Concordance of Metabolic Enzyme Genotypes Assayed from Paraffin-Embedded, Formalin-Fixed Breast Tumors and Normal Lymphatic Tissue

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dc.contributor.author Ahern, Thomas P en_US
dc.contributor.author Christensen, Mariann en_US
dc.contributor.author Cronin-Fenton, Deirdre P en_US
dc.contributor.author Lunetta, Kathryn L en_US
dc.contributor.author Rosenberg, Carol L en_US
dc.contributor.author Sørensen, Henrik Toft en_US
dc.contributor.author Lash, Timothy L en_US
dc.contributor.author Hamilton-Dutoit, Stephen en_US
dc.date.accessioned 2011-12-29T21:02:25Z
dc.date.available 2011-12-29T21:02:25Z
dc.date.issued 2010-10-22 en_US
dc.identifier.citation Ahern, Thomas P, Mariann Christensen, Deirdre P Cronin-Fenton, Kathryn L Lunetta, Carol L Rosenberg, Henrik Toft Sørensen, Timothy L Lash, Stephen Hamilton-Dutoit. "Concordance of metabolic enzyme genotypes assayed from paraffin-embedded, formalin-fixed breast tumors and normal lymphatic tissue" Clinical Epidemiology 2:241-246. (2010) en_US
dc.identifier.issn 1179-1349 en_US
dc.identifier.uri http://hdl.handle.net/2144/2534
dc.description.abstract OBJECTIVES: Translational epidemiology studies often use archived tumor specimens to evaluate genetic hypotheses involving cancer outcomes. When the exposure of interest is a germline polymorphism, a key concern is whether the genotype assayed from tumor-derived DNA is representative of the germline. We evaluated the concordance between breast tumor-derived and normal lymph node-derived genotypes for three polymorphic tamoxifen-metabolizing enzymes. METHODS. We assayed paired DNA samples extracted from archived tumor and normal lymph node tissues from 106 breast cancer patients. We used TaqMan assays to determine the genotypes of three enzyme variants hypothesized to modify tamoxifen effectiveness, ie, CYP2D6*4, UGT2B15*2, and UGT1A8*2. We assessed genotype agreement between the two DNA sources by calculating the percent agreement and the weighted kappa statistic. RESULTS: We successfully obtained genotypes for CYP2D6*4, UGT2B15*2, and UGT1A8*2 in 99%, 100%, and 84% of the paired samples, respectively. Genotype concordance was perfect for the CYP2D6*4 and UGT1A8*2 variants (weighted kappa for both = 1.00; 95% confidence interval [CI] 1.00, 1.00). For UGT2B15*2, one pair out of 106 gave a discordant result that persisted over several assay repeats. CONCLUSIONS: We observed strong agreement between DNA from breast tumors and normal lymphatic tissue in the genotyping of polymorphisms in three tamoxifen-metabolizing enzymes. Genotyping DNA extracted from tumor tissue avoids the time-consuming practice of microdissecting adjacent normal tissue when other normal tissue sources are not available. Therefore, the demonstrated reliability of tumor-derived DNA allows resources to be spent instead on increasing sample size or the number of polymorphisms examined. en_US
dc.description.sponsorship US National Cancer Institute (R01 CA118708); Danish Cancer Society (DP06117); Karen Elise Jensen Foundation; Congressional Directed Medical Research Programs predoctoral training award (BC073012) en_US
dc.language.iso en en_US
dc.publisher Dove Medical Press en_US
dc.rights © 2010 Ahern et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. en_US
dc.subject Molecular epidemiology en_US
dc.subject Breast neoplasms en_US
dc.subject Cytochrome P450 CYP2D6 en_US
dc.subject Glucuronosyltransferase en_US
dc.title Concordance of Metabolic Enzyme Genotypes Assayed from Paraffin-Embedded, Formalin-Fixed Breast Tumors and Normal Lymphatic Tissue en_US
dc.type article en_US
dc.identifier.doi 10.2147/CLEP.S13811 en_US
dc.identifier.pubmedid 21152250 en_US
dc.identifier.pmcid 2998813 en_US

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