The SNP rs961253 in 20p12.3 Is Associated with Colorectal Cancer Risk: A Case-Control Study and a Meta-Analysis of the Published Literature

Background: Colorectal cancer (CRC) is the third common cancer and the fourth leading cause of cancer death worldwide. A single nucleotide polymorphism (SNP), rs961253 located in 20p12, was firstly described to be associated with the increased risk of CRC in a genome-wide association study; however, more recent replication studies yielded controversial results. Methodology/Principal Findings: A hospital-based case-control study in a Chinese population was firstly performed, and then a meta-analysis combining the current and previously published studies were conducted to explore the real effect of rs961253 in CRC susceptibility. In the Chinese population including 641 cases and 1037 controls, per-A-allele conferred an OR of 1.60 (95 % CI = 1.26–2.02) under additive model. In the meta-analysis including 29859 cases and 29696 controls, per-Aallele have an OR of 1.13 (95 % CI = 1.09–1.18) under a random-effects model due to heterogeneity (P = 0.019). Nevertheless, the heterogeneity can be totally explained by ethnicity, with the tau 2 reduced to 0 after including ethnicity in metaregression model. In stratified analysis by ethnicity, per-A-allele had ORs of 1.34 (95 % CI = 1.20–1.50) and 1.11 (95% CI = 1.08–1.14) for Asian and European, respectively, without heterogeneity. Modest influence of each study was observed on overall estimate in sensitive analysis, and evident tendency to significant association was seen in cumulative analysis over time, together indicating the robust stability of the current results

A Common SMAD7 Variant Is Associated with Risk of Colorectal Cancer: Evidence from a Case-Control Study and a Meta-Analysis

<div><h3>Background</h3><p>A common genetic variant, rs4939827, located in <em>SMAD7</em>, was identified by two recent genome-wide association (GWA) studies to be strongly associated with the risk of colorectal cancer (CRC). However, the following replication studies yielded conflicting results.</p> <h3>Method and Findings</h3><p>We conducted a case-control study of 641 cases and 1037 controls in a Chinese population and then performed a meta-analysis, integrating our and published data of 34313 cases and 33251 controls, to clarify the relationship between rs4939827 and CRC risk. In our case-control study, the dominant model was significant associated with increased CRC risk [Odds Ratio (OR) = 1.46; 95% confidence interval (95% CI), 1.19–1.80]. The following meta-analysis further confirmed this significant association for all genetic models but with significant between-study heterogeneity (all <em>P</em> for heterogeneity <0.1). By stratified analysis, we revealed that ethnicity, sample size, and tumor sites might constitute the source of heterogeneity. The cumulative analysis suggested that evident tendency to significant association was seen with adding study samples over time; whilst, sensitive analysis showed results before and after removal of each study were similar, indicating the highly stability of the current results.</p> <h3>Conclusion</h3><p>Results from our case-control study and the meta-analysis collectively confirmed the significant association of the variant rs4939827 with increased risk of colorectal cancer. Nevertheless, fine-mapping of the susceptibility loci defined by rs4939287 should be imposed to reveal causal variant.</p> </div

Some Preliminary Results to Eradicate Leukemic Cells in Extracorporeal Circulation by Actuating Doxorubicin-Loaded Nanochains of Fe₃O₄ Nanoparticles

Leukemia is a non-solid cancer which features the malignant proliferation of leukocytes. Excessive leukocytes of lesions in peripheral blood will infiltrate organs, resulting in intumescence and weakening treatment efficiency. In this study, we proposed a novel approach for targeted clearance of the leukocytes in the peripheral blood ex vivo, which employed magnetic nanochains to selectively destroy the leukocytes of the lesions. The nanochains were doxorubicin-loaded nanochains of Fe3O4 nanoparticles which were fabricated by the solvent exchange method combined with magnetic field-directed self-assembly. Firstly, the nanochains were added into the peripheral blood during extracorporeal circulation and subjected to a rotational magnetic field for actuation. The leukocytes of the lesion were then conjugated by the nanochains via folic acid (FA) targeting. Finally, the rotational magnetic field actuated the nanochains to release the drugs and effectively damage the cytomembrane of the leukocytes. This strategy was conceptually shown in vitro (K562 cell line) and the method’s safety was evaluated in a rat model. The preliminary results demonstrate that the nanochains are biocompatible and suitable as drug carriers, showing direct lethal action to the leukemic cells combined with a rotational magnetic field. More importantly to note is that the nanochains can be effectively kept from entry into the body. We believe this extracorporeal circulation-based strategy by activating nanochains magnetically could serve as a potential method for leukemia treatment in the future

The characteristics of the study population.

†<p><i>P</i> value was calculated by the <i>χ²</i> test;</p>‡<p><i>P</i> value was calculated by the <i>t</i> test.</p

Association between rs961253 and colorectal cancer risk in a Chinese population.

<p>Abbreviations: OR, Odds ratio; 95% CI, 95% confidence interval.</p>†<p><i>P</i> value was calculated by the <i>χ²</i> test.</p>‡<p>Data were estimated by multivariate logistic regression model after adjusting for sex and age.</p

Sensitivity analysis of additive model.

<p>Sensitivity analysis of additive model.</p

Meta-analysis of the rs961253 in association with colorectal cancer risk under different genetic models.

<p>Meta-analysis of the rs961253 in association with colorectal cancer risk under different genetic models.</p

The association between rs4939827 and colorectal cancer risk in a Chinese population.

a<p>CC/(CT+TT);</p>b<p>ORs and their corresponding 95% CIs were calculated by multivariate logistic regression model after adjusting for age and sex.</p

Pooled OR with 95% CI for the association between rs4929827 and colorectal cancer risk in the meta-analysis.

<p>Pooled OR with 95% CI for the association between rs4929827 and colorectal cancer risk in the meta-analysis.</p