Haiyu Wang

Association between X-ray repair cross complementing group 1 codon 399 and 194 polymorphisms and lung cancer risk: A meta-analysis

Genetic variations in DNA repair genes are thought to modify DNA repair capacity and suggested to be related to cancer risk. However, epidemiological results have been inconsistent. In this meta-analysis, we assessed reported studies of association between polymorphisms of X-ray repair cross complementing group 1 (XRCC1) codon 399 and 194, and lung cancer risk. We found decreased lung cancer risk among subjects carrying XRCC1 codon 194 Arg/Trp genotype [odds ratio (OR)=0.88, 95% confidence interval (95% CI): 0.79-0.97], using 4848 cases and 6592 controls from 16 studies. There was no association between lung cancer risk and XRCC1 codon 399 polymorphism in total population, when stratified by source of control, we found a protective effect of the XRCC1 codon 399 Gln/Gln and Arg/Gln or Gln/Gln polymorphisms for lung cancer on the basis of population control (OR=0.73, 95% CI: 0.58-0.92; OR=0.86, 95% CI: 0.77-0.97, respectively). Data indicated that certain XRCC1 codon 399 and 194 variant may affect the susceptibility of lung cancer. Recommendations for further studies include pooling of individual data to facilitate evaluation of multigenic effects and detailed analysis of effect modification by environmental exposure.

Association between CYP2E1 genetic polymorphisms and lung cancer risk: a meta-analysis.

Genetic variations in metabolic genes are thought to modify the metabolic process of carcinogens and are suggested to be related to cancer risk. However, epidemiological results are not always consistent. In this meta-analysis, we assessed reported studies of associations between polymorphisms of CYP2E1 RsaI/PstI and DraI, and the risk of lung cancer. We found decreased lung cancer risk among subjects carrying CYP2E1 RsaI/PstI c1/c2 and c1/c2+c2/c2 genotype [odds ratio (OR)=0.80, 95% confidence interval (CI): 0.72-0.89 and OR=0.82, 95% CI: 0.72-0.93, respectively], using 4436 cases and 6385 controls from 26 studies. We also observed a decreased lung cancer risk among subjects carrying c1/c2 and c1/c2+c2/c2 genotypes in the Asian population and on the basis of population control in stratified analysis. We found a protective effect of the CYP2E1 DraI CC and CD+CC polymorphisms for lung cancer (OR=0.58, 95% CI: 0.41-0.81 and OR=0.84, 95% CI: 0.73-0.96, respectively). The meta-analysis suggests that CYP2E1 RsaI/PstI and DraI polymorphisms may affect the susceptibility of lung cancer, and a study with a larger sample size is needed to further evaluate gene-environment interaction on CYP2E1 polymorphisms and lung cancer risk.

Benzo(a)pyrene promotes A549 cell migration and invasion through up-regulating Twist

Benzo(a)pyrene (BaP) is one of the strongest carcinogens in cigarette smoke, which is an established human carcinogen. Twist, a transcription factor of the basic helix–loop–helix class, is reported to regulate lung cancer metastasis. Evidence has shown that BaP could induce Twist mRNA expression in non-small cell lung cancer (NSCLC) cell line A549 and promote lung adenocarcinoma cell invasion. However, it is unclear whether BaP promotes the migration and invasion of NSCLC cells by Twist modulation. A549 cell was exposed to BaP for different time. MTT assay was applied to assess cell proliferation. Silencing of Twist was done by small interfering RNA. Wound-healing assay was used to evaluate the capability of cell migration. Transwell assay was used to detect the capability of cell invasion. Western blotting and quantitative polymerase chain reaction were used to detect Twist expression. The levels of Twist protein expression and mRNA expression were increased with the treatment of BaP, compared with solvent control. The capability of wound healing of A549 cells was increased in BaP-treated group, compared with solvent control. BaP enhanced the capability of invasion of A549 cells. Twist knockdown could block the migration and invasion of A549 cells induced by BaP treatment. The mRNA levels of Twist were higher in metastatic NSCLC tissue samples than in primary NSCLC tissue samples, and higher levels of Twist mRNA were observed in metastatic NSCLC tissue samples with smoking history than in those with nonsmoking history. BaP treatment could promote the migration and invasion of NSCLC cells by up-regulating Twist expression.

