Evidence has changed over time. In this article, we conducted cumulative

Evidence has changed over time. In this article, we conducted get SP600125 cumulative meta-analyses of the 2 associations by categorizing the studies by publication time. S2 Fig displays the results from the cumulative meta-analysis of the association between the EPHX1 Tyr113His polymorphism (His/His+ Tyr/His vs. Tyr/Tyr) and overall HNC in chronological order. The results showed a minimally significant association between the EPHX1 Tyr113His polymorphism and HNC risk when the data were categorized by publication year. A lack of significant associations between the EPHX1 QVD-OPH site His139Arg polymorphism and HNC risk was observed when the data were categorized by publication year (S2 Fig).Publication biasPublication bias appears if no significant findings remain unpublished, which will artificially expand the apparent magnitude of an effect. In this meta-analysis, funnel plot, Begg’s and Egger’s tests were used to evaluate publication bias of the literature on HNC. S3 Fig and S4 Fig show funnel plots of overall HNC risk and EPHX1 polymorphisms with basic symmetry, which suggested a lack of publication bias. Moreover, the results of statistical analysis revealed that publication bias was not evident, with the exception of the meta-analysis of the EPHX1 His139Arg homozygote comparison [(1) EPHX1Tyr113His, His/His vs. Tyr/Tyr: Begg’s test P = 0.12, Egger’s test P = 0.34; Tyr/His vs. Tyr/Tyr: Begg’s test P = 0.40, Egger’s test P = 0.25; dominant model: Begg’s test P = 0.18, Egger’s test P = 1.30; recessive model: Begg’s test P = 0.12, Egger’s test P = 0.46. (2) EPHX1 His139Arg, Arg/Arg vs. His/His: Begg’s test P = 0.28, Egger’s test P = 0.05; Arg/His vs. His/His: Begg’s test P = 0.86, Egger’s test P = 0.16; dominant model: Begg’s test P = 0.86, Egger’s test P = 0.61; recessive model: Begg’s test P = 0.86, Egger’s test P = 0.59](Table 4).PLOS ONE | DOI:10.1371/journal.pone.0123347 April 29,10 /EPHX1 Polymorphisms on the Risk of HNC: A Meta-AnalysisTable 4. Pooled data for EPHX1and HNC risk in meta-analyses. EPHX1 Tyr113His His/His vs. Tyr/Tyr P-Publication bias Heterogeneity test Egger Begg P value I2 0.34 0.12 0.00 66.4 Tyr/His vs. Tyr/Tyr 0.25 0.40 0.02 55.1 His/His+ Tyr/ His vs. Tyr/ Tyr 1.30 0.18 0.01 63.8 His/His vs. Tyr/His +Tyr/ Tyr 0.46 0.12 0.01 58.2 Arg/Arg vs. His/ His 0.05 0.28 0.51 0 EPHX1 His139Arg Arg/His vs. His/His 0.16 0.86 0.00 80.9 Arg/Arg+Arg/ His vs. His/His 0.61 0.86 0.02 53.0 Arg/Arg vs. Arg/His+His/ His 0.59 0.86 0.61 01. Fixed effects models were used, weighted by the inverse variance; 2. P < 0.1 is considered statistically significant for Q statistics; I2 is interpreted as the proportion of total variation contributed by between-study variation; 3. Egger's test and Begg's test to evaluate publication bias, P < 0.05 is considered doi:10.1371/journal.pone.0123347.tDiscussionSome previous articles reported a significant association between EPHX1polymorphism and several human diseases, such as type 2 diabetes mellitus [36], alcohol dependence [37], and chronic obstructive pulmonary disease [38], while others found no such association [39?1]. In this meta-analysis, the pooled results indicated that subjects carrying the EPHX1 Tyr113His genotype had an increased risk of developing HNC. Our approach also allowed us to identify some potential differences, such as ethnicity, source of controls, study sample size and others. In different ethnicities, the EPHX1 polymorphism did not have a