Related Experiment Video
Updated: Feb 26, 2026
06:21
Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer
Published on: May 10, 2024
1.3K
Multiple renal cancer susceptibility polymorphisms modulate the HIF pathway.
Steffen Grampp1, Virginia Schmid2, Rafik Salama2
1Department of Nephrology and Hypertension, Universitätsklinikum Erlangen und Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
Plos Genetics
|July 18, 2017
Summary
Genetic variations near hypoxia-inducible factor (HIF) binding sites significantly increase renal cell cancer (RCC) risk. A specific polymorphism creates a new HIF binding site, upregulating BHLHE41 and driving cancer development.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Hypoxia-inducible factor (HIF) activation is common in renal cell cancer (RCC).
- The precise role of genetic variations in HIF pathway dysregulation in RCC development remains unclear.
Purpose of the Study:
- To investigate the impact of genetic susceptibility loci on HIF pathway activity in RCC.
- To elucidate the mechanistic link between RCC-associated polymorphisms and HIF target gene regulation.
Main Methods:
- Genome-wide analysis of HIF-binding sites.
- Alignment with human RCC-susceptibility polymorphisms.
- Allele-specific assays for HIF binding, chromatin conformation, and gene expression.
- eQTL analyses in human tumors.
Main Results:
- Significant overlap observed between RCC-susceptibility polymorphisms and HIF-binding sites.
- Identified a novel mechanism at chromosome 12p12.1 involving the risk polymorphism rs12814794.
- This polymorphism creates a new HIF-binding site, leading to HIF-1α-specific upregulation of BHLHE41.
Conclusions:
- Genetic variations within the HIF cis-regulatory apparatus significantly influence RCC development.
- Minor genetic variations in this pathway can have substantial effects on cancer risk.
Related Concept Videos
03:03mTOR Signaling and Cancer Progression
4.9K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
4.9K
01:24Regulation of Angiogenesis and Blood Supply
3.8K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.8K
01:29Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
57
Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
57
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
51
Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
51
02:53Adaptive Mechanisms in Cancer Cells
7.2K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
7.2K
01:33Cancer-Critical Genes I: Proto-oncogenes
11.6K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
11.6K