A Polymorphism at the 3′-UTR Region of the Aromatase Gene Is Associated with the Efficacy of the Aromatase Inhibitor, Anastrozole, in Metastatic Breast Carcinoma

Autor: Xiu Wei Sun, Rui Xie, Peng Huang, Xiao Li Wei, Qing Yuan Zhang, Yu Xian Bai, Ting-Ting Zhang, Wenjie Zhang, Yan Jing Li, Lei Liu, Jianhua Zhou, Heng Heng Yuan, Hong Sui, Jing Xuan Wang, Shu Zhao
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Oncology
Candidate gene
17-Hydroxysteroid Dehydrogenases
polymorphism
aromatase gene
Gene Frequency
Genotype
Aromatase
3' Untranslated Regions
Spectroscopy
Aged
80 and over
Aromatase Inhibitors
General Medicine
Middle Aged
Computer Science Applications
Female
medicine.drug
Adult
medicine.medical_specialty
medicine.drug_class
anastrozole
Anastrozole
Alpha-Ketoglutarate-Dependent Dioxygenase FTO
Breast Neoplasms
Biology
metastatic breast carcinoma
prognosis
Polymorphism
Single Nucleotide
Catalysis
Article
Inorganic Chemistry
Breast cancer
Internal medicine
Nitriles
medicine
Humans
Physical and Theoretical Chemistry
Allele
Molecular Biology
Allele frequency
Alleles
Aged
Retrospective Studies
Aromatase inhibitor
Organic Chemistry
Proteins
Triazoles
medicine.disease
Survival Analysis
Endocrinology
biology.protein
Zdroj: International Journal of Molecular Sciences
International Journal of Molecular Sciences; Volume 14; Issue 9; Pages: 18973-18988
ISSN: 1422-0067
Popis: Estrogen-related genes and the fat mass and obesity-associated (FTO) gene play a critical role in estrogen metabolism, and those polymorphisms are associated with a poor prognosis in breast cancer. However, little is known about the association between these polymorphisms and the efficacy of anastrozole. The aim was to investigate the impact of the genetic polymorphisms, CYP19A1, 17-β-HSD-1 and FTO, on the response to anastrozole in metastatic breast carcinoma (MBC) and to evaluate the impact of those polymorphisms on various clinicopathologic features. Two-hundred seventy-two women with hormone receptor-positive MBC treated with anastrozole were identified retrospectively. DNA was extracted from peripheral blood and genotyped for five variants in three candidate genes. Time to progression was improved in patients carrying the variant alleles of rs4646 when compared to patients with the wild-type allele (16.40 months versus 13.52 months; p = 0.049). The rs4646 variant alleles were significantly associated with longer overall survival (37.3 months versus 31.6 months; p = 0.007). This relationship was not observed with the rs10046, rs2830, rs9926298 and rs9939609 polymorphisms. The findings of this study indicate that rs4646 polymorphism in the CYP19A1 gene may serve as a prognostic maker of the response to anastrozole in patients with MBC who are treated with anastrozole.
Databáze: OpenAIRE
Externí odkaz: