title: AQP5 Variants Affect Tumoral Expression of AQP5 and Survival in Patients with Early Breast Cancer.
abstract: BACKGROUND
  Our previous study showed the association of AQP5 upregulation with cancer proliferation and migration in breast cancer cell lines and with unfavorable prognosis in patients with early breast cancer (EBC). In the current study, we analyzed the association of AQP5 variants or their haplotypes with AQP5 expression and their prognostic impact for survival in patients with EBC.
  
  
  METHODS
  Three AQP5 polymorphisms (rs74091166, rs3736309, and rs1964676) were selected based on the SNP database and genotyped using the Sequenom MassARRAY in 374 out of 447 patients with EBC in whom AQP5 expression had been investigated in our previous study.
  
  
  RESULTS
  The allele frequencies of the selected variants in the current study were similar to those from Asian data previously reported. In a univariate analysis, both rs74091166 and rs1964676 were statistically associated with survival as a dominant model of minor allele. Moreover, a multivariate survival analysis revealed that the CC genotype of rs1964676 is an independent prognostic marker of survival in EBC patients, regardless of stage, tumor subtype, and adjuvant treatment [hazard ratio = 0.399, 0.384, and 0.205; p = 0.021, 0.027, and 0.016 for disease-free survival (DFS), distant DFS, and disease-specific survival, respectively]. In particular, the CT/TT genotype of rs1964676 showed an association with strong expression of AQP5 (58.6 vs. 26.0%; p = 0.001), without any associations with clinical or pathological characteristics including tumor subtype, stage, or histologic grade.
  
  
  CONCLUSIONS
  The current study suggests AQP5 rs1964676 as a new potential prognostic marker in patients with EBC involved in AQP5 expression.
authors.affiliation: Department of Oncology/Hematology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: Soo Jung
authors.initials: SJ
authors.lastname: Lee
authors.forename: Byung Woog
authors.initials: BW
authors.lastname: Kang
authors.forename: Jong Gwang
authors.initials: JG
authors.lastname: Kim
authors.forename: Jin Hyang
authors.initials: JH
authors.lastname: Jung
authors.forename: Jeeyeon
authors.initials: J
authors.lastname: Lee
authors.forename: Wan Wook
authors.initials: WW
authors.lastname: Kim
authors.forename: Ho Yong
authors.initials: HY
authors.lastname: Park
authors.forename: Jae-Hwan
authors.initials: JH
authors.lastname: Jeong
authors.forename: Ji Yun
authors.initials: JY
authors.lastname: Jeong
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Park
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Park
authors.forename: Yee Soo
authors.initials: YS
authors.lastname: Chae
mesh_terms: D000328:Adult; D000368:Aged; D051402:Aquaporin 5 / Q000096:biosynthesis* / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis
chemical_list: C496036:AQP5 protein, human; D051402:Aquaporin 5