Dataset Information

PAI-1 4G/5G polymorphism contributes to cancer susceptibility: evidence from meta-analysis.

ABSTRACT:

Background

The plasminogen activator inhibitor-1 (PAI-1) is expressed in many cancer cell types and allows the modulation of cancer growth, invasion and angiogenesis. To date, studies investigated the association between a functional polymorphism in PAI-1 (4G/5G) and risk of cancer have shown inclusive results.

Methods

A meta-analysis based on 25 case-control studies was performed to address this issue. Odds ratios (OR) with corresponding 95% confidence intervals (CIs) were used to assess the association. The statistical heterogeneity across studies was examined with I(2) test.

Results

Overall, a significant increased risk of cancer was associated with the PAI-1 4G/4G polymorphism for the allele contrast (4G vs. 5G: OR?=?1.10, CI?=?1.03-1.18, I(2)?=?49.5%), the additive genetic model (4G/4G vs. 5G/5G: OR?=?1.21, CI?=?1.06-1.39, I(2)?=?51.9%), the recessive genetic model (4G/4G vs. 4G/5G+5G/5G: OR?=?1.11, CI?=?1.04-1.18, I(2)?=?20.8%). In the subgroup analysis by ethnicity, the results indicated that individuals with 4G/4G genotype had a significantly higher cancer risk among Caucasians (4G/4G vs. 5G/5G: OR?=?1.31, 95%CI?=?1.09-1.59, I(2)?=?59.6%; 4G/4G vs. 4G/5G: OR?=?1.12, 95%CI?=?1.04-1.21, I(2)?=?3.6%; recessive model: OR?=?1.12, 95%CI?=?1.05-1.21, I(2)?=?25.3%).

Conclusions

The results of the present meta-analysis support an association between the PAI-1 4G/5G polymorphism and increasing cancer risk, especially among Caucasians, and those with 4G allele have a high risk to develop colorectal cancer and endometrial cancer.

SUBMITTER: Wang S

PROVIDER: S-EPMC3577655 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

PAI-1 4G/5G polymorphism contributes to cancer susceptibility: evidence from meta-analysis.

Wang Shangqian S Cao Qiang Q Wang Xiaoxiang X Li Bingjie B Tang Min M Yuan Wanqing W Fang Jianzheng J Qian Jian J Qin Chao C Zhang Wei W

PloS one 20130220 2

<h4>Background</h4>The plasminogen activator inhibitor-1 (PAI-1) is expressed in many cancer cell types and allows the modulation of cancer growth, invasion and angiogenesis. To date, studies investigated the association between a functional polymorphism in PAI-1 (4G/5G) and risk of cancer have shown inclusive results.<h4>Methods</h4>A meta-analysis based on 25 case-control studies was performed to address this issue. Odds ratios (OR) with corresponding 95% confidence intervals (CIs) were used t ...[more]

PMID: 23437240

Similar Datasets

Project description:BackgroundVenous thromboembolism (VTE) is a life-threatening cardiovascular syndrome that characterized by the imbalance of hemostasis and thrombosis and the formation of thrombi in the blood vessels. The aim of this study was to elucidate the clinical impact of the PAI-1 4G/5G polymorphism in Chinese patients with VTE.MethodsA total of 169 subjects (89 VTE, 10 hyperbilirubinemia, 10 hyperlipidemia and 60 healthy controls) were recruited at Peking Union Medical College Hospital. The accuracy of the TaqMan-MGB RT-PCR method for detecting F5 G1691A (FVL) and PAI-1 4G/5G polymorphisms was evaluated by using sequencing method as the gold standard. Besides, the association of the PAI-1 4G/5G polymorphism with susceptibility, treatment efficacy and recurrence status of VTE in Chinese population were explored. Eventually, the plasma PAI-1 antigen levels and PAI-1 4G/5G polymorphisms were determined on additional 64 subjects (32 VTE and 32 healthy controls) simultaneously.ResultsThe TaqMan-MGB RT-PCR method was proven to be highly accurate in determining the FVL and PAI-1 4G/5G polymorphisms without interference from bilirubin and lipids in the samples. No obvious correlation of the PAI-1 4G/5G polymorphism with VTE was observed in our study by using five genetic models (allele, genotype, dominant, recessive and additive). Additionally, we also observed that individuals with the 4G/5G genotype had lower neutrophil counts and neutrophil-to-lymphocyte ratio (NLR) than the 5G/5G genotype. Furthermore, we found that the patients with the 5G/5G genotype were more likely to achieve complete recanalization compared to the 4G/4G genotype. In addition, individuals carrying the 5G/5G genotype were more likely to develop a recurrence-free status as compared to individuals with the 4G/4G or 4G/5G genotypes. PAI-1 antigen levels in the VTE group were significantly higher than those in the HC group. However, there was no significant difference in the antigen levels of PAI-1 among subjects carrying various genotypes in the VTE group or HC group.ConclusionThe PAI-1 4G/5G polymorphism has potential value in assessing the prognosis of Chinese patients with VTE. Our study has laid the foundation for the application of PAI-1 4G/5G polymorphism in the personalized management and monitoring of patients with VTE.

Project description:BackgroundA number of studies were carried out to assess the association of angiotensin I converting enzyme (ACE) I/D and plasminogen activator inhibitor-1 (PAI-1-1) 4G/5G polymorphisms with susceptibility to type 2 diabetes mellitus (T2DM). However, there are a few studies in Iranian patients with T2DM. Here, we tested for an association of ACE I/D and PAI-1 4G/5G polymorphisms with T2DM risk.MethodsOne hundred-eighteen patients with T2DM and 125 healthy subjects were participates in this study. The ACE I/D (rs4340) and PAI-1 4G/5G (rs1799889) polymorphisms was genotyped by conventional and PCR-RFLP assays, receptively. The associations was evaluated by calculating the odds ratio (OR) and 95% confidence interval (95% CI).ResultsThe genotype distribution of ACE I/D and PAI-1 4G/5G polymorphisms were not deviated from the Hardy-Weinberg equilibrium in healthy controls. The ACE II, ID, and DD genotype frequencies were 18.6%, 48.3%, and 33.1% in the T2DM patients versus 24.0%, 45.6% and 30.4% in healthy subjects, respectively. The PAI-1 4G/4G, 4G/5G, and 5G/5G genotype frequencies were 16.9%, 51.7%, and 31.4% in cases versus 24.8%, 57.6% and 17.6% in controls, respectively. There is a significant distribution in genotype/allele of PAI-1 4G/4G between cases with T2DM and healthy control, but not for ACE I/D. Moreover, the 5G/5G genotype is significantly (OR = 2.139, CI 95% 1.171-3.907, p = 0.013) increased the risk of T2DM by two folds in the cases than healthy controls.ConclusionsOur findings suggest that PAI-1 4G/5G may be likelihood risk factor for the development of T2DM in the Iranian patients. The higher frequency of PAI-1 5G/5G genotype in patients with T2DM revealed that individuals with the 5G allele may be at higher risk of T2DM development than those with 4G. However, there was no significant association between ACE I/D polymorphism and T2DM in our population. Future rigorous, well-designed studies with larger sample should replicate this study to confirm our findings in Iranian T2DM patients.

Dataset Information

PAI-1 4G/5G polymorphism contributes to cancer susceptibility: evidence from meta-analysis.

Background

Methods

Results

Conclusions

Publications

PAI-1 4G/5G polymorphism contributes to cancer susceptibility: evidence from meta-analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets