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.
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.
Department of Internal Medicine, The Affiliated Tumor Hospital, Harbin Medical University, Haping Road 150 of Nangang District, Harbin 150081, Heilongjiang, China. zhma19650210@yeah.net.
Lei
L
Liu
Yu-Xian
YX
Bai
Jian-Hua
JH
Zhou
Xiu-Wei
XW
Sun
Hong
H
Sui
Wen-Jie
WJ
Zhang
Heng-Heng
HH
Yuan
Rui
R
Xie
Xiao-Li
XL
Wei
Ting-Ting
TT
Zhang
Peng
P
Huang
Yan-Jing
YJ
Li
Jing-Xuan
JX
Wang
Shu
S
Zhao
Qing-Yuan
QY
Zhang
D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics; D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D000077384:Anastrozole; D001141:Aromatase / Q000235:genetics*; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009570:Nitriles / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics; D012189:Retrospective Studies; D016019:Survival Analysis; D014230:Triazoles / Q000627:therapeutic use*
D020413:3' Untranslated Regions; D047072:Aromatase Inhibitors; D009570:Nitriles; D011506:Proteins; D014230:Triazoles; D000077384:Anastrozole; D015067:17-Hydroxysteroid Dehydrogenases; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human; D001141:Aromatase