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

ABSTRACT: Approximately 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.

SUBMITTER: van der Merwe N

PROVIDER: S-EPMC3505529 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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

van der Merwe Nicole N Bouwens Christianne S H CS Pienaar Rika R van der Merwe Lize L Yako Yandiswa Y YY Geiger Dieter H DH Kotze Maritha J MJ

Metabolic brain disease 20120526 3

Approximately 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 tran ...[more]

PMID: 22638694

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Project description:The aim of the present study was to investigate the susceptibility of two coronary artery disease (CAD)-associated single nucleotide polymorphisms on 9p21 (rs1333049 and rs10757278) to myocardial infarction (MI) in a primary (stratification of high risk group for MI) and secondary prevention setting. The prospective observational study included 500 patients with MI [411 males (82.2%) and 89 females (17.8%)] under 65 years. The risk of MI for carriers of the homozygous CC genotype of rs1333049 and homozygous GG genotype of rs10757278 was 1.77 [95% confidence interval (CI): 1.36-2.37], and 1.70 (95% CI: 1.24-2.32) respectively. The risk of MI for heterozygous allele carriers was slightly lower. Specifically, the risk of MI was 1.58 (95% CI: 1.18-2.11) for both heterozygous and homozygous carriers of the rs1333049 C allele, and 1.36 (95% CI: 1.01-1.83) for the carriers of the rs10757278 G allele. A logistic regression model including sex, age, presence of excess weight or obesity, abdominal obesity, diabetes mellitus, arterial hypertension, hypercholesterolemia, positive family history and smoking status parameters revealed that rs1333049 CC genotype was an independent predictive factor of myocardial infraction [OR=1.71 (95% CI: 1.16-2.52), P=0.006]. Patients who underwent percutaneous coronary intervention (PCI) during index hospitalization and patients who did not receive PCI were followed up for two years after discharge. Compared with patients with MI who underwent PCI, the risk of recurrent acute coronary syndrome (re-ACS) was higher among rs1333049 C allele carriers who did not receive PCI during index hospitalization. One year after MI, the OR of re-ACS was 4.91 (95% CI: 1.45-16.66), while two years after MI, OR was 3.77 (95% CI: 1.50-9.52) in those patients who did not receive PCI during index hospitalization. There was no statistically significant association between polymorphic variants of rs1333049 and MI follow-up outcomes in patients who underwent PCI. The present study indicated clinical utility of 9p21.3 genotyping to predict the outcomes for patients with MI without PCI. Due to the small sample size, this association study forms basis for larger, nationwide studies investigating clinical applications of genetic data.

Dataset Information

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

Publications

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

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