title: CYP19 genetic polymorphism haplotype AASA is associated with a poor prognosis in premenopausal women with lymph node-negative, hormone receptor-positive breast cancer.
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.
authors: Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan ; Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan ; Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Sung-Hsin
authors: SH
authors: Kuo
authors: Shi-Yi
authors: SY
authors: Yang
authors: Huang-Chun
authors: HC
authors: Lien
authors: Chiao
authors: C
authors: Lo
authors: Ching-Hung
authors: CH
authors: Lin
authors: Yen-Sen
authors: YS
authors: Lu
authors: Ann-Lii
authors: AL
authors: Cheng
authors: King-Jeng
authors: KJ
authors: Chang
authors: Chiun-Sheng
authors: CS
authors: Huang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001141:Aromatase / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D004967:Estrogens / Q000096:biosynthesis; D005260:Female; D006239:Haplotypes; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D017697:Premenopause; D011379:Prognosis; D011960:Receptors, Estrogen / Q000235:genetics
chemical_list: D004967:Estrogens; D011960:Receptors, Estrogen; D001141:Aromatase