Alternative polyadenylation-related genetic variants contribute to bladder cancer risk
Ting Liu1
Jingjing Gu1
Chuning Li1
Mengfan Guo1
Lin Yuan2
Qiang Lv3
Chao Qin3
Mulong Du1
Haiyan Chu1
Hanting Liu1
Zhengdong Zhang1
1.Department of Environmental Genomics,Jiangsu Key Laboratory of Cancer Biomarkers,Prevention and Treatment,Collaborative Innovation Center for Cancer Personalized Medicine,School of Public Health,Nanjing Medical University,Nanjing,Jiangsu 211166,China;Department of Genetic Toxicology,the Key Laboratory of Modern Toxicology of Ministry of Education,Center for Global Health,School of Public Health,Nanjing Medical University,Nanjing,Jiangsu 211166,China2.Department of Urology,Jiangsu Province Hospital of Traditional Chinese Medicine,Nanjing,Jiangsu 210029,China3.Department of Urology,the First Affiliated Hospital of Nanjing Medical University,Nanjing,Jiangsu 210029,China
摘要：Aberrant alternative polyadenylation(APA)events play an important role in cancers,but little is known about whether APA-related genetic variants contribute to the susceptibility to bladder cancer.Previous genome-wide association study performed APA quantitative trait loci(apaQTL)analyses in bladder cancer,and identified 17 955 single nucleotide polymorphisms(SNPs).We found that gene symbols of APA affected by apaQTL-associated SNPs were closely correlated with cancer signaling pathways,high mutational burden,and immune infiltration.Association analysis showed that apaQTL-associated SNPs rs34402449 C>A,rs2683524 C>T,and rs11540872 C>G were significantly associated with susceptibility to bladder cancer(rs34402449:OR=1.355,95%confidence interval[CI]:1.159-1.583,P=1.33×10-4;rs2683524:OR=1.378,95%CI:1.164-1.632,P=2.03×10-4;rs11540872:OR=1.472,95%CI:1.193-1.815,P=3.06×10-4).Cumulative effect analysis showed that the number of risk genotypes and smoking status were significantly associated with an increased risk of bladder cancer(Ptrend=2.87×10-12).We found that PRR13,being demonstrated the most significant effect on cell proliferation in bladder cancer cell lines,was more highly expressed in bladder cancer tissues than in adjacent normal tissues.Moreover,the rs2683524 T allele was correlated with shorter 3′ untranslated regions of PRR13 and increased PRR13 expression levels.Collectively,our findings have provided informative apaQTL resources and insights into the regulatory mechanisms linking apaQTL-associated variants to bladder cancer risk.
机标关键词：alternativegeneticcancerriskbladdercontributepolyadenylationrelated
分类号：R737.14(泌尿生殖器肿瘤)
论文发表日期：2023-11-30
在线出版日期：2026-03-31（本平台首次上网日期，不代表文献的发表时间）
页数：14( 前插1,405-417 )
英文信息