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Concordance of pharmacogenetic markers in germline and colorectal tumor DNA.

INTRODUCTION
Most cancer pharmacogenetic studies use germline DNA, as tumor tissue is often inaccessible in the advanced disease setting. However, this relies on the assumption that germline DNA is representative of the tumor genotype. To date, there has been little attention paid to defining the relationship between tumor and germline genomes.


MATERIALS AND METHODS
This study compared 28 polymorphisms in 13 genes of high importance to cancer pharmacogenetics from ten different chromosome regions, in DNA from normal mucosa and colon tumors in 44 paired samples.


RESULTS
93% of samples had one or fewer genotype discrepancies. 77% of patients had intraindividual genotypes in complete concordance. In addition, although microsatellite instability (MSI) was identified in 20% of tumors, no significant association between MSI and genotype discrepancies was observed (p = 0.672).


CONCLUSIONS
While this data validates the use of germline DNA pharmacogenetics in colorectal cancer, statistical analysis and modeling of pharmacogenetic data should be employed to incorporate this small, but important, source of error.