# Association Aamong Ppolymorphisms in the Aapoptosis‐Rrelated NKX3‐1, Caspase‐3, Caspase‐9, and BCL‐2 Genes and Prostate Cancer Susceptibility From 9706 Cases and 12,567 Controls

**Authors:** Yanyan Feng, Zhenting Feng, Dan Li, Jiandong Gui, Zhihong Song, Xiaohua Xie, Lijie Zhu, Yuanyuan Mi

PMC · DOI: 10.1002/cnr2.70206 · 2025-05-08

## TL;DR

This study finds that certain genetic variations in genes related to cell death are linked to increased or decreased risk of prostate cancer.

## Contribution

The study provides new evidence linking specific polymorphisms in apoptosis-related genes to prostate cancer risk.

## Key findings

- NKX3-1 rs2228013, CASP9 rs1052571, and CASP9 rs4645982 polymorphisms are associated with increased prostate cancer risk.
- CASP3 rs4647603 polymorphism is associated with reduced prostate cancer risk.
- The study analyzed data from 9706 cases and 12,567 controls to identify these associations.

## Abstract

While there is a growing volume of evidence suggesting that relatively prevalent functional polymorphisms present within apoptosis‐related genes may influence human prostate cancer (PCa) susceptibility, the clinical relevance of these findings remains inconclusive.

This meta‐analysis was thus developed with the goal of generating more precise estimates of the relationships between polymorphisms in four apoptosis‐associated genes (NKX3‐1, caspase‐3, caspase‐9, and BCL‐2) and the risk of PCa.

The PubMed, Web of Science, Google Scholar, Embase, Cochrane Library, and SinoMed (CNKI and Wanfang) databases were searched for relevant studies published through December 20, 2023, using the following keywords: “polymorphism” or “variant” and “carcinoma” or “cancer” or “tumor” and “NKX3‐1,” “CASP3” or “Caspase‐3,” “CASP9” or “Caspase‐9,” “BCL‐2” or “B‐cell lymphoma” and “prostate cancer” or “PCa” or “prostate adenocarcinoma.” This approach led to the identification of 22 case–control studies related to the association between apoptosis‐related gene polymorphisms and PCa susceptibility enrolling 9706 cases and 12 567 controls. Subsequent analyses revealed that the NKX3‐1 rs2228013, CASP9 rs1052571, and CASP9 rs4645982 polymorphisms were associated with greater PCa risk, whereas the CASP3 rs4647603 polymorphism was associated with a risk reduction.

These findings provide strong evidence for the potential contributions of polymorphisms in the apoptosis‐related caspase‐3, caspase‐9, and NKX3‐1 genes in the onset and progression of PCa.

## Linked entities

- **Genes:** NKX3-1 (NK3 homeobox 1) [NCBI Gene 4824], CASP3 (caspase 3) [NCBI Gene 836], CASP9 (caspase 9) [NCBI Gene 842], BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596]
- **Diseases:** prostate cancer (MONDO:0005159), PCa (MONDO:0012155)

## Full-text entities

- **Genes:** CASP9 (caspase 9) [NCBI Gene 842] {aka APAF-3, APAF3, ICE-LAP6, MCH6, PPP1R56}, NKX3-1 (NK3 homeobox 1) [NCBI Gene 4824] {aka BAPX2, NKX3, NKX3.1, NKX3A}, CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}
- **Diseases:** B-cell lymphoma (MESH:D016393), PCa (MESH:D011471), prostate adenocarcinoma (MESH:D000230), cancer (MESH:D009369)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** rs4645982, rs4647603, rs2228013, rs1052571

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12062516/full.md

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Source: https://tomesphere.com/paper/PMC12062516