Gao Min, Li Yongwen, Huang Hua, Fan Yaguang, Shi Ruifeng, Su Lianchun, Chen Chen, Li Xuanguang, Zhu Guangsheng, Wu Di, Cao Peijun, Liu Hongyu, Chen Jun, Kang Shirong
Department of Thoracic Surgery, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot, 010010, People's Republic of China.
Inner Mongolia Medical University, Hohhot, 010010, People's Republic of China.
Onco Targets Ther. 2023 Jul 3;16:499-513. doi: 10.2147/OTT.S417190. eCollection 2023.
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.
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.
We found that rs17171119T>G(adjusted odds ratio (OR) = 0.662, 95% CI: 0.467-0.938, < 0.05), rs10898459 T>C(adjusted OR = 0.615, 95% CI: 0.4-0.947, < 0.05), and rs1136258 C>T(adjusted OR = 0.273, 95% CI: 0.186-0.401, < 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.
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.
遗传易感性在肺癌(LC)的发病机制中起很大作用。多梳抑制复合物2(PRC2)是一种保守的染色质相关复合物,可抑制基因表达,对生物体的正常发育和基因表达模式至关重要。尽管在各种人类癌症中都观察到PRC2失调,但PRC2基因变异与肺癌风险之间的关系在很大程度上仍未得到探索。
为了研究PRC2基因中的单核苷酸多态性(SNP)与患LC风险之间的关联,我们使用TaqMan™基因分型技术对270例LC患者和452例中国汉族健康个体的血液基因组DNA进行了基因分型。
我们发现rs17171119T>G(调整后的优势比(OR)=0.662,95%置信区间:0.467-0.938,P<0.05)、rs10898459 T>C(调整后的OR =0.615,95%置信区间:0.4-0.947,P<0.05)和rs1136258 C>T(调整后的OR =0.273,95%置信区间:0.186-0.401,P<0.001)与LC风险降低显著相关。分层分析显示,rs17171119对男性和女性患者,特别是肺腺癌(LUAD)患者具有保护作用。此外,rs1391221在LUAD和肺鳞状细胞癌(LUSC)组中均显示出保护作用,而rs1136258在女性和男性以及LUAD和LUSC组中均显示出保护作用。此外,对癌症基因组图谱(TCGA)数据集的分析揭示了EED和RBBP4在LUAD和LUSC中的表达水平。
本研究提供了证据表明,EZH2、EED和RBBP4中的等位基因变异可能作为预防LC发生的保护因素,并可作为与LC易感性相关的遗传标记。