Glutathione S-transferase T1 gene deletion polymorphism and lung cancer risk in Chinese population: A meta-analysis

Genetic variations in metabolic genes are considered to modulate metabolic process of carcinogens and are suggested to be related to cancer risk. However, epidemiological results are not always consistent. In this meta-analysis, we evaluated reported studies of association between polymorphism of glutathione S-transferase T1 gene (GSTT1) and the risk of lung cancer in Chinese population. We found an increased lung cancer risk among subjects carrying GSTT1 null genotype [odds ratio (OR)=1.36, 95 percent confidence interval (95% CI): 1.09-1.69], using 1625 cases and 2188 controls from 11 studies. We also observed an increased risk of lung cancer among null genotype carriers in squamous cell carcinoma and adenocarcinoma, and on the basis of population control in stratified analyses. The meta-analysis suggests that GSTT1 deletion polymorphisms may have an effect on the susceptibility of lung cancer in Chinese population, and a study with the larger sample size is needed to further evaluate gene-gene and gene-environment interaction on GSTT1 deletion polymorphisms and lung cancer risk in Chinese population.

Biomarkers of chromosomal damage in peripheral blood lymphocytes induced by polycyclic aromatic hydrocarbons: a meta-analysis.

BackgroundA crucial early event in polycyclic aromatic hydrocarbons (PAHs) carcinogenesis is the induction of genomic instability phenotype that initiates the progression of a proliferative cell into a cancer cell. However, epidemiological results have been inconsistent.ObjectivesTo assess reported studies of associations between the levels of chromosomal damage including sister chromatid exchange (SCE), chromosomal aberrations (CA), and cytokinesis-block micronucleus (CBMN) in peripheral blood lymphocytes and occupational exposure to PAHs.MethodsMeta-analysis on the association between chromosomal damage and occupational exposure to PAHs was performed with STATA 10.0 software package and Review Manager 4.2.10 in this study.ResultsWe found statistically significant differences in the frequencies of SCE, CBMN, and CA (aberrations per 100 cells) in peripheral blood lymphocytes between PAHs-exposed group and control group, and the summary estimates of weighted mean difference were 1.42 (95% CI: 0.82–2.02), 1.22 (95% CI: 0.33–2.10), and 0.96 (95% CI: 0.37–1.56), respectively.ConclusionsData indicate that the frequencies of SCE, CBMN, and CA (aberrations per 100 cells) in peripheral blood lymphocytes might be indicators of early genetic effects for occupationally PAHs-exposed population.

The Association of GSTM1 Deletion Polymorphism with Lung Cancer Risk in Chinese Population: Evidence from an Updated Meta-analysis

Previous studies have reported the association of glutathione S-transferase M1 (GSTM1) deletion polymorphism with genetic susceptibility of lung cancer in Chinese population. However, the results remained controversial. The aim of this study was to clarify the association of GSTM1 deletion polymorphism with lung cancer risk in Chinese population. Systematic searches were performed through the search engines of Medline/Pubmed, Web of Science, EMBASE, CNKI and Wanfang Medical Online. The pooled effects were calculated by STATA 10.0 software package and Review Manager 5.0.24. Overall, we observed an association of GSTM1 deletion polymorphism with increased lung cancer risk in Chinese population (odds ratio (OR) = 1.46, 95% confidence interval (95%CI): 1.32–1.66 for null genotype vs. present genotype) based on 53 studies including 7,833 cases and 10,353 controls. We also observed an increased risk of GSTM1 null genotype for lung cancer in stratified analyses by source of control, smoking status and histological type. The findings suggest that GSTM1 deletion polymorphism may contribute to lung cancer risk in Chinese population. Further, well-designed studies with larger sample sizes are required to verify the results.

Increased Frequency of Micronuclei in Binucleated Lymphocytes among Occupationally Pesticide-exposed Populations: A Meta- analysis

BACKGROUND The cytokinesis-block micronucleus (CBMN) assay is a standard cytogenetic tool employed to evaluate chromosomal damage subsequent to pesticide exposure. OBJECTIVES To evaluate the pooled levels of total micronuclei (MN) and binucleated cells with micronuclei (MNC) in 1000 binucleated lymphocytes among population occupationally exposed to pesticides and further determine the more sensitive biomarker of CBMN. MATERIALS AND METHODS A meta-analysis on the pooled levels of MN and MNC in binucleated lymphocytes among occupationally pesticide-exposed populations was conducted using STATA 10.0 software and Review Manager 5.0.24 in this study. RESULTS We found significant differences in frequencies of MN and MNC in 1000 binucleated lymphocytes between pesticide-exposed groups and controls, and the summary estimates of weighted mean difference were 6.82 [95% confidence interval (95% CI): 4.86-8.78] and 5.08 (95% CI: 2.93-7.23), respectively. However, when we conducted sensitivity analyses further, only the MN remained statistically different, but not the MNC, the summary estimates of weight mean difference were 2.86 (95% CI: 2.51-3.21) and 0.50 (95% CI: -0.16-1.17), respectively. We also observed pesticide-exposed subjects had significantly higher MN frequencies than controls among smokers and nonsmokers, male and female populations, and American, Asian and European countries in stratified analyses. CONCLUSIONS The frequency of MN in peripheral blood lymphocytes might be a more sensitive indicator of early genetic effects than MNC using the CBMN assay for occupationally pesticide- exposed populations.

