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35 (4), 3709-3715.

Full Text: 2014\Tum Biol35, 3709.pdf

Abstract: The prognostic significance of CXC chemokine receptor type 4 (CXCR4) for survival of patients with esophageal cancer remains controversial. To investigate its expression impact on clinicopathological features and survival outcome, a meta-analysis was performed. A comprehensive search in the PubMed, Embase, and Web of Science (up to October 8, 2013) was performed for relevant studies using multiple search strategies. Correlation between CXCR4 expression and clinicopathological features and overall survival (OS) was analyzed. A total of 1,055 patients with esophageal cancer from seven studies were included. The pooled odds ratios (ORs) which indicated CXCR4 expression was associated with tumor depth (OR = 0.35, confidence interval (CI) = 0.27-0.47, P < 0.00001), status of lymph node (OR = 0.36, CI = 0.21-0.61, P < 0.0002), TNM (tumor, node, metastasis) stage (OR = 0.38, CI = 0.25-0.56, P < 0.00001), and histological type (OR = 1.81, CI = 1.07-3.05, P = 0.03). Poor overall survival of esophageal cancer was found to be significantly related to CXCR4 overexpression (hazard ratio (HR) 1.49, 95 % CI = 1.24-1.80, P < 0.0001), whereas combined ORs exhibited that CXCR4 expression has no correlation with gender or tumor differentiation. Based on the published studies, CXCR4 overexpression in patients with esophageal cancer indicated worse survival outcome and was associated with common clinicopathological poor prognostic factors.

Keywords: Cancer, Confidence, Correlation, Cxcl12, Cxcr4, Differentiation, Disease, Esophageal Cancer, Expression, Gender, Hazard, Immunity, Impact, Interval, Lymph-Node Metastasis, Meta Analysis, Meta-Analysis, Metaanalysis, Metastasis, Microenvironment, Outcome, P, Patients, Patterns, Prognosis, Prognostic, Prognostic Factors, Protein, Pubmed, Science, Search Strategies, Significance, Squamous-Cell Carcinoma, Survival, Tumor, Tumor-Cells, Web Of Science

? Zhu, W.J., Lu, L., Li, Y., Yao, J. and Xu, B.N. (2014), The effects of p53 Arg72Pro polymorphism on glioma susceptibility: A meta-analysis. Tumor Biology, 35 (4), 3725-3730.

Full Text: 2014\Tum Biol35, 3725.pdf

Abstract: The potentially functional polymorphism Arg72Pro in p53 gene has been implicated in glioma risk, but published studies have mixed findings. The aim of current investigation was to identify whether p53 Arg72Pro polymorphism was significantly associated with the risk of glioma. By searching the databases of PubMed, EMBASE, and Web of Science, our meta-analysis included ten eligible studies consisting of 2,645 glioma cases and 3,920 control subjects. The association between p53 Arg72Pro polymorphism and glioma risk was assessed by summarizing the odds ratios (ORs) with the corresponding 95 % confidence intervals (CIs). We found that there was no overall risk of glioma in relation to any genetic model of p53 Arg72Pro polymorphism. Similar results were implicated in the analyses which are subgrouped by ethnicity and source of controls. This nonsignificant association remained stable when analyses were restrained to the studies consistent with HWE. In conclusion, our meta-analysis, based on the combined data from published papers before May 2013, reveals no evidence for significant association between p53 Arg72Pro polymorphism and glioma risk.

Keywords: Analyses, Arg72pro Polymorphism, Association, Brain-Tumors, Codon 72 Polymorphism, Confidence, Confidence Intervals, Control, Data, Databases, DNA-Repair Genes, Effects, Embase, Ethnicity, Evidence, Gene, Genetic, Glioma, Grade, Intervals, Investigation, Meningioma, Meta Analysis, Meta-Analysis, Metaanalysis, Model, P53, Papers, Polymorphism, Pubmed, Risk, Science, Sensitivity, Source, Tp53 Mutations, Variants, Web Of Science

? Zhao, H.Y., Cai, W.S., Su, S.T., Zhi, D.B., Lu, J. and Liu, S. (2014), Allergic conditions reduce the risk of glioma: A meta-analysis based on 128,936 subjects. Tumor Biology, 35 (4), 3875-3880.

