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

## TL;DR

This study finds that a specific genetic variant in European Caucasians may increase prostate cancer risk.

## Contribution

A meta-analysis linking CYP3A4*1B polymorphism to prostate cancer risk in European Caucasians.

## Key findings

- The G allele of CYP3A4*1B is associated with increased prostate cancer risk in European Caucasians.
- The GG genotype shows a significant association with prostate cancer susceptibility in homozygous and recessive models.
- Egger’s tests confirm no publication bias in the meta-analysis findings.

## Abstract

Prostate cancer is the most frequently diagnosed malignancy in men worldwide. The study aimed to assess the impact of CYP3A4*1B polymorphism on prostate cancer risk in populations of European Caucasian ancestry. Despite the heterogeneity observed in the allele and in the dominant model, I2 = 84.1% and I2 = 80.0%, respectively, the present meta-analysis of 10 studies, encompassing 3116 patients and 3008 healthy controls sourced from PubMed and Cochrane Library, reveals a significant association for the homozygous model (GG vs. AA, OR = 1.92, CI = 1.32–2.77) and the recessive (GG vs. AA + AG, OR = 1.82, CI = 1.26–2.63). Egger’s tests (p < 0.05) did not indicate a publication bias. These findings suggest a higher prostate cancer risk, especially for men who are carriers of the G allele. Further experimental data from genetic association studies are necessary to clarify the relationship between CYP3A4*1B (rs2740574, −392 A > G) polymorphism and prostate cancer susceptibility in European Caucasians.

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.