Correlation Between Single Nucleotide Polymorphisms Of PRC2 Complex And Susceptibility Of Lung Cancer In Chinese Population

Objective:Lung cancer is currently the leading cause of cancer-related death worldwide,with more than 2 million people newly diagnosed each year according to global cancer statistics.Polycomb repressive complex 2（PRC2）is a conserved inhibitory chromatin-associated complex that plays a key role in ensuring proper gene silencing,which is essential for maintaining organism development and gene expression patterns.The study found that the PRC2 complex is deregulated in a variety of human cancers,however,the relationship between genetic variation in the PRC2 complex and lung cancer risk remains largely unknown.The purpose of this study was to investigate the genetic correlation between single nucleotide polymorphisms（SNPs）of PRC2 complex and primary lung cancer.Methods:A total of 270 lung cancer patients and 452 healthy controls were included in this study.The lung cancer patients were diagnosed by pathology,the control group was all healthy physical examiners,and all the study subjects were Han Chinese.After obtaining the informed consent of all the research subjects in the lung cancer patient group and the healthy control group,5ml of peripheral venous blood was drawn from each other,and the genomic DNA of all the study subjects was extracted by the blood genome extraction kit（centrifuge column type）,and the blood genomic DNA of the research subjects was genotyped by TaqMan^TMgenotyping technology to explore the relationship between lung cancer risk and PRC2 SNPs.In this study,10 SNP sites of four genes in the PRC2 complex were selected:EZH2（rs1880357,rs3757441,rs17171119）,EED（rs1391221,rs7952481,rs10898459）,SUZ12（rs578635,rs508192）and RBBP4（rs1136258,rs12407673）.Taqman-MGB probe technology was used to genotype the sites selected in this study,processed and entered the data,and the goodness-of-fitχ²test was used to analyze whether the genotype distribution of SNPs of genes in the PRC2 complex in the control group was in accordance with Hardy-Weinberg equilibrium（HWE）to detect whether the subjects included in the study were population representative,P>0.05 was considered to be consistent HWE.SPSS 24.0 software was used for statistical analysis,and logistic regression was used to analyze the relationship between genetic polymorphisms of PRC2 complex and primary lung cancer.Meaningful sited were further stratified according to the age,sex,and pathological type of the study subjects.The linkage disequilibrium and haplotype analysis of each gene site were analyzed,and the P<0.05 was considered to be statistically significant.We also analyzed tumor data from the Cancer Genome Atlas（TCGA）.Results:1.Among the 10 SNP sites selected in this study,except rs17171119 and rs1391221,all other sites conform to the HWE.2.This study showed a correlation between single nucleotide polymorphisms of the PRC2 complex and susceptibility to lung cancer.The results of logistic regression analysis showed that the distribution frequency of the two sites of the EZH2 gene（rs1880357 and rs3757441）in the case group and the control group was not statistically significant.Compared with the GG genotype,the CC genotype at the rs1391221 site of the EED gene significantly increased the risk of lung cancer（adjusted OR=3.268,95%CI=1.005-10.630,P<0.05）,and the TC genotype at the rs10898459 site had a protective effect in the development of lung cancer（adjusted OR=0.615,95%CI=0.400-0.947,P<0.05）.There was no significant difference in the allele frequency distribution of rs578635 and rs508192 sites in the SUZ12gene in the case group and control group（P<0.05）;the difference in allele frequency distribution at rs12407673 site of the RBBP4 gene was not statistically significant between the case group and the control group（P<0.05）,while the difference in the distribution of rs1136258 site was statistically significant,and the variant genotype reduced the risk of lung cancer（P<0.05）。3.Stratified analysis showed that compared with healthy control groups,the mutation rate of rs1391221 of EED gene and rs1136258 of RBBP4 gene in lung cancer patients was significantly reduced.4.The results of gene linkage disequilibrium analysis showed that there was a high linkage disequilibrium in the rs508192 and rs578635 sites of the SUZ12 gene（D’=1,r²=0.009）.There is also some linkage disequilibrium between the rs12407673 and rs1136258sites of the RBBP4 gene（D’=0.672,r²=0.176）.5.Haplotype analysis showed that the risk of lung cancer was significantly increased in the population with haplotype C（rs1391221）T（rs10898459）in the EED gene（adjusted OR=2.647,95%CI=2.647-4.552,P<0.05）.The distribution of haplotypes C（rs1136258）T（rs12407673）（adjusted OR=0.033,95%CI=0.012-0.088,P<0.05）and T（rs1136258）C（rs12407673）（adjusted OR=0.379,95%CI=0.23-0.624,P<0.05）in the RBBP4 gene was significantly different between the case and control groups.And these two haplotypes have a protective effect on the occurrence of lung cancer.6.The results of TCGA database analysis showed that the expression levels of EZH2,EED,and RBBP4 genes in lung adenocarcinoma and lung squamous cell carcinoma tissues were significantly higher than those in adjacent tissues,and patients with high expression had worse prognosis than patients with low expression of EZH2 and RBBP4 genes.Conclusion The results of this study show that single nucleotide polymorphisms of the PRC2 complex are associated with genetic susceptibility to lung cancer in Chinese groups.The rs10898459 and rs1391221 sites of the EED gene and the mutant allele in the rs1136258locus of the RBBP4 gene may be protective factors for lung cancer development and may be markers associated with genetic susceptibility to lung cancer.