Full Text: 2014\Tum Biol35, 3875.pdf

Abstract: Many studies have investigated the association between the allergic conditions and the risk of glioma. However, the evidence is inadequate to draw robust conclusions because most studies were generally small and conducted in heterogeneous populations. To shed light on these inconclusive findings, we conducted a meta-analysis of studies relating the allergic conditions to the risk of glioma. We identified the relevant studies by searching ISI Web of Science, PubMed, EMBASE, Chinese National Knowledge Infrastructure (CNKI) databases, and Wanfang database by October 2013. We included studies that reported odds ratio (OR) or hazard ratio (HR) with its 95 % confidence interval (CI) for the association between the allergic condition and the risk of glioma. Eighteen independent publications, with 9,986 glioma cases and 118,950 controls, were included. Our results showed that allergic condition was reversely associated with the risk of glioma (OR = 0.78, 95 % CI 0.73-0.83, P < 0.001). The results of our meta-analysis indicated that allergic conditions significantly reduce the risk of glioma.

Keywords: Adult Brain-Tumor, Allergy, Association, Chinese, Cohort, Confidence, Database, Databases, Embase, Epidemiology, Evidence, Glioblastoma, Glioma, Hazard, History, Interval, ISI, ISI Web Of Science, Knowledge, Meta Analysis, Meta-Analysis, Metaanalysis, Odds Ratio, P, Plasma Ige, Populations, Publications, Pubmed, Radiation, Risk, Science, Small, Survival Rates, Web Of Science, XRCC3 Thr241met Polymorphism

? Zhang, Y., Li, Z.F., Zhong, Q., Zhou, W.G., Chen, X.J., Chen, X.H., Fang, J.G. and Huang, Z.G. (2014), Polymorphisms of the XPC gene may contribute to the risk of head and neck cancer: A meta-analysis. Tumor Biology, 35 (4), 3917-3931.

Full Text: 2014\Tum Biol35, 3917.pdf

Abstract: Polymorphisms of the XPC gene have been reported to be associated with an increased risk of head and neck cancer (HNC), though the exact biological effect is still unclear. Genetic association studies (GAS) investigating the associations between three common polymorphisms (PAT, Lys939Gln, and Ala499Val) of the XPC gene and HNC risk have produced contradictory and inconclusive results. The aim of this meta-analysis is to evaluate the contributions of these polymorphisms to the risk of HNC. A literature search was conducted in the PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure databases to indentify eligible studies. Pooled odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were used to evaluate the strength of the associations under a fixed- or random-effect model according to heterogeneity test. Twelve case-control studies were included in this meta-analysis with a total of 3,078 HNC patients and 4,311 healthy controls. For XPC PAT, a significant overall association was found under all major genetic models. Stratified analyses further indicated significant associations in the Caucasian, population-based, non-PCR-RFLP, esophageal cancer and oral cancer subgroups. For XPC Lys939Gln, few significant results were found in either the overall analysis or stratified analyses. For XPC Ala499Val, the combined results revealed a significantly increased risk of HNC for carriers of the 499Val allele. This meta-analysis shows that the XPC PAT and Ala499Val polymorphisms may be associated with an increased risk of HNC, while XPC Lys939Gln may not be associated with HNC risk. Despite some limitations, this meta-analysis establishes solid statistical evidence for an association between XPC genetic polymorphisms and HNC risk that warrants further validation.

Keywords: Analyses, Analysis, Association, Biological, Bladder-Cancer, Cancer, Case-Control, Case-Control Studies, Caucasian, China, Confidence, Confidence Intervals, Damage, Databases, DNA-Repair, Esophageal Cancer, Evidence, Excision-Repair Pathway, Gas, Gene, Genetic, Genetic Polymorphisms, Genome Maintenance, Group C Protein, Head And Neck Cancer, Heterogeneity, Intervals, Knowledge, Literature, Literature Search, Meta Analysis, Meta-Analysis, Metaanalysis, Model, Models, Neck, Oral, Patients, Polymorphisms, Population, Population Based, Population-Based, Pubmed, Risk, Science, Squamous-Cell Carcinoma, Strength, Susceptibility, Validation, Web Of Science, XPC

? Li, S., Huang, X.M., Zhong, H.Z., Peng, Q.L., Chen, S.Y., Xie, Y.T., Qin, X. and Qin, A.P. (2014), Low circulating adiponectin levels in women with polycystic ovary syndrome: An updated meta-analysis. Tumor Biology, 35 (5), 3961-3973.

