Association between Vitamin D Receptor Gene Polymorphisms and Breast Cancer Risk: A Meta-Analysis of 39 Studies

<div><p>Background</p><p>The associations between vitamin D receptor (VDR) gene polymorphisms and breast cancer risk were comprehensively investigated to clarify issues that remain controversial.</p><p>Methodology/Principal Findings</p><p>An electronic search was conducted of several databases, including PubMed, the Cochrane library, Web of Science, EMBASE, CBM and CNKI, for papers that describe the association between <i>Fok1,</i> poly-A repeat, <i>Bsm1, Taq1</i> or <i>Apa1</i> polymorphisms of the <i>VDR</i> gene and breast cancer risk. Summary odds ratios and 95% confidence intervals (CI) were estimated based on a fixed-effect model (FEM) or random-effect model (REM), depending on the absence or presence of significant heterogeneity. A total of 39 studies met the inclusion criteria. A meta-analysis of high-quality studies showed that the <i>Fok1</i> polymorphism of the <i>VDR</i> gene was associated with an increased risk of breast cancer (<i>ff</i> vs. <i>Ff</i>+<i>FF</i>, OR: 1.09, 95%CI: 1.02 to 1.16, p = 0.007). No significant associations were observed between the other polymorphisms and breast cancer risk. No positive results were detected by pooling the results of all relevant studies.</p><p>Conclusion</p><p>A meta-analysis of high-quality studies demonstrated that the <i>Fok1</i> polymorphism of the <i>VDR</i> gene was closely associated with breast cancer risk.</p></div

Characteristics of studies included in the meta-analysis of the relation between the Fok1,Poly A, Bsm1,Taq1 and Apa1 polymorphisms in the vitamin D receptor gene and breast cancer.

<p>PCR-RFLP: Polymerase chain restriction fragment length polymorphism.</p

The pooled measures on the relation of Fok1, Poly A, Bsm1, Taq1 and Apa1 polymorphisms with breast cancer.

<p>HWE: Hardy Weinberg Equilibrium.</p><p>P_h:P for heterogeneity, heterogeneity was checked by the chi square based Q test.</p><p>The symbol *shows the positive result.</p

Forest plots of association of <i>Fok1</i> polymorphism with breast cancer.

<p>Significant association was detected between the genotype <i>ff</i> and breast cancer in recessive model (<i>ff</i> vs. <i>Ff</i>+<i>FF</i>). The squares and horizontal lines correspond to OR and 95% CI of specific study, and the area of squares reflects study weight. The diamond represents the pooled OR and 95% CI. Heterogeneity was checked by the chi square based Q test.</p

Begg’s funnel plot to examine publication bias for comparisons of <i>Fok1</i> polymorphism (<i>ff</i> vs. <i>Ff</i>+<i>FF</i>).

<p>Begg’s funnel plot to examine publication bias for comparisons of <i>Fok1</i> polymorphism (<i>ff</i> vs. <i>Ff</i>+<i>FF</i>).</p

Molecular Simulations of Solute Transport in Polymer Melts

Polymer membranes are typically used to separate gas mixtures on the basis of molecular size differences (“sieving”). The gas purity is known to be inversely proportional to the membrane flux, and the slope of this plot in glassy polymers is empirically found to be determined by the sizes of the gas molecules being separated, λ = (<i>d</i>_<i>B</i>/<i>d</i>_<i>A</i>)² – 1. Despite potential mechanistic differences, the separation performance of rubbery polymers is often discussed in the same framework as their glassy counterparts. Here we perform molecular dynamics simulations of spherical solutes in coarse-grained high-density, high temperature polymer melts to gain a molecular understanding of their transport and separation behavior. We find that the diffusion coefficient follows an exponential law <i>D</i> ∼ <i>e</i>^–<i>ad</i>. Since this dependence results in λ = <i>d</i>_<i>B</i>/<i>d</i>_<i>A</i> – 1, these findings do not provide a direct understanding of the experimentally deduced slope of the Robeson plot

Facile synthesis of bisphosphine monoxides from Morita–Baylis–Hillman carbonates

<p>A facile two-step synthesis of bisphosphine monoxides (BPMOs, with both the phosphine and phosphine oxide moieties within one molecule) from readily available Morita–Baylis–Hillman (MBH) carbonates was realized. Under the catalysis of DABCO, the MBH carbonates undergo allylic phosphorylation reaction with diphenylphosphine oxide or diethyl phosphonate to give monophosphine oxides bearing an activated alkene moiety; subsequent base-catalyzed hydrophosphination of the prepared monophosphine oxide with HPPh₂ readily affords the BPMOs.</p

Representative corneal photos after the surgery.

<p>Corneas in the experimental group were clear, and the anterior chamber and the iris were clearly visible at 28 days (a). In contrast, corneas in the control group were opaque (b). Corneas in the experimental group were much thinner than that in the control group and the endothelium surface was also smoother under slit observation at 28 days (c and d). Confocal microscopy confirmed the polygonal cell coverage of the Descemet’s membrane in the experimental group at 28 days and 2 months (e and g), while there was only denuded Descemet’s membrane in the control group at 28 days (f), and there was some newborn CEC at the marginal region at 2 months in the control group (h).</p

Contact-inhibition analysis of CEC-like cells.

<p>(a) HE staining of the reconstructed corneal endothelium showed that CEC-like cells kept a monolayer after 30 days cultivation on APCM in cross section view. (b) Alizarin red S and trypan blue double-staining of the reconstructed endothelium showed the “lake reaction” of cell borders and no multiple layers from plane view. Scale bars: 50 um.</p

Histological examination of the corneas after the surgery.

<p>(a) Cells covering the Descemet’s membrane in the experimental group were CFDA SE-positive under the fluorescence microscope. (b and c) No signal was detected from the corneas of negative control and normal control groups. (d and e) HE-stained cross-section showed similar results that the Descemet’s membrane was covered by a cell monolayer in the experimental group, and no cells were present on Descemet’s membrane in the control group. (f) HE staining of normal rat cornea. (g, h and i) High magnification images of corneal endothelia in d, e and f respectively. Scale bars: 50 µm.</p