CYP2D6 genotyping and use of antidepressants in breast cancer patients : test development for clinical application

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dc.contributor.authorVan der Merwe, Nicoleen_ZA
dc.contributor.authorBouwens, Christianne S. H.en_ZA
dc.contributor.authorPienaar, Rikaen_ZA
dc.contributor.authorVan der Merwe, Lizeen_ZA
dc.contributor.authorYako, Yandiswa Y.en_ZA
dc.contributor.authorGeiger, Dieter H.en_ZA
dc.contributor.authorKotze, Maritha J.en_ZA
dc.date.accessioned2012-08-17T12:22:48Z
dc.date.available2012-08-17T12:22:48Z
dc.date.issued2012-05
dc.descriptionThe original article is available at http://link.springer.com/article/10.1007/s11011-012-9312-zen_ZA
dc.descriptionPublication of this article was funded by the Stellenbosch University Open Access Fund.en
dc.description.abstractApproximately 25 % of clinically important drugs and numerous environmental carcinogens are metabolised by CYP2D6. Variation in the CYP2D6 gene and concomitant use of tamoxifen (TAM) with certain antidepressants may increase recurrence risk in breast cancer patients due to reduced enzyme activity. In this study we determined the appropriateness of adding CYP2D6 genotyping to the breast cancer genetic testing options already available in South Africa, which include BRCA mutation screening and transcriptional profiling to assess estrogen receptor (ER) status. A total of 114 South African breast cancer patients, including 52 Caucasian and 62 Coloured (Mixed ancestry), and 63 Caucasian control individuals were genotyped for the most common inactivating allele (CYP2D6*4, rs3892097) previously identified in the CYP2D6 gene. In the initial validation data set consisting of 25 Caucasian and 62 Coloured patients, the CYP2D6*4 allele frequency was significantly higher in Caucasian compared to Coloured patients (24 % vs. 3 %, p≤0.001), similar to previous findings in the general South African population. Extended CYP2D6 genotyping was subsequently performed in an implementation data set of 27 Caucasian breast cancer patients, to determine the prevalence of depression and use of antidepressants in a clinical setting. A medical history of depression and/or use of antidepressants was reported in 37 % (10/27) of these breast cancer patients genotyped for CYP2D6*4. This translational research study has led to increased awareness among clinicians of the potential benefits of CYP2D6 genotyping to facilitate prevention of cumulative risk in a high-risk genetic subgroup of breast cancer patients considered for concomitant treatment of TAM and antidepressants that may reduce enzyme function. © Springer Science+Business Media, LLC 2012.en_ZA
dc.description.sponsorshipCancer Association of South Africa (CANSA),
dc.description.sponsorshipHarry Crossley Foundation and the National Research Foundationen_ZA
dc.format.extentpp. 319-326
dc.identifier.citationVan Der Merw, N. et al. 2012. CYP2D6 genotyping and use of antidepressants in breast cancer patients : test development for clinical application. Metabolic Brain Disease, 27(3):319-326, doi:10.1007/s11011-012-9312-z.en_ZA
dc.identifier.issn1573-7365 (online)
dc.identifier.issn0885-7490 (Print)
dc.identifier.otherdoi:10.1007/s11011-012-9312-z
dc.identifier.otherdoi:10.1007/s11011-012-9312-z
dc.identifier.urihttp://hdl.handle.net/10019.1/49250
dc.publisherSpringer Verlagen_ZA
dc.rights.holderAuthors retain copyright
dc.subjectAntidepressants -- Treatmenten_ZA
dc.subjectBrca2en_ZA
dc.subjectBreast cancer -- Diagnosisen_ZA
dc.subjectCYP2D6en_ZA
dc.subjectPharmacogeneticsen_ZA
dc.subjectTamoxifen -- Treatmenten_ZA
dc.titleCYP2D6 genotyping and use of antidepressants in breast cancer patients : test development for clinical applicationen_ZA
dc.typeArticleen_ZA
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