An Updated Meta-analysis on the Association of X-Ray Repair Cross Complementing Group 1 Codon 399 Polymorphism with Hepatocellular Carcinoma Risk

BACKGROUND A number of studies have reported the association of X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism with susceptibility to hepatocellular carcinoma (HCC). However, the results were inconsistent and inconclusive. The aim of this study was to comprehensively explore the association of XRCC1 Arg399Gln variant with HCC risk. MATERIALS AND METHODS Systematic searches of PubMed, Elsevier, Science Direct, CNKI and Chinese Biomedical Literature Database were performed. Pooled odds ratio (OR) with 95% confidence intervals (CI) was calculated to estimate the strength of association. RESULTS Overall, we observed an increased HCC risk among subjects carrying XRCC1 codon 399 Gln/Gln, Arg/Gln and Gln/ Gln+Arg/Gln genotypes (OR=1.20, 95%CI: 1.05-1.38, OR=1.16, 95%CI: 1.05-1.28, and OR=1.14, 95%CI: 1.04-1.24, respectively) based on 20 studies including 3374 cases and 4633 controls. In subgroup analysis, we observed an increased risk of XRCC1 codon 399 Gln/Gln, Arg/Gln and Gln/Gln+Arg/Gln polymorphisms for HCC in hospital-based study (OR=1.25, 95%CI: 1.03-1.51, OR=1.21, 95%CI: 1.07-1.36 and OR=1.18, 95%CI: 1.06-1.31, respectively) and in Asian population (OR=1.19, 95%CI: 1.03-1.38, OR=1.17, 95%CI: 1.04-1.30 and OR=1.14, 95%CI: 1.04-1.25, respectively). Limiting the analysis to the studies with controls in agreement with Hardy-Weinberg equilibrium (HWE), we observed an increased HCC risk among Gln/Gln, Arg/Gln and Gln/ Gln+Arg/Gln genotype carriers (OR=1.17, 95%CI: 1.05-1.29, OR=1.12, 95%CI: 1.00-1.25 and OR=1.11, 95%CI: 1.02-1.21, respectively). CONCLUSIONS This updated meta-analysis results suggest that XRCC1 Arg399Gln variants may contribute to HCC risk. Well-designed studies with larger sample size were required to further verify our findings.

Updated meta-analysis of the association between CYP2E1 RsaI/PstI polymorphisms and lung cancer risk in Chinese population.

BACKGROUND A number of studies have reported relationships of CYP2E1 RsaI/PstI polymorphisms with susceptibility to lung cancer in Chinese population. However, the epidemiologic results have been conflictive rather than conclusive. The purpose of this study was to address the associations of CYP2E1 RsaI/PstI polymorphisms with lung cancer risk in Chinese population comprehensively. MATERIALS AND METHODS Systematic searches were conducted in the PubMed, Science Direct, Elsevier, CNKI and Chinese Biomedical Literature Databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of association. RESULTS Overall, we observed a decreased lung cancer risk among subjects carrying CYP2E1 RsaI/PstI c1/ c2 and c1/c2+c2/c2 genotypes (OR=0.76, 95%CI: 0.64-0.90 and OR=0.78, 95%CI: 0.66-0.93, respectively), as compared with subjects carrying the c1/c1 genotype. In subgroup analysis, we observed a decreased lung cancer risk among c1/c2 carriers in hospital-based studies (OR=0.81, 95%CI: 0.68-0.98) and among carriers with c1/ c2 and c1/c2+c2/c2 genotypes in population-based studies(OR=0.57, 95%CI: 0.42-0.79 and OR=0.58, 95%CI: 0.43-0.79, respectively), as compared with subjects carrying the c1/c1 genotype. Limiting the analysis to studies with controls in Hardy-Weinberg equilibrium (HWE), we similarly observed a decreased lung cancer risk among c1/c2 and c1/c2+c2/c2 carriers (OR=0.73, 95%CI: 0.60-0.88 and OR=0.73, 95%CI: 0.60-0.88, respectively), as compared with c1/c1. CONCLUSIONS Our results suggested that CYP2E1 RsaI/PstI c1/c2 and c1/c2+c2/c2 variants might be a protective factor for developing lung cancer in Chinese population. Further well-designed studies with larger sample size are required to verify our findings.

The association between LEPR Q223R polymorphisms and breast cancer risk.

Recently, we have read with great interest the article entitled “The association between polymorphisms in the leptin receptor (LEPR) gene and risk of breast cancer: a systematic review and pooled analysis” published online by Wang et al. (Breast Cancer Res Treat 136:231–239, 2012). This article suggests that the A allele of LEPR gene rs1137101 variant was low-penetrant risk factor for developing breast cancer. The result is encouraging. Nevertheless, several key issues are worth noticing.