CYP19 genetic polymorphism haplotype aasa is associated with a poor prognosis in premenopausal women with lymph node-negative, hormone receptor-positive breast cancer
Journal
BioMed Research International
Journal Volume
2013
Pages
562197
Date Issued
2013
Author(s)
Abstract
Given the critical role of CYP19 in estrogen synthesis, we investigated the influence of CYP19 gene polymorphisms on the clinical outcome of lymph node- (LN-) negative, hormone receptor- (HR-) positive early breast cancers. Genotyping for the CYP19 polymorphisms rs4646 (A/C), rs1065779 (A/C), CYP19 (TTTA)n (short allele/long (S/L) allele using the 7 TTTA repeat polymorphism as the cut-off), and rs1870050 (A/C) was performed on 296 patients with LN-negative, HR-positive breast cancers. All patients received adjuvant hormonal therapy. Associations were examined between these 4 genotypes and 6 common haplotypes of CYP19 and distant disease-free survival (DDFS), disease-free survival (DFS), and overall survival (OS). Patients were divided into the 6 subhaplotypes of CCLA (41.1%), AASA (17.1%), CASA (11.9%), CCLC (8.9%), CCSA (7.5%), AASC (8.9%), and others (4.6%). In premenopausal patients, haplotype AASA was significantly associated with a poor DDFS (adjusted hazard ratio (aHR), 3.3; P = 0.001), DFS (aHR, 2.5; P = 0.0008), and OS (aHR, 2.9; P = 0.0004) after adjusting for age, tumor size, tumor grade, estrogen receptor status, progesterone receptor status, chemotherapy, pathology, adjuvant hormone therapy, menopausal status, and radiotherapy. Furthermore, haplotype AASA remained a negative prognostic factor for premenopausal patients receiving adjuvant chemotherapy in terms of DDFS (aHR, 4.5; P = 0.0005), DFS (HR, 3.2; P = 0.003), and OS (HR, 6.4; P = 0.0009). However, in postmenopausal patients, haplotype AASA was not associated with a poor prognosis, whereas the AASC haplotype was significantly associated with a poor DFS (aHR, 3.1; P = 0.03) and OS (aHR, 4.4; P = 0.01). Our results indicate that, in patients with LN-negative, HR-positive breast cancers, genetic polymorphism haplotype AASA is associated with poor survival of premenopausal women but does not affect survival of postmenopausal women. ? 2013 Sung-Hsin Kuo et al.
Other Subjects
aromatase; estrogen receptor; progesterone receptor; aromatase; estrogen; estrogen receptor; adult; aged; article; breast cancer; cancer hormone therapy; cancer prognosis; cancer size; cancer survival; cohort analysis; disease free survival; DNA isolation; electrophoresis; female; genetic polymorphism; genotype; haplotype; hormone receptor positive breast cancer; human; human cell; human tissue; major clinical study; overall survival; polymerase chain reaction; postmenopause; premenopause; single nucleotide polymorphism; biosynthesis; breast tumor; genetics; haplotype; lymph node; middle aged; neoplasm; pathology; premenopause; prognosis; very elderly; Adult; Aged; Aged, 80 and over; Aromatase; Breast Neoplasms; Disease-Free Survival; Estrogens; Female; Haplotypes; Humans; Lymph Nodes; Middle Aged; Neoplasms, Hormone-Dependent; Polymorphism, Single Nucleotide; Premenopause; Prognosis; Receptors, Estrogen
Type
journal article