ArticleNPJ precision oncology2022
Deciphering associations between three RNA splicing-related genetic variants and lung cancer risk.
Article in NPJ precision oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.
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Who cites it
6 citing papers in PubMed, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.
- Multi-ancestry GWAS meta-analyses of lung cancer reveal susceptibility loci and elucidate smoking-independent genetic risk.Nature communications · 2024Pooled it
- Integrated genetic and epigenetic analysis identifies that rs939408 affects non-smoking lung adenocarcinoma risk by modulating the DNA methylation of LRRC2.Cell death & disease · 2025Article
- Identification of novel pQTL-SNPs associated with lung adenocarcinoma risk: A multi-stage study.Cancer medicine · 2024Article
- Integrating apaQTL and eQTL analysis identifies a potential causal variant associated with lung adenocarcinoma risk in the Chinese population.Communications biology · 2024Article
- An Analysis of JADE2 in Non-Small Cell Lung Cancer (NSCLC).Biomedicines · 2023Article
- Development and validation of a N6 methylation regulator-related gene signature for prognostic and immune response prediction in non-small cell lung cancer.American journal of cancer research · 2023Article
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Authors and funding
21 authors at 13 institutions in 8 countries.
Funding
Abstract
Limited efforts have been made in assessing the effect of genome-wide profiling of RNA splicing-related variation on lung cancer risk. In the present study, we first identified RNA splicing-related genetic variants linked to lung cancer in a genome-wide profiling analysis and then conducted a two-stage (discovery and replication) association study in populations of European ancestry. Discovery and validation were conducted sequentially with a total of 29,266 cases and 56,450 controls from both the Transdisciplinary Research in Cancer of the Lung and the International Lung Cancer Consortium as well as the OncoArray database. For those variants identified as significant in the two datasets, we further performed stratified analyses by smoking status and histological type and investigated their effects on gene expression and potential regulatory mechanisms. We identified three genetic variants significantly associated with lung cancer risk: rs329118 in JADE2 (P = 8.80E-09), rs2285521 in GGA2 (P = 4.43E-08), and rs198459 in MYRF (P = 1.60E-06). The combined effects of all three SNPs were more evident in lung squamous cell carcinomas (P = 1.81E-08, P = 6.21E-08, and P = 7.93E-04, respectively) than in lung adenocarcinomas and in ever smokers (P = 9.80E-05, P = 2.70E-04, and P = 2.90E-05, respectively) than in never smokers. Gene expression quantitative trait analysis suggested a role for the SNPs in regulating transcriptional expression of the corresponding target genes. In conclusion, we report that three RNA splicing-related genetic variants contribute to lung cancer susceptibility in European populations. However, additional validation is needed, and specific splicing mechanisms of the target genes underlying the observed associations also warrants further exploration.
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