significant association with HNC risk. Our result diff.Evidence has changed over time. In this article, we conducted cumulative meta-analyses of the 2 associations by categorizing the studies by publication time. S2 Fig displays the results from the cumulative meta-analysis of the association between the EPHX1 Tyr113His polymorphism (His/His+ Tyr/His vs. Tyr/Tyr) and overall HNC in chronological order. The results showed a minimally significant association between the EPHX1 Tyr113His polymorphism and HNC risk when the data were categorized by publication year. A lack of significant associations between the EPHX1 His139Arg polymorphism and HNC risk was observed when the data were categorized by publication year (S2 Fig).Publication biasPublication bias appears if no significant findings remain unpublished, which will artificially expand the apparent magnitude of an effect. In this meta-analysis, funnel plot, Begg's and Egger's tests were used to evaluate publication bias of the literature on HNC. S3 Fig and S4 Fig show funnel plots of overall HNC risk and EPHX1 polymorphisms with basic symmetry, which suggested a lack of publication bias. Moreover, the results of statistical analysis revealed that publication bias was not evident, with the exception of the meta-analysis of the EPHX1 His139Arg homozygote comparison [(1) EPHX1Tyr113His, His/His vs. Tyr/Tyr: Begg's test P = 0.12, Egger's test P = 0.34; Tyr/His vs. Tyr/Tyr: Begg's test P = 0.40, Egger's test P = 0.25; dominant model: Begg's test P = 0.18, Egger's test P = 1.30; recessive model: Begg's test P = 0.12, Egger's test P = 0.46. (2) EPHX1 His139Arg, Arg/Arg vs. His/His: Begg's test P = 0.28, Egger's test P = 0.05; Arg/His vs. His/His: Begg's test P = 0.86, Egger's test P = 0.16; dominant model: Begg's test P = 0.86, Egger's test P = 0.61; recessive model: Begg's test P = 0.86, Egger's test P = 0.59](Table 4).PLOS ONE | DOI:10.1371/journal.pone.0123347 April 29,10 /EPHX1 Polymorphisms on the Risk of HNC: A Meta-AnalysisTable 4. Pooled data for EPHX1and HNC risk in meta-analyses. EPHX1 Tyr113His His/His vs. Tyr/Tyr P-Publication bias Heterogeneity test Egger Begg P value I2 0.34 0.12 0.00 66.4 Tyr/His vs. Tyr/Tyr 0.25 0.40 0.02 55.1 His/His+ Tyr/ His vs. Tyr/ Tyr 1.30 0.18 0.01 63.8 His/His vs. Tyr/His +Tyr/ Tyr 0.46 0.12 0.01 58.2 Arg/Arg vs. His/ His 0.05 0.28 0.51 0 EPHX1 His139Arg Arg/His vs. His/His 0.16 0.86 0.00 80.9 Arg/Arg+Arg/ His vs. His/His 0.61 0.86 0.02 53.0 Arg/Arg vs. Arg/His+His/ His 0.59 0.86 0.61 01. Fixed effects models were used, weighted by the inverse variance; 2. P < 0.1 is considered statistically significant for Q statistics; I2 is interpreted as the proportion of total variation contributed by between-study variation; 3. Egger's test and Begg's test to evaluate publication bias, P < 0.05 is considered doi:10.1371/journal.pone.0123347.tDiscussionSome previous articles reported a significant association between EPHX1polymorphism and several human diseases, such as type 2 diabetes mellitus [36], alcohol dependence [37], and chronic obstructive pulmonary disease [38], while others found no such association [39?1]. In this meta-analysis, the pooled results indicated that subjects carrying the EPHX1 Tyr113His genotype had an increased risk of developing HNC. Our approach also allowed us to identify some potential differences, such as ethnicity, source of controls, study sample size and others. In different ethnicities, the EPHX1 polymorphism did not have a significant association with HNC risk. Our result diff.