A study of performance evaluation of cobas e 801 infectious diseases panel.

BACKGROUND: Infectious diseases, such as HCV infection, HBV infection and syphilis, put a huge burden on public health. Accurate and fast testing is required for clinical usage. OBJECTIVES: This study aimed to evaluate the clinical performance of Elecsys® Anti-HCV II, Elecsys® HBsAg II and Elecsys® Syphilis using samples from routine diagnosis in China. METHODS: Specificity was tested in approximately 3000 unselected pseudonymized samples from routine clinical patients for each assay. Sensitivity of HCV and HBsAg assays was tested in 2 seroconversion panels, respectively. RESULTS: The 3 investigational assays on cobas e 801 were showed to have excellent sensitivity and specificity which is comparable to existing assays. CONCLUSION: They are suitable for routine clinical diagnostic use, including pre-operative assessment in China.

The miR-5694/AF9/Snail Axis Provides Metastatic Advantages and a Therapeutic Target in Basal-like Breast Cancer.

Epigenetic deregulation, especially mutagenesis or the abnormal expression of epigenetic regulatory factors (ERFs), plays an important role in malignant tumorigenesis. To screen natural inhibitors of breast cancer metastasis, we adopted small interfering RNAs (siRNAs) to transiently knock down 591 ERF-coding genes in luminal breast cancer MCF-7 cells and found that depletion of AF9 significantly promoted MCF-7 cell invasion and migration. A mouse model of metastasis further confirmed the suppressive role of AF9 in breast cancer metastasis. RNA profiling revealed enrichment of AF9 targets genes in the epithelial-mesenchymal transition (EMT). Mechanistically, tandem mass spectrometry showed that AF9 interacts with Snail, which hampers Snail transcriptional activity in basal-like breast cancer (BLBC) cells. AF9 reconstitutes an activated state on the promoter of Snail, which is a master regulator of EMT, and derepresses genes by recruiting CBP or GCN5. Additionally, microRNA-5694 (miR-5694) targeted and degraded AF9 messenger RNA (mRNA) in BLBC cells, further enhancing cell invasion and migration. Notably, AF9 and miR-5694 expression in BLBC clinical samples correlated inversely. Hence, miR-5694 mediates downregulation of AF9 and provides metastatic advantages in BLBC. Restoring expression of the metastasis suppressor AF9 is a possible therapeutic strategy against metastatic breast cancer.

Association Between LOX-1, LAL, and ACAT1 Gene Single Nucleotide Polymorphisms and Carotid Plaque in a Northern Chinese Population.

Objective: Carotid atherosclerosis is one of the major risk factors for ischemic stroke. The presence of carotid plaque has been widely used to assess the risk of clinical atherosclerotic disease. Lectin-type oxidized LDL (low-density lipoprotein) receptor 1 (LOX-1), lysosomal acid lipase (LAL), and acyl-CoA:cholesterol acyltransferase 1 (ACAT1) are important for lipid accumulation in atherosclerosis. The objective of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) in the LOX-1, LAL, and ACAT1 genes and the presence of carotid plaque in a Northern Chinese population. Methods: Three polymorphisms in LOX-1 (rs1050286), LAL (rs11203042), and ACAT1 (rs11576517) were identified and genotyped in 215 patients with carotid plaque and 252 controls using the polymerase chain reaction with high-resolution melting analysis. Results: The LOX-1 (rs1050286) AA and LAL (rs11203042) TT genotypes were significantly associated with increased risk of carotid plaque, whereas a ACAT1 (rs11576517) TT genotype was shown to be protective against carotid plaque in a Northern Chinese population (p < 0.05). Even after the Bonferroni correction, the LAL (rs11203042) TT genotype (odds ratio = 3.838, 95% confidence interval = 1.748-8.426, p < 0.001) was still associated with an increased risk for carotid plaque. Conclusions: These results suggest that the LAL (rs11203042) TT genotype is associated with increased risk for carotid plaque in a Northern Chinese population, and that the LOX-1 (rs1050286) AA genotype shows a nonstatistically significant trend towards association. However, no association was found between the ACAT1 (rs11576517) polymorphisms and carotid plaque presence.

Association between CLEC4E gene polymorphism of mincle and pulmonary tuberculosis infection in a northern Chinese population.

