New Insights into Prostate Cancer Susceptibility in European Caucasians: A Systematic Review and Meta-Analysis of CYP3A4 Pharmacogene

欧洲白种人前列腺癌易感性的新见解:CYP3A4 药理基因的系统评价和荟萃分析

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Abstract

BACKGROUND/OBJECTIVES: Prostate cancer is the most frequent male malignancy. The incidence of disease varies among different ethnic groups. CYP3A polymorphisms are candidates for prostate cancer susceptibility studies. The aim of the present study is to investigate the ethnicity-related clinical impact of CYP3A4 variants on prostate cancer risk. METHODS: A systematic literature search and meta-analysis were conducted according to PRISMA guidelines. A total of 10 eligible studies, including 3116 prostate cancer cases and 3008 healthy controls, were analyzed. We evaluated the association between the CYP3A4*1B (rs2740574, -392 A > G) variant and prostate cancer risk in European Caucasians. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using six genetic models. Data were analyzed using fixed and random-effects models based on the I2 value of heterogeneity magnitude. Funnel plots and Egger's linear regression tests were used to assess publication bias. RESULTS: CYP3A4*1B was associated with prostate cancer susceptibility in the allele (G vs. A: OR = 1.32, CI = 0.91-1.93), dominant (AG + GG vs. AA OR = 1.41, CI = 0.95-2.09), recessive (GG vs. AA + AG, OR = 1.82, CI = 1.26-2.63), homozygous (GG vs. AA, OR = 1.92, CI = 1.32-2.77), heterozygous model (AG vs. AA, OR = 1.31, CI = 0.89-1.93) and co-dominant model (AG vs. AA + GG; OR = 1.27, CI = 0.88-1.85). Significant heterogeneity characterized the allele, as well as the dominant model (I2 = 84.1%, I2 = 80.0%). Egger's tests (p < 0.05) and funnel plots did not identify publication bias. CONCLUSIONS: The present meta-analysis indicates that the G allele and GG genotype might affect prostate cancer susceptibility in European Caucasians; however, the validity and reliability of the results need to be examined in future research.

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