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.

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.

An updated meta-analysis on the association of TGF-ß1 gene promoter -509C/T polymorphism with colorectal cancer risk.

AIM: Published data on the association between transforming growth factor-ß1 (TGF-ß1) gene promoter-509C/T polymorphism and colorectal cancer (CRC) risk are inconsistent and inconclusive. To derive a more precise estimation of this association, a meta-analysis was carried out. METHODS: Meta-analysis was performed to evaluate reported studies of the relationship between TGF-ß1 gene promoter-509C/T polymorphism and colorectal cancer risk using fixed-effects model and random-effects model. RESULTS: We observed an increased colorectal cancer risk among subjects carrying TGF-ß1 gene promoter-509CC+CT genotype (odds ratio (OR)=1.18%, 95% confidence interval (95% CI): 1.06-1.32) using 4440/6785 cases/controls in total population. We observed an increased risk of the TGF-ß1 gene promoter -509CC, CT and CC+CT polymorphisms for colorectal cancer in population-based study (OR=1.36, 95% CI: 1.19-1.56, OR=1.18, 95% CI: 1.03-1.34 and OR=1.26, 95% CI: 1.12-1.43, respectively) in stratified analysis. We observed an increased colorectal risk among CC and CC+CT carriers in European and American population (OR=1.22, 95% CI: 1.04-1.43 and OR=1.18, 95% CI: 1.02-1.38, respectively). We also observed an increased risk of colon cancer among subjects carrying CC+CT genotype (OR=1.31, 95% CI: 1.05-1.63). CONCLUSIONS: The present meta-analysis results suggest that TGF-ß1 gene promoter -509C allele variant is a possible risk factor for developing colorectal cancer. Recommendations for further studies include pooling of individual data to verify results from the study and to facilitate evaluation of multigenic effects and detailed analysis of effect modification by environmental and lifestyle factors.

E-cadherin (CDH1) gene promoter polymorphism and the risk of colorectal cancer : a meta-analysis.

OBJECTIVE: Published data on the relationship between E-cadherin (CDH1) gene promoter polymorphisms and colorectal cancer (CRC) risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was carried out. METHODS: In this meta-analysis, we evaluated reported studies of associations between polymorphisms of CDH1 gene promoter -160 C > A and -347 G > GA site, and CRC risk using fixed-effects model and random-effects model. RESULTS: We found decreased CRC risk among subjects carrying CDH1 -160AA (odds ratio [OR] = 0.86, 95 percent confidence interval [95% CI]: 0.75-0.98) and CA + AA (OR = 0.92, 95% CI: 0.87-0.98), using 4,652/4,428 cases/controls and 7,866/7,689 cases/controls from ten studies, respectively. We found a protective effect of the CDH1 -160CA + AA polymorphisms for CRC in distal site tumor population and population-based control in stratified analysis. We found a protective effect of the CDH1 -160AA and CA + AA polymorphisms for CRC in European and American population (OR = 0.87, 95% CI: 0.76-0.99 and OR = 0.91, 95% CI: 0.85-0.98, respectively). We observed that the CDH1 -347 G/GA + GA/GA carrier had an increased risk of CRC, the summary OR was 1.33 (95% CI: 1.08-1.62). CONCLUSIONS: Data indicated that certain CDH1 gene promoter -160 C > A and -347 G > GA variants might affect the susceptibility of CRC. Recommendations for further studies include pooling of individual data to facilitate evaluation of multigenic effects and detailed analysis of effect modification by environmental and lifestyle factors.

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

BACKGROUND: A 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. OBJECTIVES: To 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. METHODS: Meta-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. RESULTS: We 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. CONCLUSIONS: Data 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.