Related Experiment Video
Updated: Feb 10, 2026
Modeling Spontaneous Metastatic Renal Cell Carcinoma mRCC in Mice Following Nephrectomy
Published on: April 29, 2014
ABCG2 Polymorphism rs2231142 and hypothyroidism in metastatic renal cell carcinoma patients treated with sunitinib
Emilie Werbrouck1, Julie Bastin1, Diether Lambrechts2,3
1a Department of General Medical Oncology , University Hospitals Leuven, Leuven Cancer Institute and Department of Oncology, KU Leuven , Leuven , Belgium.
Background And Aim:
Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) cause significant adverse events including thyroid dysfunction, mainly hypothyroidism, in a considerable proportion of patients. In a series of metastatic renal cell carcinoma (mRCC) patients treated with sunitinib, we aimed to study the correlation between hypothyroidism and single nucleotide polymorphisms (SNPs) in genes involved in sunitinib pharmacokinetics and pharmacodynamics.
Patients And Methods:
We included 79 mRCC patients who started sunitinib between November 2005 and March 2016. Serum thyroid function markers were collected at start and during sunitinib therapy. Germ-line DNA genotyping for 16 SNPs in 8 candidate genes was performed. Endpoints were time to increase in thyroid stimulating hormone (TSH) and time to decrease in T4 or free T4 (FT4) on day 1 and day 28 of each sunitinib cycle.
Results:
Patients with the ABCG2 rs2231142 CC-genotype had a significantly longer time-to-TSH-increase on day 1 (11 vs. 5 cycles; p = 0.0011), and time-to-T4/FT4-decrease on day 1 (not reached vs. 10 cycles; p = 0.013) and day 28 (28 vs. 7 cycles; p = 0.03) compared to CA-carriers. Patients with the CYP3A5 rs776746 GG-genotype had a significantly longer time-to-TSH-increase at day 1 compared to GA-patients: 11 vs. 5 cycles (p = 0.0071). Significant associations were also found between PDGFRA rs35597368 and rs1800812 and time-to-TSH-increase at day 28.
Conclusion:
Polymorphism rs2231142 in the efflux pump ABCG2 is associated with hypothyroidism in mRCC patients treated with sunitinib.
Insights
Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) like sunitinib can cause hypothyroidism. Genetic variations, specifically in ABCG2, are linked to this adverse event in metastatic renal cell carcinoma (mRCC) patients.
Area of Science:
- Pharmacogenomics
- Oncology
- Endocrinology
Background:
- Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) are associated with significant adverse events, notably hypothyroidism.
- Metastatic renal cell carcinoma (mRCC) patients treated with sunitinib frequently experience thyroid dysfunction.
Purpose of the Study:
- To investigate the correlation between hypothyroidism and single nucleotide polymorphisms (SNPs) in genes affecting sunitinib pharmacokinetics and pharmacodynamics.
- To identify genetic markers predicting hypothyroidism risk in mRCC patients undergoing sunitinib therapy.
Main Methods:
- A cohort of 79 mRCC patients treated with sunitinib was analyzed.
- Serum thyroid function markers (TSH, T4, FT4) were monitored throughout sunitinib therapy.
- Germ-line DNA was genotyped for 16 SNPs in 8 candidate genes.
Main Results:
- The ABCG2 rs2231142 CC-genotype was significantly associated with a delayed increase in TSH and decrease in T4/FT4 levels.
- CYP3A5 rs776746 GG-genotype showed a longer time to TSH increase at day 1.
- PDGFRA gene polymorphisms (rs35597368, rs1800812) were linked to delayed TSH increase at day 28.
Conclusions:
- Polymorphism rs2231142 in the ABCG2 gene is a significant predictor of hypothyroidism in mRCC patients treated with sunitinib.
- Genetic variations influence sunitinib-induced thyroid dysfunction, highlighting potential for personalized treatment strategies.
More Related Videos
05:36Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
06:38A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Related Concept Videos
01:05Single Nucleotide Polymorphisms-SNPs
01:17Factors Affecting Renal Clearance: Renal Impairment
One condition associated with renal failure is uremia. Uremia is characterized by impaired glomerular filtration and fluid accumulation in the body. This condition hinders the renal clearance of drugs, resulting in drug accumulation and potential...
01:21Factors Affecting Dissolution: Polymorphism, Amorphism and Pseudopolymorphism
Some polymorphic crystals possess lower aqueous solubility than their amorphous counterparts, leading to incomplete absorption. For instance, the oral suspension of Chloramphenicol, which...
01:20Renal Corpuscle
Glomerulus: Structure and Function
The glomerulus is a tiny, intricate network of capillaries located at the beginning of the nephron. It's enveloped by the Bowman's capsule and receives its blood supply from an afferent arteriole, which divides into numerous...
01:23Renal Clearance
Renal clearance refers to the volume of plasma cleared of a specific substance, such as creatinine, per unit of time. To measure clearance, urine samples are collected over a 24-hour period during each bladder voiding, followed by a single blood sample at the...
01:08Renal Drug Clearance: Comparison Between Renal Excretion Methods
Renal clearance is often associated with the renal glomerular filtration rate (GFR), which represents the rate at which plasma is filtered through the glomeruli in the kidney. When drug reabsorption is minimal and there is no active secretion, renal clearance is closely related to the...