Kuo Sung-Hsin, Yang Shi-Yi, Lien Huang-Chun, Lo Chiao, Lin Ching-Hung, Lu Yen-Sen, Cheng Ann-Lii, Chang King-Jeng, Huang Chiun-Sheng
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.
Biomed Res Int. 2013;2013:562197. doi: 10.1155/2013/562197. Epub 2013 Nov 14.
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.
鉴于细胞色素P450 19（CYP19）在雌激素合成中的关键作用，我们研究了CYP19基因多态性对淋巴结（LN）阴性、激素受体（HR）阳性早期乳腺癌临床结局的影响。对296例LN阴性、HR阳性乳腺癌患者进行了CYP19多态性rs4646（A/C）、rs1065779（A/C）、CYP19（TTTA）n（以7个TTTA重复多态性为界分为短等位基因/长（S/L）等位基因）和rs1870050（A/C）的基因分型。所有患者均接受辅助激素治疗。研究了这4种基因型和CYP19的6种常见单倍型与远处无病生存期（DDFS）、无病生存期（DFS）和总生存期（OS）之间的关联。患者被分为CCLA（41.1%）、AASA（17.1%）、CASA（11.9%）、CCLC（8.9%）、CCSA（7.5%）、AASC（8.9%）和其他（4.6%）6种单倍型。在绝经前患者中，调整年龄、肿瘤大小、肿瘤分级、雌激素受体状态、孕激素受体状态、化疗、病理、辅助激素治疗、绝经状态和放疗后，单倍型AASA与较差的DDFS（调整后风险比（aHR），3.3；P = 0.001）、DFS（aHR，2.5；P = 0.0008）和OS（aHR，2.9；P = 0.0004）显著相关。此外，就DDFS（aHR，4.5；P = 0.0005）、DFS（HR，3.2；P = 0.003）和OS（HR，6.4；P = 0.0009）而言，单倍型AASA仍然是接受辅助化疗的绝经前患者的不良预后因素。然而，在绝经后患者中，单倍型AASA与不良预后无关，而单倍型AASC与较差的DDFS（aHR，3.1；P = 0.03）和OS（aHR，4.4；P = 0.01）显著相关。我们的结果表明，在LN阴性、HR阳性乳腺癌患者中，基因多态性单倍型AASA与绝经前女性的不良生存相关，但不影响绝经后女性的生存。
