-analysis.

<p>AR, allergic rhinitis;AC, allergic conjunctivitis; DNSS, daytime nasal symptoms score; DESS, daytime eye symptoms score; CSS, composite symptoms score; NSS, nighttime symptoms score; RQLQ, rhinoconjunctivitis quality-of-life scores.</p><p>Characteristics of Studies Included in the Meta-analysis.</p

The Efficacy and Safety of Selective H₁-Antihistamine versus Leukotriene Receptor Antagonist for Seasonal Allergic Rhinitis: A Meta-Analysis

<div><p>Background</p><p>Both selective H₁-antihistamine (SAH) and leukotriene receptor antagonist (LTRA) have been shown to be effective in treating patients with seasonal allergic rhinitis (SAR), but it is still uncertain which treatment option is optimal. This meta-analysis was aimed to compare the efficacy and safety of SAH and LTRA for SAR.</p><p>Materials and Methods</p><p>PubMed, EMBASE and the Cochrane Library were searched for all eligible studies that compared the efficacy and safety of SAH and LTRA for SAR up to September 7, 2014. The pooled mean difference (MD), odd ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using a fixed- or random-effects model.</p><p>Results</p><p>Nine studies with 5781 SAR patients were included. The results showed that SAH is superior to LTRA in terms of the daytime eye symptoms score (DESS) and composite symptoms score (CSS) for SAR (MD = 0.06, 95% CI, 0.03 to 0.10, <i>P</i> = 0.000, <i>I</i>² = 99%; MD = 0.03, 95% CI, 0.01 to 0.05, <i>P</i> = 0.010, <i>I</i>² = 98%), whereas LTRA overmatched SAH with respect to the night-time symptoms score (NSS) (MD = −0.04, 95% CI, −0.05 to −0.02, <i>P</i> = 0.000, <i>I</i>² = 97%). Additionally, the results of subgroup analysis indicated that the dose, duration and gender of the patients might impact the comparisons of the effects of SAH and LTRA on their efficacy for SAR.</p><p>Conclusion</p><p>This meta-analysis suggested that SAH and LTRA have similar effects and safety for SAR, but SAH is more appropriate for daytime nasal symptoms (congestion, rhinorrhea, pruritus and sneezing), while LTRA is better suited for nighttime symptoms (difficulty going to sleep, nighttime awakenings, and nasal congestion on awakening), respectively. Meanwhile, the dose, duration and gender of patients may influence the anti-SAR effects of SAH and LTRA.</p></div

Begg's funnel plot for publication bias test. Each point represents an independent study for the indicated association under the dominant model.

<p>Begg's funnel plot for publication bias test. Each point represents an independent study for the indicated association under the dominant model.</p

Flow chart showing study selection procedure.

<p>Flow chart showing study selection procedure.</p

Subgroup analysis by tumor site of ORs with a fixed-effects model for association between GSTM3 polymorphism and HNC risk.

<p>(<b>A</b> recessive model; <b>B</b> BB <i>vs.</i> AA).</p

Forest plot of ORs for association between GSTM3 A/B and risk of HNC.

<p>(<b>A</b> dominant model; <b>B</b> BB <i>vs.</i> AA; <b>C</b> AB <i>vs.</i> AA).</p

Structural and Functional Consequences of Phosphate–Arsenate Substitutions in Selected Nucleotides: DNA, RNA, and ATP

A recent finding of a bacterial strain (GFAJ-1) that can rely on arsenic instead of phosphorus raised the questions of if and how arsenate can replace phosphate in biomolecules that are essential to sustain cell life. Apart from questions related to chemical stability, there are those of the structural and functional consequences of phosphate-arsenate substitutions in vital nucleotides in GFAJ1-like cells. In this study we selected three types of molecules (ATP/ADP as energy source and replication regulation; DNA–protein complexes for DNA replication and transcription initiation; and a tRNA–protein complex and ribosome for protein synthesis) to computationally probe if arsenate nucleotides can retain the structural and functional features of phosphate nucleotides. Hydrolysis of adenosine triarsenate provides 2–3 kcal/mol less energy than ATP hydrolysis. Arsenate DNA/RNA interacts with proteins slightly less strongly than phosphate DNA/RNA, mainly due to the weaker electrostatic interactions of arsenate. We observed that the weaker arsenate RNA–protein interactions may hamper rRNA assembly into a functional ribosome. We further compared the experimental EXAFS spectra of the arsenic bacteria with theoretical EXAFS spectra for arsenate DNA and rRNA. Our results demonstrate that while it is possible that dried GFAJ-1 cells contain linear arsenate DNA, the arsenate 70S ribosome does not contribute to the main arsenate depository in the GFAJ-1 cell. Our study indicates that evolution has optimized the inter-relationship between proteins and DNA/RNA, which requires overall changes at the molecular and systems biology levels when replacing phosphate by arsenate