BACKGROUND: Pulmonary tuberculosis caused by an intracellular pathogen, Mycobacterium tuberculosis continues to exist as a hazardous disease to human life globally. Genetic polymorphisms regulate resistance and susceptibility to tuberculosis. The C-type lectin receptor of family 4 member E (CLEC4E) confers protection against tuberculosis in laboratory animals but its function in influencing exposure or resistance to pulmonary tuberculosis (PTB) in humans remains obscure. AIM: We conducted this research to analyze the effects or concomitance of CLEC4E gene variations with susceptibility to pulmonary tuberculosis in a northern Chinese population. METHOD: In this study, 202 participants with pulmonary tuberculosis and 214 controls without PTB were enrolled. Two single nucleotide polymorphisms (SNPs) for CLEC4E on chromosome 12 were selected with a minor allele frequency of >0.05. All the SNPs were genotyped using high resolution melting analysis-PCR. RESULTS: We estimated and compared two SNPs, rs10841845 and rs10841847. From our study findings, CLEC4E rs10841845 conferred protection against the development of pulmonary TB with a P value of <0.05 and odds ratio of <1 for all models of genetic inheritance. CLEC4E rs10841847 genotypes in co-dominant, Recessive, Dominant models and alleles had a significant statistical difference between patients and controls associated with resistance against the development of PTB (P<0.05 and OR<1). CONCLUSION: Our findings suggest that variations at rs10841845 and rs10841847 of CLEC4E genes are associated with increased individual protection against PTB.

Evaluation of the relationship between CD36 and MARCO single-nucleotide polymorphisms and susceptibility to carotid atherosclerosis in a Chinese Han population.

OBJECTIVE: This study analyzed the genetic association between two scavenger receptors single nucleotide polymorphisms (CD36 rs1761667, MARCO rs12998782) and carotid atherosclerosis in a Chinese Han population. METHODS: Samples of genomic DNA collected from patients (n=215) and healthy control subjects (n=252) were analyzed by the polymerase chain reaction with high-resolution melting analysis. Odds ratios and 95% confidence intervals were used to evaluate the association between the two SNPs and carotid atherosclerosis. RESULTS: There was no difference between the SNPs regarding their association with the frequency of carotid atherosclerosis in the case and control groups or in the male case group and control group. Female patients of genotype GA for CD36 rs1761667 and CT for MARCO rs12998782 were at an increased risk for carotid atherosclerosis. The presence of rs1761667 GA and rs12998782 CT may increase the risk for carotid atherosclerosis among postmenopausal females. CONCLUSIONS: CD36 and MARCO are associated with the susceptibility of Chinese Han females to carotid atherosclerosis. Menopausal status may affect the association between gene polymorphisms and carotid atherosclerosis in the female Chinese Han population.

Evaluation of the relationship between MARCO and CD36 single-nucleotide polymorphisms and susceptibility to pulmonary tuberculosis in a Chinese Han population.

BACKGROUND: Gene polymorphisms impact greatly on a person's susceptibility to pulmonary tuberculosis (PTB). Macrophage receptor with collagenous structure (MARCO) and CD36 are two scavenger receptors (SRs) that can recognize Mycobacterium tuberculosis (Mtb) and play a key role in tuberculosis infection. Gene polymorphisms of MARCO and CD36 may contribute to tuberculosis risk. METHODS: To investigate whether genetic polymorphisms of MARCO and CD36 are associated with susceptibility to PTB, genomic DNA samples from patients (n = 202) and healthy controls (n = 216) were collected and analyzed by polymerase chain reaction with high-resolution melting analysis. RESULTS: We studied two single nucleotide polymorphisms (SNPs) in MARCO (rs12998782 and rs17009726) and three SNPs in CD36 (rs1194182, rs3211956 and rs10499859). Rs12998782 (P = 0.018) might be associated with susceptibility to PTB. Rs1194182 (P < 0.01) and rs10499859 (P < 0.001) might be associated with resistance to PTB. Rs17009726 and rs3211956 were not associated with susceptibility/resistance to PTB. CONCLUSIONS: These data showed that MARCO rs12998782 may increase PTB risk while two SNPs of CD36, rs1194182 and rs10499859 may reduce the risk, indicating MARCO and CD36 as important receptors in response to PTB.

Lentivirus-mediated knockdown of NLK inhibits small-cell lung cancer growth and metastasis.

