Multiple renal cancer susceptibility polymorphisms modulate the HIF pathway

Journal article

Publication Details

Author(s): Grampp S, Schmid V, Salama R, Lauer V, Kranz F, Platt JL, Smythies J, Choudhry H, Goppelt-Strübe M, Ratcliffe PJ, Mole DR, Schoedel J
Journal: Plos Genetics
Publication year: 2017
Volume: 13
Pages range: e1006872
ISSN: 1553-7390
eISSN: 1553-7404
Language: English


Un-physiological activation of hypoxia inducible factor (HIF) is an early event in most renal cell cancers (RCC) following inactivation of the von Hippel-Lindau tumor suppressor. Despite intense study, how this impinges on cancer development is incompletely understood. To test for the impact of genetic signals on this pathway, we aligned human RCC-susceptibility polymorphisms with genome-wide assays of HIF-binding and observed highly significant overlap. Allele-specific assays of HIF binding, chromatin conformation and gene expression together with eQTL analyses in human tumors were applied to mechanistic analysis of one such overlapping site at chromosome 12p12.1. This defined a novel stage-specific mechanism in which the risk polymorphism, rs12814794, directly creates a new HIF-binding site that mediates HIF-1? isoform specific upregulation of its target BHLHE41. The alignment of multiple sites in the HIF cis-acting apparatus with RCC-susceptibility polymorphisms strongly supports a causal model in which minor variation in this pathway exerts significant effects on RCC development.

FAU Authors / FAU Editors

Goppelt-Strübe, Margarete apl. Prof. Dr.
Medizinische Klinik 4 - Nephrologie und Hypertensiologie
Kranz, Franziska
Lehrstuhl für Informatik 9 (Graphische Datenverarbeitung)
Lauer, Victoria Dr. rer. nat.
Medizinische Klinik 4 - Nephrologie und Hypertensiologie

External institutions with authors

King Abdulaziz University (KAU) / جامعة الملك عبد العزيز
University of Oxford

How to cite

Grampp, S., Schmid, V., Salama, R., Lauer, V., Kranz, F., Platt, J.L.,... Schoedel, J. (2017). Multiple renal cancer susceptibility polymorphisms modulate the HIF pathway. Plos Genetics, 13, e1006872.

Grampp, Steffen, et al. "Multiple renal cancer susceptibility polymorphisms modulate the HIF pathway." Plos Genetics 13 (2017): e1006872.


Last updated on 2019-06-03 at 11:53