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BioMed Research International
Volume 2013 (2013), Article ID 562197, 9 pages
http://dx.doi.org/10.1155/2013/562197
Research Article

CYP19 Genetic Polymorphism Haplotype AASA Is Associated with a Poor Prognosis in Premenopausal Women with Lymph Node-Negative, Hormone Receptor-Positive Breast Cancer

1Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
2Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
3Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan
4Genomics Research Center, Academia Sinica, Taipei, Taiwan
5Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan
6Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
7Department of Surgery, National Taiwan University Hospital, No. 7, Chung-Shan South Rd, Taipei 100, Taiwan

Received 2 July 2013; Revised 23 September 2013; Accepted 24 September 2013

Academic Editor: Franco M. Buonaguro

Copyright © 2013 Sung-Hsin Kuo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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; ), DFS (aHR, 2.5; ), and OS (aHR, 2.9; ) 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; ), DFS (HR, 3.2; ), and OS (HR, 6.4; ). 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; ) and OS (aHR, 4.4; ). 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.