Nemo-like kinase (NLK), an evolutionarily conserved serine/threonine kinase, has been recognized as a critical regulator of various cancers. In this study, we investigated the role of NLK in human small-cell lung cancer (SCLC), which is the most aggressive form of lung cancer. NLK expression was evaluated by quantitative real-time polymerase chain reaction in 20 paired fresh SCLC tissue samples and found to be noticeably elevated in tumor tissues. Lentivirus-mediated RNAi efficiently suppressed NLK expression in NCI-H446 cells, resulting in a significant reduction in cell viability and proliferation in vitro. Moreover, knockdown of NLK led to cell cycle arrest at the S-phase via suppression of Cyclin A, CDK2, and CDC25A, which could contribute to cell growth inhibition. Furthermore, knockdown of NLK decreased the migration of NCI-H446 cells and downregulated matrix metalloproteinase 9. Treatment with NLK short hairpin RNA significantly reduced SCLC tumor growth in vivo. In conclusion, this study suggests that NLK plays an important role in the growth and metastasis of SCLC and may serve as a potential therapeutic target for the treatment of SCLC.

The association between a novel polymorphism (rs1062577) in ESR1 and breast cancer susceptibility in the Han Chinese women.

OBJECTIVE: The aim of the present study was to analyze the genetic association between the three estrogen receptor 1 (ESR1) single nucleotide polymorphisms (SNPs; rs1062577, rs2881766, and rs9479118) and breast cancer risk in Han Chinese women. METHODS/MATERIALS: To investigate the possible association of genetic polymorphisms of any of the three ESR1 SNPs in breast cancer patients (n = 198) and healthy controls (n = 218) collected from the college hospital, peripheral blood mononuclear cells samples were analyzed by high-resolution melt-polymerase chain reaction. Odds ratios and 95% confidence intervals were used to evaluate the association between the ESR1 SNPs and breast cancer. RESULTS: Patients genotyped AA for ESR1 rs1062577 showed increased breast cancer risk (p = 0.005). In the menarche at ≤ 13-year-old group, there were significant differences in alleles A versus T at rs1062577 and alleles G versus T at rs2881766 between the breast cancer group and the control group. In the > 13-year-old group, the AA genotype at rs1062577, the GG genotype at rs2881766, and the CC genotype at rs9479118 increased breast cancer susceptibility. CONCLUSIONS: These results showed that the ESR1 rs1062577 polymorphism increased breast cancer risk in Han Chinese women, which might be used as a new SNP marker.

F-box protein FBXO22 mediates polyubiquitination and degradation of KLF4 to promote hepatocellular carcinoma progression.

Kruppel-like factor 4 (KLF4), a member of the KLF family of transcription factors, has been considered as a crucial tumor suppressor in hepatocellular carcinoma (HCC). Using affinity purifications and mass spectrometry, we identified FBXO22, Cullin1 and SKP1 as interacting proteins of KLF4. We demonstrate that F-box only protein 22 (FBXO22) interacts with and thereby destabilizes KLF4 via polyubiquitination. As a result, FBXO22 could promote HCC cells proliferation both in vitro and in vivo. However, KLF4 deficiency largely blocked the proliferative roles of FBXO22. Importantly, FBXO22 expression was markedly increased in human HCC tissues, which was correlated with down-regulation of KLF4. Therefore, our results suggest that FBXO22 might be a major regulator of HCC development through direct degradation of KLF4.

CD81 and CLDN1 polymorphisms and hepatitis C virus infection susceptibility: a case control study.

