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.

Abstract

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.

• Authors: Lei Liu, Yu-Xian Bai, Jian-Hua Zhou, Xiu-Wei Sun, Hong Sui, Wen-Jie Zhang, Heng-Heng Yuan, Rui Xie, Xiao-Li Wei, Ting-Ting Zhang, Peng Huang, Yan-Jing Li, Jing-Xuan Wang, Shu Zhao, Qing-Yuan Zhang
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 14 Issue 9 Pg. 18973-88 (Sep 13 2013) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 24065098 (Publication Type: Journal Article)

Chemical References

• 3' Untranslated Regions
• Aromatase Inhibitors
• Nitriles
• Proteins
• Triazoles
• Anastrozole
• 17-Hydroxysteroid Dehydrogenases
• Alpha-Ketoglutarate-Dependent Dioxygenase FTO
• FTO protein, human
• Aromatase

Topics

• 17-Hydroxysteroid Dehydrogenases (genetics)
• 3' Untranslated Regions
• Adult
• Aged
• Aged, 80 and over
• Alleles
• Alpha-Ketoglutarate-Dependent Dioxygenase FTO
• Anastrozole
• Aromatase (genetics)
• Aromatase Inhibitors (therapeutic use)
• Breast Neoplasms (drug therapy, genetics, pathology)
• Female
• Gene Frequency
• Genotype
• Humans
• Middle Aged
• Nitriles (therapeutic use)
• Polymorphism, Single Nucleotide
• Proteins (genetics)
• Retrospective Studies
• Survival Analysis
• Triazoles (therapeutic use)