ArticleNature communications2017
Functional characterization of a multi-cancer risk locus on chr5p15.33 reveals regulation of TERT by ZNF148.
Erratum issuedOpen access · goldAbstract read
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Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 41 papers, 2 of them syntheses that pooled it.
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41citing papers in PubMed, 2 pooled it
2.8field-weighted citation impact, top 10% of its field
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Who cites it
41 citing papers in PubMed, 2 syntheses or guidelines pooled it, 53 citations in OpenAlex.
- A genome-wide association study of buccal mucosa cancer in India and multi-ancestry meta-analysis discovers risk loci and gene-environment interactions.EBioMedicine · 2025Pooled it
- The landscape of GWAS validation; systematic review identifying 309 validated non-coding variants across 130 human diseases.BMC medical genomics · 2022Pooled it
- Prioritizing context-specific genetic risk mechanisms in 11 solid cancers.Journal of the National Cancer Institute · 2026Article
- Review
- Mapping Genetic Regulation of Transcription to Identify Functional Variants and Genes Associated with Pancreatic Cancer Risk.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Characterization of a pancreatic cancer GWAS signal suggests PDX1 buffers stress in the exocrine pancreas.medRxiv : the preprint server for health sciences · 2026Article
- A Large-Scale Method to Measure the Stoichiometries of Protein Poly-ADP-Ribosylation.ACS chemical biology · 2026Article
- Integrative screening identifies functional variants and VNTRs underlying GWAS signals at the 5p15.33 multi-cancer susceptibility locus.medRxiv : the preprint server for health sciences · 2026Article
- Article
- The Testicular Cancer Consortium (TECAC): Filling Knowledge Gaps in the Genetic Etiology of Testicular Germ Cell Tumors.Andrology · 2026Article
- Transcriptomic Profile of Isocitrate Dehydrogenase Mutant Type of Lower-Grade Glioma Reveals Molecular Changes for Prognosis.Biomedicines · 2025Article
- p63 and ZNF148 cooperate to regulate head and neck squamous cell carcinoma.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Allelic effects on KLHL17 expression underlie a pancreatic cancer genome-wide association signal at chr1p36.33.Nature communications · 2025Article
- Functional analysis of cancer-associated germline risk variants.Nature genetics · 2025Article
- Massively parallel variant-to-function mapping determines functional regulatory variants of non-small cell lung cancer.Nature communications · 2025Article
- ZNF740 facilitates the malignant progression of hepatocellular carcinoma via the METTL3/HIF‑1A signaling axis.International journal of oncology · 2024Article
- Upregulation of the ZNF148/PTX3 axis promotes malignant transformation of dendritic cells in glioma stem-like cells microenvironment.CNS neuroscience & therapeutics · 2023Article
- Functional characterization of 5p15.33 risk locus in uveal melanoma reveals rs452384 as a functional variant and NKX2.4 as an allele-specific interactor.American journal of human genetics · 2022Article
- Pancreatic Tumorigenesis: Precursors, Genetic Risk Factors and Screening.Current oncology (Toronto, Ont.) · 2022Review
- Functional studies of lung cancer GWAS beyond association.Human molecular genetics · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
44 authors at 20 institutions in 19 countries.
Jun FangLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Jinping JiaLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Matthew MakowskiLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Mai XuLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Zhaoming WangDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Tongwu ZhangLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Jason W HoskinsLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Jiyeon ChoiLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Younghun HanDepartment of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Lebanon, New Hampshire 03756, USA.
Mingfeng ZhangLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Janelle ThomasLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Michael KovacsLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Irene CollinsLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Marta DzyadykLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Abbey ThompsonLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Maura O'NeillProtein Characterization Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland 21701, USA.
Sudipto DasProtein Characterization Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland 21701, USA.
Qi LanLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Roelof KosterLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.ORCID 0000-0003-1424-8579
PanScan Consortium
TRICL Consortium
GenoMEL Consortium
Rachael S Stolzenberg-SolomonDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Peter KraftDepartment of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Brian M WolpinDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
Pascal W T C JansenDepartment of Molecular Biology, Radboud Institute for Molecular Life Sciences, Radboud University, Nijmegen 6500 HB, The Netherlands.
Sara OlsonDepartment of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York City, New York 10065, USA.
Katherine A McGlynnDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Peter A KanetskyDepartment of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA.
Nilanjan ChatterjeeDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Jennifer H BarrettSection of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds LS9 7TF, UK.
Alison M DunningDepartment of Oncology, University of Cambridge, Cambridge CB2 0XZ, UK.
John C TaylorSection of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds LS9 7TF, UK.
