ArticleGenome biology2019
The inherited variations of a p53-responsive enhancer in 13q12.12 confer lung cancer risk by attenuating TNFRSF19 expression.
Article in Genome biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 of them syntheses that pooled it.
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Who cites it
23 citing papers in PubMed, 2 syntheses or guidelines pooled it, 36 citations in OpenAlex.
- The landscape of GWAS validation; systematic review identifying 309 validated non-coding variants across 130 human diseases.BMC medical genomics · 2022Pooled it
- Identification of a costimulatory molecule-based signature for predicting prognosis risk and immunotherapy response in patients with lung adenocarcinoma.Oncoimmunology · 2020Pooled it
- Novel multi-omic biomarkers to combat oocyte and ovarian aging.GeroScience · 2026Article
- Role of tumor necrosis factor receptor superfamily member 19 in cancer: Diverse functions and therapeutic potential (Review).Oncology letters · 2026Review
- Unveiling TNFRSF19: a novel tumor suppressor targeting endoplasmic reticulum stress and LGR5/Wnt/β-catenin in cervical cancer.Human cell · 2026Article
- Observational
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- 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
- The role of tumor necrosis factor receptor superfamily in cancer: insights into oncogenesis, progression, and therapeutic strategies.NPJ precision oncology · 2025Review
- Massively parallel variant-to-function mapping determines functional regulatory variants of non-small cell lung cancer.Nature communications · 2025Article
- 1p-Enh-regulated CYP4B1 alleviates NNK-induced heart failure and lung cancer via the STAT3 pathway.PloS one · 2025Article
- Single nucleotide variants in lung cancer.Chinese medical journal pulmonary and critical care medicine · 2024Review
- TNFRSF19 promotes endoplasmic reticulum stress-induced paraptosis via the activation of the MAPK pathway in triple-negative breast cancer cells.Cancer gene therapy · 2024Article
- Significance ofInternational journal of medical sciences · 2024Article
- Radiogenomics: a key component of precision cancer medicine.British journal of cancer · 2023Review
- A Novel apaQTL-SNP for the Modification of Non-Small-Cell Lung Cancer Susceptibility across Histological Subtypes.Cancers · 2022Article
- The Association ofJournal of Cancer · 2022Article
- The Polymorphism and Expression of EGFL7 and miR-126 Are Associated With NSCLC Susceptibility.Frontiers in oncology · 2022Article
- Systematic evaluation of the effect of polyadenylation signal variants on the expression of disease-associated genes.Genome research · 2021Article
- Associations BetweenFrontiers in oncology · 2021Article
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Authors and funding
20 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInherited factors contribute to lung cancer risk, but the mechanism is not well understood. Defining the biological consequence of GWAS hits in cancers is a promising strategy to elucidate the inherited mechanisms of cancers. The tag-SNP rs753955 (A>G) in 13q12.12 is highly associated with lung cancer risk in the Chinese population. Here, we systematically investigate the biological significance and the underlying mechanism behind 13q12.12 risk locus in vitro and in vivo.
resultsWe characterize a novel p53-responsive enhancer with lung tissue cell specificity in a 49-kb high linkage disequilibrium block of rs753955. This enhancer harbors 3 highly linked common inherited variations (rs17336602, rs4770489, and rs34354770) and six p53 binding sequences either close to or located between the variations. The enhancer effectively protects normal lung cell lines against pulmonary carcinogen NNK-induced DNA damages and malignant transformation by upregulating TNFRSF19 through chromatin looping. These variations significantly weaken the enhancer activity by affecting its p53 response, especially when cells are exposed to NNK. The effect of the mutant enhancer alleles on TNFRSF19 target gene in vivo is supported by expression quantitative trait loci analysis of 117 Chinese NSCLC samples and GTEx data. Differentiated expression of TNFRSF19 and its statistical significant correlation with tumor TNM staging and patient survival indicate a suppressor role of TNFRSF19 in lung cancer.
conclusionThis study provides evidence of how the inherited variations in 13q12.12 contribute to lung cancer risk, highlighting the protective roles of the p53-responsive enhancer-mediated TNFRSF19 activation in lung cells under carcinogen stress.
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