Zhao Haishan, Wang Zhe, Wu Huizhe, Xiao Qinghuan, Yao Weifan, Wang Enhua, Liu Yong, Wei Minjie
Department of Pharmacology, School of Pharmacy, China Medical University, Shenbei District, Shenyang City, 110013, Liaoning Province, People's Republic of China,
Med Oncol. 2015 Jan;32(1):375. doi: 10.1007/s12032-014-0375-z. Epub 2014 Dec 7.
The genetic or abnormal activation of signal transducer and activator of transcription (STATs) family proteins play an important role with regard to disease progression in variety of human malignancies, yet no data are available for candidate gene and breast cancer (BC) risk. To address this, we investigate the correlation between STAT3, STAT5b polymorphisms and BC susceptibility, clinicopathological parameters, and clinical outcomes. A case-control study was carried out in 1,240 BC patients and 882 healthy controls using TaqMan assay and PCR-RFLP method. A significant decreased risk of BC was associated with STAT3 G allele and combined effect (validation alleles). Furthermore, patients after anthracycline-based chemotherapy, carrying combined effect of STAT3 rs4796793 and STAT5b rs6503691, had significantly increased progression-free survival (PFS) [adjusted HR (95 % CI) 0.831 (0.704-0.980), P = 0.028]. More importantly, ER-negative patients with STAT5b CT/TT genotype was associated with a longer PFS [adjusted HR (95 % CI) 0.519 (0.293-0.920), P = 0.025], recurrence-free survival [adjusted HR (95 % CI) 0.529 (0.298-0.939), P = 0.030], and overall survival [adjusted HR (95 % CI) 0.547 (0.308-0.973), P = 0.040]. These results indicated that STAT3 and STAT5b polymorphisms might be a candidate pharmacogenomic factor to assess susceptibility and prognosis in BC patients.
信号转导子和转录激活子（STATs）家族蛋白的基因激活或异常激活在多种人类恶性肿瘤的疾病进展中起着重要作用，但关于候选基因与乳腺癌（BC）风险的数据尚不可得。为了解决这一问题，我们研究了STAT3、STAT5b基因多态性与BC易感性、临床病理参数及临床结局之间的相关性。采用TaqMan检测法和PCR-RFLP方法对1240例BC患者和882例健康对照进行了病例对照研究。BC风险显著降低与STAT3 G等位基因及联合效应（验证等位基因）相关。此外，接受蒽环类化疗的患者，携带STAT3 rs4796793和STAT5b rs6503691的联合效应，无进展生存期（PFS）显著延长[校正风险比（95%可信区间）0.831（0.704 - 0.980），P = 0.028]。更重要的是，STAT5b CT/TT基因型的雌激素受体阴性患者的PFS[校正风险比（95%可信区间）0.519（0.293 - 0.920），P = 0.025]、无复发生存期[校正风险比（95%可信区间）0.529（0.298 - 0.939），P = 0.030]和总生存期[校正风险比（95%可信区间）0.547（0.308 - 0.973），P = 0.040]均较长。这些结果表明，STAT3和STAT5b基因多态性可能是评估BC患者易感性和预后的候选药物基因组学因素。