CD81 and CLDN1 interact to form a CD81-CLDN1 co-receptor complex that is crucial in hepatitis C virus (HCV) entry. Variations in the two genes were shown to influence immunological functions; therefore, we hypothesized that polymorphisms in these genes may contribute to HCV susceptibility. A case-control study consisting of 461 patients and 461 controls was conducted to explore the associations between CD81 rs708564 and CLDN1 rs893051 and HCV susceptibility in a Chinese population. We found a decreased HCV risk associated with the CD81 rs708564 TT (odds ratio (OR) = 0.66, 95% CI = 0.44-0.98) genotype. The gene-gene interaction between CD81 and CLDN1 polymorphisms also decreased HCV risk in a joint multiplicative manner (OR for the presence of both CD81 rs708564 TT and CLDN1 rs893051 GG genotypes = 0.59, 95% CI = 0.36-0.97). Furthermore, the CD81 rs708564 TT genotype conferred a more pronounced decrease in HCV susceptibility in combination with lower levels of high-density lipoprotein cholesterol (HDL-C; OR = 0.71, 95% CI = 0.52-0.96), and higher levels of low-density lipoprotein cholesterol (OR = 0.24, 95% CI = 0.09-0.65). We also observed a decreased HCV susceptibility in individuals with higher HDL-C levels who carried the CLDN1 rs893051 G/C genotype. These findings suggest that homozygous CD81 rs708564 TT may be a genetic modifier for avoiding HCV infection whether as a sole single nucleotide polymorphism or combined with the CLDN1 rs893051 GG genotype, and this effect is associated with serum levels of lipoprotein.

Association between the epidermal growth factor 61*A/G polymorphism and hepatocellular carcinoma risk: a meta-analysis.

The epidermal growth factor (EGF) may play a pathological role in hepatocellular carcinoma (HCC). However, the conclusions of published reports on the relationship between the EGF 61*A/G polymorphism and HCC risk remain controversial. To derive a more precise estimation we performed a meta-analysis based on 14 studies that together included 2,506 cases and 4,386 controls. PubMed, EMBASE, Web of Knowledge and the Chinese National Knowledge Infrastructure (CNKI) databases were used to retrieve articles up to August 1, 2014. The crude odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated to evaluate the association. Meta-analysis results showed a significant association between the EGF 61*A/G polymorphism and HCC risk in all four genetic models (allele model: OR=1.25, 95%CI=1.12-1.40; dominant model: OR=1.32, 95%CI=1.14-1.54; recessive model: OR=1.33, 95%CI=1.12-1.58; homozygous model: OR=1.59, 95%CI=1.33- 1.90). Moreover, significant associations were observed when stratified by ethnicity, source of controls, etiology and genotype methods. Thus, this meta-analysis suggests that the G-allele of the EGF 61*A/G polymorphism is associated with an increased risk of HCC, especially in Asians and Caucasians, without influence from the source of controls or etiological diversity. Further studies with larger population sizes are needed to confirm these results.

Correlation of IL-1F genetic polymorphisms with the risk of colorectal cancer among Chinese populations.

Inflammatory/immune cells have the power of infiltrating almost all human solid tumors and influencing all stages of carcinogenesis because of their stimulation of various cytokine subsets. This study aims to determine the correlation of single nucleotide polymorphisms in the IL-17F gene and the risk of colorectal cancer (CRC). One thousand patients diagnosed with CRC and a control group of 354 healthy controls were involved. Peripheral blood samples were collected. The PCR-RFLP method was used to detect the 7383A>G (rs2397084) and 7488T>C (rs763780) in the IL-17F gene. Statistical analyses were conducted with version 12.0 STATA statistical software. We found that the allele model suggested that patients carrying C allele were 1.67 times more likely to develop CRC than healthy controls (odds ratio (OR) = 1.67, 95% confidence interval (CI) = 1.22-2.27, P = 0.001). Similarly, the homozygous and dominant models also revealed that the minor IL-17F 7488C allele conferred an increased CRC risk compared to the major T allele among our study participants (CC vs. TT: OR = 4.15, 95% CI = 1.26-13.36, P = 0.011; TC+CC vs. TT: OR = 1.46, 95% CI = 1.04-2.05, P = 0.027). However, all genetic models indicated that the IL-17F 7383A>G (rs2397084) polymorphism was not associated with CRC risk (all P > 0.05). The results of this study indicate that the 7488T>C (rs763780) in the IL-17F gene may be correlated with increased risk of CRC.

Lack of association between UCHL1 S18Y gene polymorphism and Parkinson's disease in the Asian population: a meta-analysis.

