Genotyping panel for assessing response to cancer chemotherapy

Zunyan Dai^*¹^,2 , Audrey C Papp^*¹ , Danxin Wang^*¹ , Heather Hampel³ and Wolfgang Sadee¹

¹Program in Pharmacogenomics, Department of Pharmacology, Comprehensive Cancer Center, College of Medicine and Public Health, The Ohio State University, 5072 Graves Hall, 333 West 10th Avenue, Columbus, OH 43210-1239, USA

²Department of Pathology, College of Medicine and Public Health, The Ohio State University, 680 Ackerman Road, Columbus, Ohio 43202, USA

³Division of Human Genetics, College of Medicine and Public Health, The Ohio State University, 2050 Kenny Road, 8th floor tower, Columbus, OH 43221, USA

author email corresponding author email* Contributed equally

BMC Medical Genomics 2008, 1:24doi:10.1186/1755-8794-1-24


Published:	11 June 2008

Abstract

Background

Variants in numerous genes are thought to affect the success or failure of cancer chemotherapy. Interindividual variability can result from genes involved in drug metabolism and transport, drug targets (receptors, enzymes, etc), and proteins relevant to cell survival (e.g., cell cycle, DNA repair, and apoptosis). The purpose of the current study is to establish a flexible, cost-effective, high-throughput genotyping platform for candidate genes involved in chemoresistance and -sensitivity, and treatment outcomes.

Methods

We have adopted SNPlex for genotyping 432 single nucleotide polymorphisms (SNPs) in 160 candidate genes implicated in response to anticancer chemotherapy.

Results

The genotyping panels were applied to 39 patients with chronic lymphocytic leukemia undergoing flavopiridol chemotherapy, and 90 patients with colorectal cancer. 408 SNPs (94%) produced successful genotyping results. Additional genotyping methods were established for polymorphisms undetectable by SNPlex, including multiplexed SNaPshot for CYP2D6 SNPs, and PCR amplification with fluorescently labeled primers for the UGT1A1 promoter (TA)nTAA repeat polymorphism.

Conclusion

This genotyping panel is useful for supporting clinical anticancer drug trials to identify polymorphisms that contribute to interindividual variability in drug response. Availability of population genetic data across multiple studies has the potential to yield genetic biomarkers for optimizing anticancer therapy.