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Impact of CYP2D6 Polymorphisms on Tamoxifen Responses of Women with Breast Cancer: A Microarray-based Study in Thailand

  • Sukasem, Chonlaphat (Division of Pharmacogenomics and Personalized Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University) ;
  • Sirachainan, Ekaphop (Division of Medical Oncology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University) ;
  • Chamnanphon, Montri (Division of Pharmacogenomics and Personalized Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University) ;
  • Pechatanan, Khunthong (Division of Medical Oncology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University) ;
  • Sirisinha, Thitiya (Division of Medical Oncology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University) ;
  • Ativitavas, Touch (Division of Medical Oncology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University) ;
  • Panvichian, Ravat (Division of Medical Oncology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University) ;
  • Ratanatharathorn, Vorachai (Division of Medical Oncology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University) ;
  • Trachu, Narumol (Research Center, Faculty of Medicine Ramathibodi Hospital, Mahidol University) ;
  • Chantratita, Wasun (Division of Virology, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University)
  • Published : 2012.09.30

Abstract

This study was designed to investigate the frequency of CYP2D6 polymorphisms and evaluate the association between genetic polymorphisms of CYP2D6 and tamoxifen therapeutic outcome in Thai breast cancer patients. We recruited 48 breast cancer patients who received adjuvant tamoxifen for evaluating CYP2D6 genetic polymorphisms using microarray-based technology. Associations between genotypes-phenotypes and disease free survival were analyzed. Median follow up time was 5.6 years. The mean age of the subjects was 50 years. The 3 common allelic frequencies were 43.8% ($^*10$), 36.5 ($^*1$) and 10.4% ($^*2$) which are related to extensive metabolizer (EM) and intermediate metabolizer (IM) with 70.8% and 29.2 %, respectively. No association between CYP2D6 genotypes and DFS was demonstrated. Nevertheless, exploratory analysis showed statistically significant shorter DFS in the IM group of post-menopause patients (HR, 6.85; 95%CI, 1.48-31.69; P=0.005). Furthermore, we observed statistically significant shorter DFS of homozygous $CYP2D6^*10$ when compared with heterozygous CYP2D6*10 and other genotypes (P=0.005). $CYP2D6^*10$ was the most common genotype in our subjects. Post-menopause patients with homozygous $CYP2D6^*10$ and IM have shorter DFS. To confirm this relationship, larger samples and comprehensively designed trials in Thailand are required.

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