Although many case-control studies have investigated the association between a single UCHL1 S18Y gene polymorphism and the risk of Parkinson's disease (PD), the results have been ambiguous. To evaluate the overall effect between published case-control studies of Asian subjects, we conducted a meta-analysis based on 11 studies including 3,971 PD cases and 3,721 controls. Studies carried out up to 30 April 2014, were identified using the databases PubMed, MEDLINE, EMBASE and Web of Knowledge. The crude odds ratios (ORs) with 95 % confidence intervals (95 % CI) were calculated to evaluate the association. The results of our meta-analysis indicated that the UCHL1 S18Y gene polymorphism does not correlate with the risk of PD (allele model: OR 0.93, 95 % CI 0.84-1.02; dominant model: OR 0.94, 95 % CI 0.86-1.04; recessive model: OR 0.90, 95 % CI 0.77-1.06; homozygous model: OR 0.86, 95 % CI 0.71-1.04). A similar result was observed in subgroup analysis of ethnicity, age at onset, genotype methods, Hardy-Weinberg equilibrium, and source of controls. Thus, the current meta-analysis suggests no evidence for the association between the UCHL1 S18Y polymorphism and PD risk in the Asian population, especially in subgroups of ethnicity and age at onset. Further studies with larger population sizes are needed to confirm this result.

Association between the tumor necrosis factor alpha gene -308G> A polymorphism and the risk of breast cancer: a meta-analysis.

The multifunctional cytokine tumor necrosis factor alpha (TNF-α) plays an important role in cell proliferation, differentiation, apoptosis, lipid metabolism, and endothelial function. To date, many studies have evaluated the association between the TNF-α -308G> A polymorphism and breast cancer risk; however, the results remain ambiguous and inconclusive. To derive a more precise estimation of the association and assess its strength, we carried out a meta-analysis of 20 published case-control studies with 12,360 cases and 15,110 controls using crude odd ratios (ORs) with 95 % confidence intervals (CIs). Overall, no significant associations were found for all genetic models (allele model OR = 1.06, 95 % CI 0.90-1.24, P heterogeneity < 0.001; homozygous model OR = 1.25, 95 % CI 0.85-1.82, P heterogeneity < 0.001; recessive model OR = 1.26, 95 % CI 0.88-1.82, P heterogeneity = 0.001; dominant model OR = 1.00, 95 % CI 0.85-1.18, P heterogeneity < 0.001). Moreover, no significant associations were observed when stratified by ethnicity, control source, genotyping method, or Hardy-Weinberg equilibrium status. However, in the menopausal status subgroup, significantly decreased breast cancer risks were found among postmenopausal women (allele model OR = 0.90, 95 % CI 0.83-0.98; dominant model OR = 0.89, 95 % CI 0.81-0.98), while the TNF-α -308 AA genotype was a breast cancer risk factor in premenopausal women (homozygous model OR = 4.38, 95 % CI 1.44-13.36; recessive model OR = 4.43, 95 % CI 1.47-13.42). This meta-analysis indicated that the TNF-α -308G> A polymorphism is not associated with breast cancer risk in the overall population but that the A allele may be a protective factor for breast cancer in postmenopausal women, and the AA genotype may be a breast cancer risk factor in premenopausal women.

Evaluation of the relationship between IL28B, IL10RB and IL28RA single-nucleotide polymorphisms and susceptibility to hepatitis C virus in Chinese Han population.

Hepatitis C virus (HCV) infection is associated with both viral and host factors. Cytokines, such as interferon (IFN)-λ, play a critical role in modulating the innate and adaptive immune systems. This study aims to investigate the association between single-nucleotide polymorphisms (SNPs) of interleukin (IL) 28B, IL10RB, and IL28RA genes and susceptibility to HCV infection in a population from the Liaoning Province of China. We used high resolution melt-polymerase chain reaction (HRM-PCR) analyses for genotype 6 polymorphisms in these genes in 271 chronic HCV-infected patients and in 300 healthy control subjects. The distribution of IL10RB and IL28RA genotypes among the HCV-infected and control groups did not differ significantly. However, we did find that the four IL28B variants were in complete linkage disequilibrium (r(2) = 0.831-0.922), and the frequency of rs8099917 GT genotype was significantly higher among chronic HCV-infected patients than among controls (OR = 2.21, 95% CI = 1.33-3.68, P = 0.00193); the G allele was found more frequently in the chronic HCV-infected group than in the control group (OR = 2.10, 95% CI = 1.28-3.44, P = 0.00276). Haplotype analysis showed that IL28B (rs12980275, rs11881222, rs12979860 and rs8099917) haplotype AACT had a protective effect for HCV infection (OR = 0.52, 95% CI = 0.33-0.83, P = 0.00551). This study indicates that the four SNPs in IL28B are correlated with susceptibility to HCV infection.

