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21 February 2015 : Clinical Research  

Association of CYP2D6*10, OATP1B1 A388G, and OATP1B1 T521C Polymorphisms and Overall Survival of Breast Cancer Patients after Tamoxifen Therapy

Xuefeng ZhangABCEF, Zhichen PuBDE, Jun GeCDF, Jie ShenCD, Xiaolong YuanBD, Haitang XieADG

DOI: 10.12659/MSM.893473

Med Sci Monit 2015; 21:563-569

Abstract

BACKGROUND: The global incidence of breast cancer is increasing, mainly due to the sharp rise in breast cancer incidence in Asia. The aim of this study was to evaluate the association of CYP2D6*10 (c.100C>T and c.1039C>T), OATP1B1 A388G, and OATP1B1 T521C polymorphisms with overall survival (OS) for hormone receptor (estrogen receptor or progesterone receptor)-positive tumors (ER+/PR+) breast cancer patients after adjuvant tamoxifen (TAM) therapy.

MATERIAL AND METHODS: We included 296 invasive breast cancer patients with hormone receptor-positive tumors during the period 2002–2009. We collected patient data, including clinical features, TAM therapy, and survival status. Archived paraffin blocks from surgery were the source of tissue for genotyping. CYP2D6*10, OATP1B1 A388G, and T521C polymorphisms were detected by direct sequencing of genomic DNA. OS was assessed with Kaplan-Meier analysis, while the Cox proportional hazards model was used to implement multivariate tests for the prognostic significance.

RESULTS: There was a significant difference in OS between OATP1B1 T521C wild-type and the mutant genotype C carrier (P=0.034). However, there was no difference in overall survival between wild-type and carrier groups for CYP2D6*10 (P=0.096) and OATP1B1 A388G (P=0.388), respectively.

CONCLUSIONS: These results suggest that the OATP1B1 T521C mutation may be an independent prognostic marker for breast cancer patients using TAM therapy.

Keywords: Aged, 80 and over, Breast Neoplasms - genetics, Cytochrome P-450 CYP2D6 - genetics, Gene Frequency - genetics, Genetic Association Studies, Genetic Predisposition to Disease, Kaplan-Meier Estimate, Organic Anion Transporters - genetics, Polymorphism, Single Nucleotide - genetics, Proportional Hazards Models, Tamoxifen - therapeutic use

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750