Full Text: 2014\Tum Biol35, 3961.pdf

Abstract: Adiponectin, as an important adipocytokine, plays a pivotal role in the regulation of insulin sensitivity and metabolism. It has been reported that circulating adiponectin levels were decreased in women with polycystic ovary syndrome (PCOS). However, the results remained inconsistent. In order to derive a more precise estimation of this relationship, a large meta-analysis was performed in this study. A comprehensive systematic electronic search was conducted in electronic databases PubMed, EMBASE, and Web of Science up to November 30, 2013. Pooled weighted mean differences (WMDs) with 95 % confidence intervals (CIs) were calculated to estimate the strength of the association. A meta-analysis technique was used to study 38 trials involving 1,944 PCOS women and 1,654 healthy controls. Overall pooled adiponectin levels in women with PCOS were significantly reduced compared with healthy controls (WMD -2.67, 95 % CI -3.22 to -2.13; P = 0.000), yet with significant heterogeneity across studies (I-2 = 95.9 %, P = 0.000). In subgroup analysis by HOMA-IR ratio and total testosterone ratio, inconsistent results were presented. No single study was found to affect the overall results by sensitivity testing. Meta-regression suggested that BMI might contribute little to the heterogeneity between including studies. Cumulative meta-analysis demonstrated the reliability and stability of the meta-analysis results. No evidence of publication bias was observed. Our meta-analysis suggested that circulating adiponectin levels in women with PCOS were significantly lower than those in healthy controls, which indicated that circulating adiponectin might play a role in the development of PCOS.

Keywords: Adiponectin, Adipose-Tissue, Analysis, Association, Bias, Bmi, Body-Mass Index, Confidence, Confidence Intervals, Cumulative Meta-Analysis, Databases, Development, Embase, Evidence, Glucose-Tolerance Test, Heterogeneity, Insulin, Insulin Resistance, Insulin Sensitivity, Insulin-Resistance, Intervals, Leptin-To-Adiponectin, Meta Analysis, Meta-Analysis, Meta-Regression, Metaanalysis, Metabolic Syndrome, Metabolism, Nonobese Women, Obesity, Ovary, Overweight Women, P, Pioglitazone Treatment, Polycystic Ovary Syndrome, Publication, Publication Bias, PubMed, Regulation, Reliability, Role, Science, Sensitivity, Serum-Levels, Stability, Strength, Syndrome, Systematic, Testing, Testosterone, Web of Science, Women

? Shen, Y.H., Chen, S., Peng, Y.F., Shi, Y.H., Huang, X.W., Yang, G.H., Ding, Z.B., Yi, Y., Zhou, J., Qiu, S.J., Fan, J. and Ren, N. (2014), Quantitative assessment of the effect of glutathione S-transferase genes GSTM1 and GSTT1 on hepatocellular carcinoma risk. Tumor Biology, 35 (5), 4007-4015.

Full Text: 2014\Tum Biol35, 4007.pdf

Abstract: Hepatocellular carcinoma (HCC) is one of the most serious health problems worldwide. As in many other diseases, environment and genetic factors are believed to be involved in the pathogenesis of HCC. Numerous epidemiologic investigations including case-control and cohort studies have suggested the association of glutathione S-transferase (GST) genetic polymorphisms and HCC risk. However, some studies have produced conflicting results. Therefore, we performed an updated meta-analysis to clarify this inconsistency and to establish a comprehensive picture of the association of the polymorphisms of GSTM1 and GSTT1 with HCC susceptibility. We searched PubMed, Embase, ISI Web of Science, and CNKI databases to identify eligible studies meeting the inclusion criteria up to August 30, 2013. Odds ratios (ORs) and 95 % confidence intervals (CIs) were used to assess the strength of association. Finally, there were a total of 33 studies with 4,232 cases and 6,601 controls included in this meta-analysis. In the pooled analysis, significantly increased HCC risks were found for null genotype of GSTM1 (OR = 1.31, 95 % CI = 1.07-1.61, P = 0.010, P (heterogeneity) < 10(-5)) and GSTT1 (OR = 1.47, 95 % CI = 1.25-1.74, P < 10(-5), P (heterogeneity) < 10(-5)). Potential sources of heterogeneity were explored by subgroup analysis based on ethnicity, sample size, and source of control. Significant results were found among East Asians and Indians when stratified by ethnicity, while no evidence of significant associations was observed among Caucasian and African populations. In the gene-gene interaction analysis, a statistically significant increased risk for HCC was detected for individuals with combined deletion mutations in both genes compared to those with wild genotypes (OR = 1.88, 95 % CI = 1.41-2.50, P < 10(-4), P (heterogeneity) = 0.004). The present meta-analysis demonstrated that the GSTM1 and GSTT1 null genotype may be associated with an increased risk of HCC and that individuals having the combination of both defective GST genotypes may be more susceptible to developing HCC.

Keywords: Aflatoxin, Analysis, Assessment, Association, Carcinoma, Case-Control, Caucasian, Cohort, Confidence, Confidence Intervals, Control, Criteria, Databases, Deletion, Developing, Diseases, Dna-Repair, Environment, Ethnicity, Evidence, Genes, Genetic, Genetic Polymorphisms, Glutathione, Glutathione S-Transferase (GST), Gstm1, Gstt1, HCC, Health, Hepatitis-B Carriers, Hepatocellular Carcinoma, Heterogeneity, Interaction, Intervals, Investigations, ISI, ISI Web of Science, M1, Meta Analysis, Meta-Analysis, Metaanalysis, Metabolizing Enzymes, Microsomal Epoxide Hydrolase, Mutations, P, Pathogenesis, Polymorphism And Hepatocellular Carcinoma (HCC), Polymorphisms, Population, Populations, PubMed, Quantitative Assessment, Risk, Risks, Sample Size, Science, Size, Source, Sources, Strength, Susceptibility, T1, Web of Science

? Li, H., Fu, W.Y., Gao, X., Xu, Q.F., Wu, H. and Tan, W.L. (2014), Risk of severe diarrhea with dual anti-HER2 therapies: A meta-analysis. Tumor Biology, 35 (5), 4077-4085.

Full Text: 2014\Tum Biol35, 4077.pdf

Abstract: Although promising progress has been made with dual HER2 blockade in patients with HER2-positive breast cancer, whether the strategy of combined HER2 blockade increases the risk of severe diarrhea remains inclusive. In the present study, we investigated the overall incidence and risk of severe diarrhea when patients were treated with a combination of anti-HER2 therapies compared to anti-HER2 monotherapy. Studies that evaluated the administration of an anti-HER2 monotherapy (lapatinib or trastuzumab or pertuzumab) versus anti-HER2 combination therapy (pertuzumab plus trastuzumab or trastuzumab plus lapatinib) in breast cancer were identified from the PubMed database (1966-2013), The Cochrane library, abstracts presented at the American Society of Clinical Oncology annual conference (2004-2013), and the Web of Science database (1998-2013). Eligible studies were those in which the only systematic difference between the study arms was the type of anti-HER2 therapy used. Incidence, relative risk (RR), and 95 % confidence intervals (CIs) were calculated using random effects or fixed-effects models based on the heterogeneity of the included studies. Seven trials were considered eligible. The overall incidence results for severe diarrhea in the combined anti-HER2 therapy and the anti-HER2 monotherapy were 3.48 % (95 % CI: 11.60-15.37 %) and 8.68 % (95 % CI: 7.33-10.03 %), respectively. The odds ratio (OR) of severe diarrhea between anti-HER2 combination therapy and monotherapy was 1.67 (95 % CI: 1.38 -5.57, p = 0.00001). This meta-analysis provides evidence that the incidence rates of severe diarrhea are comparable between anti-HER2 combination therapy and anti-HER2 monotherapy.

Keywords: Adjuvant Chemotherapy, Administration, Breast Cancer, Cancer, Cells, Combination Therapy, Confidence, Confidence Intervals, Database, Diarrhea, Dual Her2 Blockade, Effects, Efficacy, Evidence, Her2, Her2-Positive Breast-Cancer, Heterogeneity, Incidence, Intervals, Lapatinib, Mechanism, Meta Analysis, Meta-Analysis, Metaanalysis, Models, Multicenter, Odds Ratio, Oncology, Open-Label, Patients, Pertuzumab, Plus Trastuzumab, Progress, PubMed, Rates, Relative Risk, Risk, Science, Strategy, Systematic, Therapy, Web of Science

? Li, B., Zhang, J., Wang, L., Li, Y., Jin, J.P., Ai, L.M., Li, C., Li, Z. and Mao, S.D. (2014), MTHFR genetic polymorphisms may contribute to the risk of chronic myelogenous leukemia in adults: A meta-analysis of 12 genetic association studies. Tumor Biology, 35 (5), 4233-4245.

Full Text: 2014\Tum Biol35, 4233.pdf

Abstract: Chronic myelogenous leukemia (CML) is a complex disease with a genetic basis. The genetic association studies (GASs) that have investigated the association between adult CML and 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms have produced contradictory and inconclusive results. The aim of this meta-analysis is to provide a relatively comprehensive assessment of the association of these polymorphisms with adult CML risk. A literature search for eligible GAS published before September 15, 2013 was conducted in PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases. Pooled odds ratios (ORs) with their corresponding 95 % confidence intervals (95 % CIs) were used to evaluate the strength of the association under a fixed or random effect model according to heterogeneity test results. All analyses were performed using the Stata software, version 12.0. Twelve case-control studies were included in this meta-analysis with a total of 932 CML patients and 3,465 healthy controls. For MTHFR C677T (dbSNP: rs1801133, C > T), though the pooled ORs were not significant in the overall population, all the ORs greater than 1 suggested an increased risk of CML for carriers of the risk allele. However, stratified analysis based on genotyping method revealed a significant association in the PCR-restriction fragment length polymorphism (RFLP) subgroup, possibly as a result of heterogeneity. For MTHFR A1298C (dbSNP: rs1801131, A > C), The combined results showed that carriers of the C allele may be associated with a decreased risk of adult CML. Stratified analysis showed that the magnitude of this effect was especially significant among Asians, indicating ethnicity differences in adult CML susceptibility. This meta-analysis shows that the C allele of MTHFR A1298C may be associated with a decreased risk in adult CML, especially among Asians, while MTHFR C677T may not be associated with adult CML risk. However, the development of adult CML may be the result of gene-gene and gene-environment interactions, which should be considered in future individual GAS and subsequent meta-analyses.

Keywords: 5,10-Methylenetetrahydrofolate Reductase, A1298c Polymorphisms, Acute Lymphoblastic-Leukemia, Adult, Analyses, Analysis, Assessment, Association, Case-Control, Case-Control Studies, Cervical-Cancer Risk, China, Chronic, Chronic Myelogenous Leukemia, Chronic Myeloid-Leukemia, Chronicmyelogenous Leukemia, Cml, Colorectal-Cancer, Confidence, Confidence Intervals, Databases, Development, Disease, Dna Methylation, Ethnicity, Folate-Deficiency, Gas, Genetic, Genetic Polymorphisms, Genotyping, Heterogeneity, Intervals, Knowledge, Length, Leukemia, Literature, Literature Search, Magnitude, Meta Analysis, Meta-Analysis, Metaanalysis, Methylenetetrahydrofolate Reductase C677t, Model, Molecular-Biology, Mthfr, Mthfr C677t, Patients, Polymorphism, Polymorphisms, Population, PubMed, Rflp, Risk, Science, Software, Stata, Strength, Version, Web of Science

? Yuan, G.Q., Gao, D.D., Ding, S.F. and Tan, J. (2014), DNA repair gene ERCC1 polymorphisms may contribute to the risk of glioma. Tumor Biology, 35 (5), 4267-4275.

