Controls could be composed of healthy subjects, chronic liver disease (CLD), including chronic hepatitis (CH) and LC. CLD was either histologically proven or diagnosed based on concordant clinical, biological, and morphological criteria. Review articles and articles that did not provide genotype data were excluded. Data extraction and synthesis learn more The following information was extracted from each study: first
author’s surname, year of publication, ethnicity of study population, country where study was conducted, and the number of cases and controls for each C282Y and H63D genotype. When specific results were not reported, we used available tabular data to calculate them. Statistical methods To compare the odds ratio (OR) on the same baseline, we used crude OR to conduct the meta-analysis. The effect of association was indicated as crude OR with the corresponding 95% confidence intervals (CIs). Because of relatively small sample sizes of individual studies and low frequency of variant alleles and the practical clinical value, we performed meta-analysis only in two models: dominant PARP inhibitor model (YY+CY vs. CC or DD+HD vs. HH) and
allele contrast (Y vs. C or D vs. H). The pooled OR was estimated using the FE model (DerSimonian & Laird) [22]. The heterogeneity between Phospholipase D1 studies was tested using the Q statistic [23]. If P < 0.10, the heterogeneity was considered
statistically significant, and the RE model was then used. Heterogeneity was also quantified using the I2 metric, which is independent of the number of studies in the meta-analysis (I2 < 25% = no heterogeneity; I2 = 25-50% = moderate heterogeneity; I2 > 50% = large or extreme heterogeneity) [24]. The potential small-study bias was tested using the Egger regression test asymmetry [25] and the Begg’s test for funnel plot, which is based on Kendall’s tau [26]. Sensitivity analysis was performed by omitting one study at a time to assess the influence of individual studies on meta-analysis. The distribution of the genotypes in the control group was tested for Hardy-Weinberg equilibrium using a goodness-of-fit Chi-square test. All analyses above were conducted using the STATA version 10.0 software (Stata Corp, College GSK1904529A concentration Station, Texas). All P-values were two-sided. A p value less than 0.05 was considered statistically significant. The statistical power was calculated using the PS software [27]. In order to assess the reliability of the positive association, we calculated false positive report probability (FPRP) [28]. An Excel spreadsheet to calculate FPRP is included with the online material http://jncicancerspectrum.oupjournals.org/jnci/content/vol96/issue6. If FPRP < 0.