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Åke Borg

Åke Borg

Principal investigator

Åke Borg

Functional characterization of a multi-cancer risk locus on chr5p15.33 reveals regulation of TERT by ZNF148


  • Jun Fang
  • Laufey T. Amundadottir

Other contributions

  • Christian Ingvar
  • Håkan Olsson
  • Göran Jönsson
  • Åke Borg
  • Katja Harbst
  • Kari Nielsen
  • Anita Schmidt Zander

Summary, in English

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.


  • Lund Melanoma Study Group
  • Surgery (Lund)
  • Tumor microenvironment
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
  • EpiHealth: Epidemiology for Health
  • Medical oncology
  • Melanoma Genomics
  • Breastcancer-genetics
  • Familial Breast Cancer
  • Dermatology and Venereology (Lund)
  • Clinical Sciences, Helsingborg

Publishing year





Nature Communications



Document type

Journal article


Nature Publishing Group


  • Medical Genetics



Research group

  • Lund Melanoma Study Group
  • Melanoma Genomics
  • Familial Breast Cancer


  • ISSN: 2041-1723