Association between XRCC5, 6 and 7 gene polymorphisms and the risk of breast cancer: a HuGE review and meta-analysis.

OBJECTIVE: Non-homologous end joining (NHEJ) is a pathway for repairing DNA double-strand breaks. Recent publications indicated that XRCC5, XRCC6 and XRCC7 genes may participate in the pathogenesis of breast cancer. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to investigate associations between XRCC5, XRCC6 and XRCC7 genetic polymorphisms in the NHEJ pathway and breast cancer risk. METHODS: Studies focusing on the relationship between genetic polymorphisms in XRCC5, XRCC6 and XRCC7 genes and susceptibility to breast cancer were selected from the Pubmed, Cochrane library, Embase, Web of Science, Springerlink, CNKI and CBM databases. Data were extracted by two independent reviewers. The meta-analysis was performed with Review Manager Version 5.1.6 and STATA Version 12.0 software. The odds ratio (OR) with 95% confidence interval (95%CI) was calculated based on the extracted data. RESULTS: According to the inclusion criteria, we final included seven studies with a total of 2,864 breast cancer cases and 3,060 healthy controls. Meta-analysis results showed that rs3835 (G>A) and rs828907 (G>T) in XRCC5 gene, and rs132793 (G>A) in XRCC6 gene might increase the risk of breast cancer, while rs132788 G>T and rs6002421 (A>G) might be protective factors. However, there was no relationship between XRCC7 genetic polymorphisms and the risk of breast cancer. CONCLUSION: This meta-analysis suggests that the rs3835 G>A and rs828907 G>T in XRCC5 gene, rs6002421 (A>G), rs132788 (G>T) and rs132793 (G>A) in XRCC6 gene might be risk factors for breast cancer, while the rs132788 (G>T) and rs6002421 (A>G) in XRCC6 gene might be protective.

Genetic variants of CYP2D6 gene and cancer risk: a HuGE systematic review and meta-analysis.

OBJECTIVE: Genetic polymorphisms in metabolic enzymes are associated with numerous cancers. A large number of single nucleotide polymorphisms (SNPs) in the CYP2D6 gene have been reported to associate with cancer susceptibility. However, the results are controversial. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to summarize the evidence for associations. METHODS: Studies focusing on the relationship between CYP2D6 gene polymorphisms and susceptibility to cancer were selected from the Pubmed, Cochrane library, Embase, Web of Science, Springerlink, CNKI and CBM databases. Data were extracted by two independent reviewers and the meta-analysis was performed with Review Manager Version 5.1.6 and STATA Version 12.0 software. Odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated. RESULTS: According to the inclusion criteria, forty-three studies with a total of 7,009 cancer cases and 9,646 healthy controls, were included in the meta-analysis. The results showed that there was a positive association between heterozygote (GC) of rs1135840 and cancer risk (OR=1.92, 95%CI: 1.14-3.21, P=0.01). In addition, we found that homozygote (CC) of rs1135840 might be a protective factor for cancer (OR=0.58, 95%CI: 0.34-0.97, P=0.04). Similarly, the G allele and G carrier (AG + GG) of rs16947 and heterozygote (A/del) of rs35742686 had negative associations with cancer risk (OR=0.69, 95%CI: 0.48-0.99, P=0.04; OR=0.60, 95%CI: 0.38-0.94, P=0.03; OR=0.50, 95%CI: 0.26-0.95, P=0.03; respectively). CONCLUSION: This meta-analysis suggests that CYP2D6 gene polymorphisms are involved in the pathogenesis of various cancers. The heterozygote (GC) of rs1135840 in CYP2D6 gene might increase the risk while the homozygote (CC) of rs1135840, G allele and G carrier (AG + GG) of rs16947 and heterozygote (A/del) of rs35742686 might be protective factors.

Lack of association between LIG4 gene polymorphisms and the risk of breast cancer: a HuGE review and meta-analysis.

