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.

Interpreting the molecular mechanisms of RBBP4/7 and their roles in human diseases (Review)

“…RBBP4 is associated with genetic susceptibility to LC ( 84 ). Elevated RBBP4 expression in non-small cell LC (NSCLC) tissues amplifies cell proliferation and invasion, and is concomitantly linked to an adverse clinical outcome ( 13 , 84 ).…”

“…RBBP4 is associated with genetic susceptibility to LC ( 84 ). Elevated RBBP4 expression in non-small cell LC (NSCLC) tissues amplifies cell proliferation and invasion, and is concomitantly linked to an adverse clinical outcome ( 13 , 84 ). RBBP4 is also increased in cisplatin-resistant NSCLC, affecting drug resistance ( 85 ), and is associated with enhanced DNA damage sensitivity and repair pathway activity ( 86 ).…”