Julia A Newton-BishopSection of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds LS9 7TF, UK.
D Timothy BishopSection of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds LS9 7TF, UK.ORCID 0000-0002-8752-8785
Thorkell AndressonProtein Characterization Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland 21701, USA.
Gloria M PetersenDepartment of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905, USA.
Christopher I AmosDepartment of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Lebanon, New Hampshire 03756, USA.
Mark M IlesSection of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds LS9 7TF, UK.
Katherine L NathansonTranslational Medicine and Human Genetics, Department of Medicine and Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.ORCID 0000-0002-6740-0901
Maria Teresa LandiDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Michiel VermeulenDepartment of Molecular Biology, Radboud Institute for Molecular Life Sciences, Radboud University, Nijmegen 6500 HB, The Netherlands.
Kevin M BrownLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Laufey T AmundadottirLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
National Institutes of Health · USHospital Clínic de Barcelona · ESMacquarie University · AUSheba Medical Center · ILUniversity of Leeds · GBBrigham and Women's Hospital · USUniversité Paris-Saclay · FRNetherlands Consortium for Healthy Ageing · NLUniversity of Milan · ITInstitute of Cancer Research · GBInstitute of Oncology Ljubljana · SILeiden University Medical Center · NLRadboud University Nijmegen · NLThe University of Queensland · AUAmerican Cancer Society · USCentre international de recherche sur le cancer · FRFrederick National Laboratory for Cancer Research · USFred Hutch Cancer Center · USGerman Cancer Research Center · DEInserm · FR
Funding
Translational Engineering in Cancer (TEC)P30CA023108 · NCI · DARTMOUTH COLLEGE · PI Steven D Leach · 1985 to 2026
$91.3MTumor Antigens for Individual Signatures and TherapyP50CA062924 · NCI · JOHNS HOPKINS UNIVERSITY · PI LENNON, ANNE MARIE · 1993 to 2022
$54.6MPost GWA Studies in Testicular Germ Cell TumorsU01CA164947 · NCI · UNIVERSITY OF PENNSYLVANIA · PI KANETSKY, PETER A, NATHANSON, KATHERINE L. · 2012 to 2024
$11.7MValidation and Fine-Scale Mapping of Pancreatic Cancer Susceptibility Loci (Study)R01CA154823 · NCI · JOHNS HOPKINS UNIVERSITY · PI KLEIN, ALISON P · 2011 to 2020
$5.7MThe NYU Women's Health StudyUM1CA182934 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ZELENIUCH-JAQUOTTE, ANNE · 2015 to 2019
$3.7MINFRASRUCTURE SUPPORT AND DATA ENHANCEMENTS FOR THE CARET BIOREPOSITORYUM1CA167462 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI GOODMAN, GARY E · 2013 to 2017
$2.8MCancer Research UK 10589Cancer Research UK 14136Cancer Research UK 19167Medical Research Council G0401527Medical Research Council G1000143Medical Research Council MR/N003284/1NCI NIH HHS P30 CA023108NCI NIH HHS P50 CA062924NCI NIH HHS R01 CA154823NCI NIH HHS U01 CA164947NCI NIH HHS UM1 CA167462NCI NIH HHS UM1 CA182934
Abstract
Genome wide association studies (GWAS) have mapped multiple independent cancer susceptibility loci to chr5p15.33. Here, we show that fine-mapping of pancreatic and testicular cancer GWAS within one of these loci (Region 2 in CLPTM1L) focuses the signal to nine highly correlated SNPs. Of these, rs36115365-C associated with increased pancreatic and testicular but decreased lung cancer and melanoma risk, and exhibited preferred protein-binding and enhanced regulatory activity. Transcriptional gene silencing of this regulatory element repressed TERT expression in an allele-specific manner. Proteomic analysis identifies allele-preferred binding of Zinc finger protein 148 (ZNF148) to rs36115365-C, further supported by binding of purified recombinant ZNF148. Knockdown of ZNF148 results in reduced TERT expression, telomerase activity and telomere length. Our results indicate that the association with chr5p15.33-Region 2 may be explained by rs36115365, a variant influencing TERT expression via ZNF148 in a manner consistent with elevated TERT in carriers of the C allele.
Indexed as
Gene Expression Regulation, NeoplasticAllelesCell Line, TumorChromosome MappingChromosomes, Human, Pair 5DNA-Binding ProteinsFemaleGenetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyHistonesHumansLung NeoplasmsMaleMelanomaPancreatic NeoplasmsDNA-Binding ProteinsHistonesRNA, Small InterferingTelomeraseTERT protein, humanTranscription FactorsZNF148 protein, human
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