Exploring the Association Between PRC2 Genes Variants and Lung Cancer Risk in Chinese Han Population

Abstract

Background

Genetic susceptibilities play a large role in the pathogenesis of lung cancer (LC). The polycomb repressive complex 2 (PRC2) is a conserved chromatin-associated complex that represses gene expression and is crucial for proper organismal development and gene expression patterns. Despite PRC2 dysregulation has been observed in various human cancers, the relationship between PRC2 genes variants and lung cancer risk remains largely unexplored.

Methods

To investigate the association between single nucleotide polymorphisms (SNPs) in PRC2 genes and the risk of developing LC, we genotyped blood genomic DNA from 270 LC patients and 452 healthy individuals of Chinese Han ethnicity using the TaqMan™ genotyping technique.

Results

We found that rs17171119T>G(adjusted odds ratio (OR) = 0.662, 95% CI: 0.467–0.938, P < 0.05), rs10898459 T>C(adjusted OR = 0.615, 95% CI: 0.4–0.947, P < 0.05), and rs1136258 C>T(adjusted OR = 0.273, 95% CI: 0.186–0.401, P < 0.001) were significantly associated with a reduced risk of LC. Stratified analysis revealed a protective effect of rs17171119 in both male and female patients, specifically those with lung adenocarcinoma (LUAD). Additionally, rs1391221 showed a protective effect in both the LUAD and lung squamous cell carcinoma (LUSC) groups, while rs1136258 exhibited a protective effect in both females and males, as well as in both LUAD and LUSC groups. Furthermore, analysis of The Cancer Genome Atlas (TCGA) dataset revealed expression levels of EED and RBBP4 in both LUAD and LUSC.

Conclusion

This study provides evidence that allelic variants in EZH2, EED, and RBBP4 may act as protective factors against LC development and could serve as genetic markers associated with susceptibility to LC.

Keywords:

• the polycomb repressive complex 2
• single nucleotide polymorphism
• lung cancer

Data Sharing Statement

All data needed to evaluate the conclusions of this study are presented in this article.

Ethics Approval and Consent to Participate

Our study was approved by the Institutional Ethics Committee of the General Hospital of Tianjin Medical University and the Institutional Ethics Committee of the Affiliated Hospital of Inner Mongolia Medical University. This study was conducted in accordance with the Declaration of Helsinki.

Author Contributions

SRK, JC, and HYL designed the research studies. MG, YWL, HH, LCS, and PJC performed the experiments. YGF, RFS, CC, XGL, GSZ, and DW analyzed data. MG, YWL, and HYL wrote the manuscript. JC provided financial support. SRK, YWL, and HYL supervised the project. All authors have jointly participated in the drafting, revision or critical review of the article and final approval of the version to be published. All authors were informed about the purpose of the study and have agreed on the journal to which the article is to be submitted and have agreed to take responsibility for all aspects of the work.

Disclosure

The authors have declared that no competing interest exists.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (82172569, 82072595, and 61973232), Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-061B and TJWJ2022XK005). Tianjin Health Science and Technology Project (ZC20179) and Beijing Science and Technology Innovation Medical Development Fund (KC2021-JX-0186-57).