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Screening for Functional Non-coding Genetic Variants Using Electrophoretic Mobility Shift Assay (EMSA) and DNA-affinity Precipitation Assay (DAPA)
Published on: August 21, 2016
Genome-wide meta-analysis identifies variants associated with platinating agent susceptibility across populations
H E Wheeler1, E R Gamazon, A L Stark
1Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
The Pharmacogenomics Journal
|August 17, 2011
Summary
Genetic variations influence how patients respond to platinum-based chemotherapy. This study identified key single-nucleotide polymorphisms (SNPs) associated with carboplatin and cisplatin drug response, offering potential for personalized cancer treatment strategies.
Area of Science:
- Pharmacogenomics
- Cancer Therapeutics
- Genetics
Background:
- Platinum-based chemotherapy agents, such as carboplatin and cisplatin, are vital cancer treatments.
- However, their effectiveness is often limited by drug-induced toxicities and the development of treatment resistance.
- Identifying genetic factors influencing patient response is crucial for optimizing therapy.
Purpose of the Study:
- To conduct meta-analyses of genetic variations, specifically single-nucleotide polymorphisms (SNPs), associated with carboplatin- and cisplatin-induced cytotoxicity.
- To identify novel genetic markers and confirm previously implicated genes in platinum-based drug response.
Main Methods:
- Meta-analysis of over 3 million single-nucleotide polymorphisms (SNPs) across 608 lymphoblastoid cell lines (LCLs) from diverse global populations.
- Analysis focused on cytotoxicity induced by carboplatin and cisplatin.
Main Results:
- The most significant SNP for carboplatin response was found in an intron of the NBAS gene.
- The most significant SNP for cisplatin response was identified upstream of the KRT16P2 gene.
- SNPs associated with cisplatin susceptibility were also enriched for carboplatin susceptibility, and identified variants are polymorphic across diverse populations.
Conclusions:
- Genetic variants in NBAS and KRT16P2 are significantly associated with carboplatin and cisplatin cytotoxicity, respectively.
- The overlap in susceptibility SNPs suggests shared genetic mechanisms in response to platinum agents.
- These findings highlight the potential for pharmacogenomic testing to guide personalized platinum-based cancer therapy.
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