title: STAT3 genetic variant, alone and in combination with STAT5b polymorphism, contributes to breast cancer risk and clinical outcomes.
abstract: 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.
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, Shenbei District, Shenyang City, 110013, Liaoning Province, People's Republic of China, haishan_zhao@126.com.
authors.forename: Haishan
authors.initials: H
authors.lastname: Zhao
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.forename: Huizhe
authors.initials: H
authors.lastname: Wu
authors.forename: Qinghuan
authors.initials: Q
authors.lastname: Xiao
authors.forename: Weifan
authors.initials: W
authors.lastname: Yao
authors.forename: Enhua
authors.initials: E
authors.lastname: Wang
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.forename: Minjie
authors.initials: M
authors.lastname: Wei
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality; D016022:Case-Control Studies; D018572:Disease-Free Survival; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D050796:STAT3 Transcription Factor / Q000235:genetics*; D050799:STAT5 Transcription Factor / Q000235:genetics*; D055815:Young Adult
chemical_list: D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; C494095:STAT5B protein, human