Genetic polymorphism of <i>CYP2D6</i>
 in Chinese subjects in Malaysia

Ismail, Rusli; Teh, Lay Kek; Amir, J.; Alwi, Zilfalil; Lopez, C G

doi:10.1046/j.1365-2710.2003.00490.x

Cited by 22 publications

(25 citation statements)

References 27 publications

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“…In our previous study in 52 Malay male subjects given a single 8 mg dose of methadone, we found a wide variability in its clearance, consistent with other studies previously reported [28]. The variability in our 52 subjects could not be explained by polymorphisms at the CYP2D6 locus, a very polymorphic gene in our population [19][20][21], another enzyme implicated in methadone metabolism [29]. This led us to investigate the genetic polymorphism at the CYP3A4 locus among heroin drug users.…”

Section: Discussionsupporting

confidence: 89%

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High Frequency of CYP3A4*1B among Opiate Dependent Patients in Malaysia

M¹,

A²

2012

J Addict Res Ther

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Section: Discussionsupporting

confidence: 89%

“…Malaysia is a multiethnic country where genetic polymorphisms of several drug metabolizing enzymes have been previously described [19][20][21][22][23][24][25][26]. Although our earlier studies failed to detect polymorphism at the CY3A4 locus, mutant alleles have recently been described in Malaysia [27].…”

Section: Introductionmentioning

confidence: 98%

High Frequency of CYP3A4*1B among Opiate Dependent Patients in Malaysia

M¹,

A²

2012

J Addict Res Ther

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“…The frequency of this allele is approximately 37% to 70%, 50%, and 40%, respectively, in Chinese (21,22), Koreans (23,24), and Japanese (25,26) compared with only 2% in European Caucasians (11). Two early Southeast Asian studies reported the CYP2D6*1/CYP2D6*10 to be the most common genotype in Malays and Chinese in Malaysia (27,28). A Korean study in metastatic breast cancer patients found that CYP2D6*10 homozygotes had lower plasma levels of tamoxifen metabolites and a correspondingly shorter time to progression (TTP) compared with other CYP2D6 genotypes (13).…”

Section: Genes/polymorphismsmentioning

confidence: 99%

Pharmacogenetics in Breast Cancer Therapy

Tan

Lee

Goh

et al. 2008

Clinical Cancer Research

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Interindividual and interethnic variability of drug pharmacokinetics and pharmacodynamics may be contributed by commonly occurring genetic polymorphisms of drug-metabolizing enzymes and transporters. Polymorphisms of CYP2D6 in particular have been associated with effects on tamoxifen disposition and clinical efficacy, with interethnic differences in distribution of functional alleles that affect metabolizer phenotype. Other tamoxifen-related genetic variants of CYP3A4, CYP3A5, and sulfotransferase1A1 (SULT1A1) are also briefly reviewed here. Polymorphisms of CYP19A1 (aromatase gene) have been reported to correlate with clinical outcomes from aromatase inhibitors in small studies but require further confirmation. Many studies on chemotherapy are based on hypothesis-generating association studies and need to be validated through larger-scale cooperative group studies. For anthracyclines, polymorphisms in genes such as carbonyl reductase 3 (CBR3), ATP-binding cassette subfamily B, member 1 (ABCB1), glutathione-related transporter genes, and oxidative stress^related genes have been reported to correlate with clinical outcomes. The pharmacogenetics of taxanes has been extensively investigated, but associations of genetic polymorphisms in drug-metabolizing enzymes and transporters reported in earlier small studies have not been validated in a recent large clinical trial. Allelic variants associated with gemcitabine, capecitabine/5-fluorouracil, vinorelbine, and platinum disposition are reviewed. No pharmacogenetic studies have been published for targeted agents thus far, although several potential candidate genes warrant investigation. Future pharmacogenetic studies will need to focus on integration of multiple drug pathways to allow a more comprehensive analysis of genetic factors influencing drug efficacy and toxicity.

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“…Our earlier studies reported the heterogeneity of CYP2D6 among the three different ethnic groups in Malaysia (23)(24)(25)(26), but no studies have investigated the influence of the polymorphism of CYP2D6 and ABCB1 in tamoxifen therapy among the patients in Malaysia. We therefore investigated the impact of CYP2D6 and ABCB1 genotypes on the outcomes of tamoxifen therapy in a cohort of breast cancer patients.…”

Section: Introductionmentioning

confidence: 99%

The Risk of Recurrence in Breast Cancer Patients Treated with Tamoxifen: Polymorphisms of CYP2D6 and ABCB1

Teh

Mohamed

Salleh

et al. 2011

AAPS J

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Abstract. CYP2D6 plays a major role in the metabolism of tamoxifen, and polymorphism of Pglycoprotein has been associated with resistance of many drug therapies. This study investigates the clinical impact of genetic variants of CYP2D6 and ABCB1 in breast cancer patients treated with tamoxifen. Blood samples from 95 breast cancer patients treated with tamoxifen were collected and genotyped for CYP2D6 and ABCB1 variants using allele-specific PCR method. Recurrence risks were calculated using Kaplan-Meier analysis and compared using the log-rank test. Patients carrying CYP2D6*10/*10 and heterozygous null allele (IM) showed higher risks of developing recurrence and metastasis (OR 13.14; 95% CI 1.57-109.94; P=0.004) than patients with CYP2D6*1/*1 and *1/*10 genotypes. Patients with homozygous CC genotypes of ABCB1 C3435T showed a shorter time to recurrence. Patients who were CYP2D6 IM and homozygous CC genotype of C3435T have statistically significant higher risks of recurrence (P=0.002). Similarly, median time to recurrence in these patients was only 12 months (95% CI=0.79-23.2) compared to those without this combination which was 48 months (95% CI=14.7-81.2). Patients with CYP2D6 IM and homozygous CC genotype of ABCB1 C3435T have shorter times to recurrence. The results confirmed the findings of previous studies and support FDA recommendation to perform pre-genotyping in patients before the choice of therapy is determined in breast cancer patients.KEY WORDS: ABCB1; breast cancer; CYP2D6; recurrence and metastasis; tamoxifen.

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Genetic polymorphism of CYP2D6 in Chinese subjects in Malaysia

Cited by 22 publications

References 27 publications

High Frequency of CYP3A4*1B among Opiate Dependent Patients in Malaysia

High Frequency of CYP3A4*1B among Opiate Dependent Patients in Malaysia

Pharmacogenetics in Breast Cancer Therapy

The Risk of Recurrence in Breast Cancer Patients Treated with Tamoxifen: Polymorphisms of CYP2D6 and ABCB1

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