Interleukin-18 (IL-18) plays a potential pathological role in recurrent pregnancy loss (RPL). The results of published studies on the relationship between IL-18 gene promoter polymorphisms (-137G/C and-607C/A) and RPL risk remain controversial. This meta-analysis was performed to evaluate the association of IL-18, -137G/C and-607C/A gene polymorphisms with the risk of RPL under recessive, dominant and additive genetic models. A literature search was conducted in Medline, Embase and Web of Science for studies that described the effect of IL-18 gene polymorphisms on RPL risk. The numbers of each -137G/C and-607C/A genotype in the case and control groups were extracted. Quality of the original studies' methodology was also assessed. Meta-analysis was performed using Stata 13.1 software and the fixed effect model was used. Five articles were included in this meta-analysis. No significant heterogeneity between the studies was noted. The IL-18 -137 G/C polymorphism was significantly associated with an increased risk of RPL under a recessive genetic model (CC vs. GG + CG: odds ratio = 1.56, 95% confidence interval = 1.13 ~ 2.15). For the -607C/A mutation, we failed to find any association under any genetic models. The Egger's regression asymmetry test showed no publication bias. Our present study indicates a positive association between the CC genotype of the IL-18 -137G/C gene and RPL risk. Future well-designed large studies are needed to validate the association between IL-18 gene polymorphisms and the risk of RPL.

The dose-response relationship between folate and the risk of esophageal cancer (EC) is not clear. To further elucidate their relationships, we carried out a dose-response meta-analysis of folate intake, serum folate, and the risk of EC. PubMed, Embase, Web of Science, and China National Knowledge Infrastructure were searched for observational studies until September 2016. Then, we carried out a systematic review and dose-response meta-analysis using Stata 14.0 software. Subgroup analyses were further carried out according to study characteristics and adjustment confounders. A total of 23 studies with a total of 3886 patients were enrolled in this study. The pooled odds ratios for EC in the highest versus the lowest levels of folate intake and serum folate were 0.64 (0.54-0.76, P<0.001) and 0.45 (0.19-1.07, P=0.071), respectively. Dose-response meta-analyses were carried out to assess associations between folate intake, serum folate, and EC risk. When serum folate is 10 μg/l higher than the lowest reference dosage (3.44 μg/l), EC decreased risk with an increase in serum folate levels. When folate intake is 50 μg/day higher than the lowest reference dosage (125.21 μg/day), the EC risk is decreased with an increase in folate intake. Finally, the results support that folate can promote public health through decreasing EC risk in a certain dosage range; otherwise, the protective effects might be reduced.

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