Association of angiotensin-converting enzyme insertion/deletion (ACE I/D) gene polymorphism with susceptibility to prostate cancer: an updated meta-analysis

Abstract

Objective This meta-analysis aims to explore the association between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and susceptibility to prostate cancer (PCa). Methods We searched studies related to ACE I/D polymorphism and susceptibility to PCa through PubMed, Web of Science, Embase, Cochrane Library, and Scopus databases from inception to June 1, 2022. Five gene models, including allelic, dominant, recessive, homozygote, and heterozygote models, were analyzed. The pooled odds ratio (OR) was calculated using Stata 15.0 software. Publication bias was judged by the funnel plot and Egger’s test, with the robustness of the findings verified by sensitivity analysis. Results Eight published articles (including ten studies) were identified. The pooled results showed that ACE I/D locus polymorphism was significantly correlated with the risk of PCa under all gene models except for the heterozygous model (D vs. I: OR= 1.58, 95% CI: 1.14–2.21; DD vs. DI+II: OR=1.68, 95% CI: 1.11–2.54; DD+DI vs. II: OR=1.76, 95% CI: 1.11–2.80; DI vs. II: OR= 1.44, 95% CI: 0.99–2.10; DD vs. II: OR= 2.12, 95% CI: 1.15–3.93). Subgroup analysis based on genotype frequencies in the control group meeting Hardy-Weinberg equilibrium showed statistically significant differences in all gene models. The funnel plot and Egger’s test indicated no publication bias. The sensitivity analysis verified the robustness of the conclusions obtained in this meta-analysis. Conclusion ACE I/D locus polymorphism correlates to PCa risk. Allele D, genotype DD+DI, and DD at the ACE I/D locus increase susceptibility to PCa and can therefore serve as a potential diagnostic and screening molecular marker for PCa patients.

Genetic Modulation of HPV Infection and Cervical Lesions: Role of Oxidative Stress-Related Genes

“…Previously, an enhanced ACE activity was verified in tumor progression in cervical carcinoma [48,49]. Regarding other types of cancer, the following has been described in gastric and colorectal cancer: a higher ACE1 expression in the tumor microenvironment compared to healthy tissues [50], a higher susceptibility to prostate cancer in carriers of the D allele [51], and a lower incidence of breast cancer for the genotypes with lower gene expression and for women receiving treatment with iACEs [52]. Although we could not find an association of this gene with cervical lesions, we know that HPV infection is necessary for carcinoma development.…”

More evidence for widespread antagonistic pleiotropy in polymorphic disease alleles

“…In humans, the ACE locus has a highly-studied polymorphism defined by the insertion I ) or deletion D ) of 287 base pairs in intron 16, with the presence of the D allele raising the levels of ACE protein in plasma ( Rigat et al, 1990 ). Increased levels of ACE protein and the D allele have been associated with an increased risk of hypertension ( Higaki et al, 2000 ; Montes-de-Oca-García et al, 2021 ), coronary artery disease ( Nakai et al, 1994 ), myocardial infarction ( Chen et al, 2013 ), polycystic ovary syndrome ( Ożegowska et al, 2016 ), and prostate cancer ( Du et al, 2022 ).…”

Contribution of Endothelial Dysfunction to Cancer Susceptibility and Progression: A Comprehensive Narrative Review on the Genetic Risk Component

“…The ACE Indel is also referred to as contributing to the PCa risk in Latino and Asian ethnic groups [77,78]. Moreover, DD carriers also present more advanced stages of the disease and early-age diagnostics [79][80][81][82][83]. The same genotype seems to be related to an increased risk of oral precancerous lesions in betel quid chewers and OSCC and lymph node metastasis in men [84,85].…”