Full Text: 2014\Tum Biol35, 4267.pdf

Abstract: Polymorphisms in excision repair cross-complementing rodent repair deficiency complementation group 1 (ERCC1) gene have been shown to affect individual susceptibility to glioma, though studies have yielded conflicting results. This meta-analysis aims to derive a more precise estimation of the association between ERCC1 C8092A and C118T polymorphisms and glioma risk. A literature search of PubMed, Embase, Web of Science, Cochrane Library, and CBM databases was conducted to identify all eligible studies published before August 5, 2013. Crude odds ratios (ORs) with their corresponding confidence intervals (95 % CIs) were used to assess the strength of this association. A meta-analysis was performed by reviewing seven studies on the C8092A polymorphism (2,978 cases and 4,051 controls) and four studies on the C118T polymorphism (1,390 Asian cases and 1,546 Asian controls). Pooled analysis yielded a significant association between the C8092A variant genotype and increased risk of glioma. As for ethnicity, the A allele was associated with increased risk of glioma in Asians, while no similar finding was observed in Caucasians. Stratified analyses by histological subtype indicated that the C8092A polymorphism showed a significant association with the risk of non-glioblastoma multiforme. For the C118T polymorphism, increased glioma susceptibility was also observed among Asians. Taken together, results from our meta-analysis support the view that common variants in ERCC1 may contribute to susceptibility to glioma, especially in Asians. However, further studies investigating the significance of these two polymorphisms as markers of susceptibility to and disease progression of glioma are still needed.

Keywords: Adult Glioma, Analyses, Analysis, Asian, Association, Cancer, Chinese Population, Classification, Confidence, Confidence Intervals, Databases, Disease, Dna, Ercc1, Ethnicity, Gene, Glioma, Intervals, Literature, Literature Search, Meta Analysis, Meta-Analysis, Metaanalysis, Nervous-System, Polymorphism, Polymorphisms, Primary Brain-Tumors, Progression, PubMed, Risk, Science, Significance, Strength, Support, Susceptibility, Web of Science, Xrcc3 Thr241met Polymorphism

? Wang, H., Ren, L., He, Y.F., Wei, Y., Chen, Z.G., Yang, W.G., Fu, Y.P., Xu, X.Y., Fu, W.G., Hu, G.F. and Lou, W.H. (2014), Association between cytochrome P450 2C9 gene polymorphisms and colorectal cancer susceptibility: Evidence from 16 case-control studies. Tumor Biology, 35 (5), 4317-4322.

Full Text: 2014\Tum Biol35, 4317.pdf

Abstract: Previous epidemiological studies have evaluated the association between common variations of cytochrome P450 (CYP)2C9 (430C > T and 1075A > C) and the risk of colorectal cancer (CRC) with conflicting results. To derive a more precise estimation of the relationship between these CYP2C9 polymorphisms and CRC, a meta-analysis was performed. PubMed, Embase, CNKI, and Web of Science databases were searched. A total of 16 studies including 9,463 cases and 11,416 controls were identified. Potential sources of heterogeneity including ethnicity, sample size of study, genotyping method, diagnostic criteria, and outcome were systematically assessed. Overall, the summary odds ratio of 430T variant for CRC was 0.92 (95 % confidence interval (CI) 0.86-0.98; P = 0.012) and 1.39 (95 % CI 1.07-1.81; P = 0.013) for colorectal adenomas (CRAs). As for CYP2C9 1075A > C polymorphism, no significant results were observed in overall and subgroup analysis. There was no evidence of publication bias. In conclusion, there is evidence to indicate a significant association between CYP2C9 430C > T polymorphism and CRC/CRA risk.

Keywords: Adenoma, Analysis, Association, Bias, Cancer, Cancer Susceptibility, Carcinoma, Case-Control, Case-Control Studies, Cigarette-Smoking, Colorectal Adenomas, Colorectal Cancer, Confidence, Criteria, Cyp2c9, Cytochrome, Cytochrome P450, Databases, Diagnostic, Diagnostic Criteria, Ethnicity, Evidence, Gene, Genotyping, Heterogeneity, Interval, Meta Analysis, Meta-Analysis, Metaanalysis, Odds Ratio, Outcome, P, Polymorphism, Polymorphisms, Publication, Publication Bias, PubMed, Risk, Sample Size, Science, Sites, Size, Sources, Ugt1a6, Variants, Web of Science, Web of Science Databases, Xenobiotic-Metabolizing Enzymes

? Ping, W., Sun, W., Zu, Y.K., Chen, W.S. and Fu, X.N. (2014), Clinicopathological and prognostic significance of hypoxia-inducible factor-1 in esophageal squamous cell carcinoma: A meta-analysis. Tumor Biology,



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