Publication: Association of CYP3A4/5, ABCB1 and ABCC2 polymorphisms and clinical outcomes of Thai breast cancer patients treated with tamoxifen
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Issued Date
2013-08-23
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11787066
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2-s2.0-84883228374
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Mahidol University
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SCOPUS
Bibliographic Citation
Pharmacogenomics and Personalized Medicine. Vol.6, No.1 (2013), 93-98
Suggested Citation
Insee Sensorn, Ekaphop Sirachainan, Montri Chamnanphon, Ekawat Pasomsub, Narumol Trachu, Porntip Supavilai, Chonlaphat Sukasem, Darawan Pinthong Association of CYP3A4/5, ABCB1 and ABCC2 polymorphisms and clinical outcomes of Thai breast cancer patients treated with tamoxifen. Pharmacogenomics and Personalized Medicine. Vol.6, No.1 (2013), 93-98. doi:10.2147/PGPM.S44006 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/31239
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Title
Association of CYP3A4/5, ABCB1 and ABCC2 polymorphisms and clinical outcomes of Thai breast cancer patients treated with tamoxifen
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Abstract
Background: Pharmacogenetic study of cytochrome P450 (CYP) gene CYP2D6 and tamoxifen outcomes remain controversial. Apart from CYP2D6, other drug-metabolizing enzymes and transporters also play a role in tamoxifen metabolic pathways. The aim of this study is to investigate the impact of CYP3A4/5, ABCB1, and ABCC2 polymorphisms on the risk of recurrence in Thai patients who received tamoxifen adjuvant therapy. Methods: Patients with early-stage breast cancer who received tamoxifen adjuvant therapy were recruited in this study. All six single-nucleotide polymorphisms (SNPs), including CYP3A4*1B (-392 A>G)/*18(878 T>C), CYP3A5*3(6986 G>A), ABCB1 3435 C>T, ABCC2*1C (-24 C>T), and ABCC2 68231 A>G, were genotyped using real-time polymerase chain reaction assays. The impacts of genetic variants on disease-free survival (DFS) were analyzed using the Kaplan-Meier method and Cox regression analysis. Results: The ABCB1 3435 C>T was found to have the highest allele frequency among other variants; however, CYP3A4*1B/*18 could not be found in this study. Patients with heterozygous ABCB1 3435 CT genotype showed significantly shorter DFS than those with homozygous 3435 CC genotype (P = 0.041). In contrast, patients who carried homozygous 3435 TT genotype showed no difference in DFS from wild-type 3435 CC patients. Cox regression analysis showed that the relative risk of recurrence was increased by five times (P = 0.043; hazard ratio = 5.11; 95% confidence interval: 1.05-24.74) in those patients carrying ABCB1 3435 CT genotype compared to those with ABCB1 3435 CC. Conclusion: ABCB1 3435 C>T is likely to have a clinically significant impact on recurrence risk in Thai patients with breast cancer who receive tamoxifen adjuvant therapy. © 2013 Sensorn et al, publisher and licensee Dove Medical Press Ltd.