ABSTRACT
BACKGROUND: The X-ray repair cross-complementing group 3 (XRCC3) is a highly suspected candidate gene for cancer susceptibility, and a large amount studies have examined the association of the rs861539 in XRCC3 (Thr241Met) with lung cancer risk in various populations. However, the results remain inconclusive. METHODS: The electronic database of PubMed, Medline, Embase and CNKI (China National Knowledge Infrastructure) were searched for case-control studies published up to December 05, 2013. A systematic review and meta-analysis was performed to evaluate the relationship between XRCC3 Thr241Met polymorphism and lung cancer risk. Data were extracted and pooled odds ratio (OR) with its 95% confidence intervals (CI) were calculated. RESULTS: Total 21 studies, including 6880 lung cancer cases and 8329 controls, were available for meta-analysis. Overall, our results showed that the XRCC3 Thr241Met polymorphism was not associated with risk of lung cancer in all genetic contrast models (P>0.05). Stratified analyses by ethnicity (Asians, Caucasians and mixed population) showed similar results. Additionally, no evidence of publication bias was observed by using the funnel plot. CONCLUSIONS: There is no clear evidence showing a significant correlation between XRCC3 Thr241Met polymorphism and lung cancer risk in total population and stratified analysis by ethnicity. However, studies assessing the gene-gene interactions should be considered to further estimate this gene variant in lung cancer risk.
Subject(s)
DNA Repair/genetics , DNA-Binding Proteins/genetics , Lung Neoplasms/genetics , Polymorphism, Genetic , Case-Control Studies , Confidence Intervals , Humans , Lung Neoplasms/ethnologyABSTRACT
<p><b>BACKGROUND</b>Hepatocyte growth factor (HGF) treats ischemic disease by promoting arteriogenesis, however, its mechanism of action is not known. The notch signaling pathway plays an important role in neovascularization. The relationship between the proliferation and migration ability of artery endothelial cells and the Dll4-Notch-Hey2 signaling pathway in the process of arteriogenesis was investigated as a mechanism of action of HGF.</p><p><b>METHODS</b>Based on the prophase study cells and supernatant were harvested at the indicated time after human femoral artery endothelial cells (HFAECs) were infected with adenovirus-HGF (Ad-HGF) at 200 pfu/cell. Cells were analyzed for HGF expression and Notch1, Dll4 and Hey2 expression by ELISA and reverse transcription-PCR (RT-PCR). The changes in the proliferation and migration ability of HFAECs were observed by MTT and Transwell migration experiments. Ad-GFP-infected HFAECs were used as control.</p><p><b>RESULTS</b>Compared with the control group the Ad-HGF group's HGF expression was not increased with time, and the induction by HGF of Notch1, Dll4 and Hey2 gene transcription was not enhanced with an increase of HGF. The proliferation ability of Ad-HGF-transduced HFAECs was enhanced and their migration ability was also enhanced in the presence of HGF.</p><p><b>CONCLUSIONS</b>Through activating the Dll4-Notch-Hey2 signaling pathway, HGF indirectly promotes the proliferation and migration ability of cells, so that offspring artery branches are formed.</p>