OBJECTIVE: Non-homologous end joining (NHEJ) is one of the pathways of repair of DNA double-strand breaks. A number of genes involved in NHEJ have been implicated as breast cancer susceptibility genes such as LIG4. However, some studies have generated conflicting results. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to investigate association between LIG4 gene polymorphisms in the NHEJ pathway and breast cancer risk. METHODS: Studies focusing on the relationship between LIG4 gene polymorphisms and susceptibility to breast cancer were selected from the Pubmed, Cochrane library, Embase, Web of Science, Springerlink, CNKI and CBM databases. Data were extracted by two independent reviewers and the meta-analysis was performed with Review Manager Version 5.1.6 and STATA Version 12.0 software, calculating odds ratios (ORs) with 95% confidence intervals (95%CIs). RESULTS: According to the inclusion criteria, we final included seven studies with a total of 10,321 breast cancer cases and 10,160 healthy controls in the meta-analysis. The results showed no association between LIG4 gene polymorphisms (rs1805386 T>C, rs1805389 C>T, rs1805388 C>T and rs2232641 A>G) and breast cancer risk, suggesting that the mutant situation of these SNPs neither increased nor decreased the risk for breast cancer. In the subgroup analysis by Hardy-Weinberg equilibrium (HWE) and ethnicity, we also found no associations between the variants of LIG4 gene and breast cancer risk among HWE, non-HWE, Caucasians, Asians and Africans. CONCLUSION: This meta-analysis suggests that there is a lack of any association between LIG4 gene polymorphisms and the risk of breast cancer.

Association of functional polymorphisms of the XRCC4 gene with the risk of breast cancer: a meta-analysis.

OBJECTIVE: X-ray cross-complementing group 4 (XRCC4) is a major repair gene for DNA double-strand breaks (DSB) in the non-homologous end-joining (NHEJ) pathway. Several potentially functional polymorphisms of the XRCC4 gene have been implicated in breast cancer risk, but individually published studies showed inconclusive results. The aim of this meta-analysis was to investigate the association between XRCC4 polymorphisms and the risk of breast cancer. METHODS: The MEDLINE, EMBASE, Web of science and CBM databases were searched for all relevant articles published up to June 20, 2012. Potential associations were assessed with comparisons of the total mutation rate (TMR), complete mutation rate (CMR) and partial mutation rate (PMR) in cases and controls. Statistical analyses were performed using RevMan 5.1.6 and STATA 12.0 software. RESULTS: Five studies were included with a total of 5,165 breast cancer cases and 4,839 healthy controls. Meta-analysis results showed that mutations of rs2075686 (C>T) and rs6869366 (G>T) in the XRCC4 gene were associated with increased risk of breast cancer, while rs2075685 (G>T) and rs10057194 (A>G) might decrease the risk of breast cancer. However, rs1805377 (A>G), rs1056503 (G>T), rs28360317 (ins>del) and rs3734091 (A>G) polymorphisms of XRCC4 gene did not appear to have an influence on breast cancer susceptibility. CONCLUSION: Results from the current meta-analysis suggest that the rs2075685 (G>T) and rs6869366 (G>T) polymorphisms of the XRCC4 gene might increase the risk of breast cancer, whereas rs2075685 (G>T) and rs10057194 (A>G) might be protective factors.

Vascular endothelial growth factor +936C/T polymorphism and gastric cancer risk: A meta-analysis.

The aim of this study was to determine whether the vascular endothelial growth factor (VEGF) +936C/T polymorphism confers susceptibility to gastric cancer (GC) by conducting a meta-analysis. Publications addressing the association between the VEGF +936C/T polymorphism and GC risk were selected from the Pubmed, Embase and CBM databases. Data were extracted from the studies by two independent reviewers. The meta-analysis was performed using RevMan 5.0.25 and STATA 9.2 software. From these data, the odds ratio (OR) with 95% confidence interval (CI) was calculated. Finally, 8 case-control studies were retrieved reporting a total of 2,131 gastrointestinal cancer patients and 2,670 controls. Meta-analysis results showed that there was no significant association between the VEGF +936C/T polymorphism and GC risk in all comparisons of the T allele vs. C allele (OR=1.08, 95% CI 0.90-1.30, P=0.42), CT+TT vs. CC (OR=1.08, 95% CI 0.87-1.34, P=0.49), TT vs. CC+CT (OR=1.14, 95% CI 0.85-1.53, P=0.37), TT vs. CC (OR=1.18, 95% CI 0.87-1.59, P=0.28) and TT vs. CT (OR=1.11, 95% CI 0.79-1.56, P=0.56). This meta-analysis confirms that there is a lack of association between the VEGF +936C/T polymorphism and GC risk.