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dc.contributor.authorAhern, Thomas P.en_US
dc.contributor.authorChristensen, Mariannen_US
dc.contributor.authorCronin-Fenton, Deirdre P.en_US
dc.contributor.authorLunetta, Kathryn L.en_US
dc.contributor.authorRosenberg, Carol L.en_US
dc.contributor.authorSørensen, Henrik Toften_US
dc.contributor.authorLash, Timothy L.en_US
dc.contributor.authorHamilton-Dutoit, Stephenen_US
dc.date.accessioned2011-12-29T21:02:25Z
dc.date.available2011-12-29T21:02:25Z
dc.date.issued2010-10-22
dc.identifier.citationAhern, 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)
dc.identifier.issn1179-1349
dc.identifier.urihttp://hdl.handle.net/2144/2534
dc.description.abstractOBJECTIVES: 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.sponsorshipUS 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.isoenen_US
dc.publisherDove Medical Pressen_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.subjectMolecular epidemiologyen_US
dc.subjectBreast neoplasmsen_US
dc.subjectCytochrome P450 CYP2D6en_US
dc.subjectGlucuronosyltransferaseen_US
dc.titleConcordance of Metabolic Enzyme Genotypes Assayed from Paraffin-Embedded, Formalin-Fixed Breast Tumors and Normal Lymphatic Tissueen_US
dc.typearticleen_US
dc.identifier.doi10.2147/CLEP.S13811
dc.identifier.pubmedid21152250
dc.identifier.pmcid2998813


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