title: Association of CTLA4 and CD28 Gene Variants and Circulating Levels of Their Proteins in Patients with Breast Cancer.
abstract: OBJECTIVE
  Breast cancer is one of the most common and lethal types of cancer among women. We focused on the importance of the immune system in the etiology of breast cancer by investigating critical polymorphisms of cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and cluster of differentiation 28 (CD28) gene, and circulating levels of these proteins.
  
  
  METHODS
  A total of 79 patients with breast cancer and 76 healthy controls were enrolled. Molecular assessment of CTLA4 (rs231775&rs5742909) and CD28 (rs3116496) variants were determined with polymerase chain reaction restriction fragment length polymorphism techniques. Circulating levels of soluble forms of CTLA4 and CD28 were analyzed by ELISA.
  
  
  RESULTS
  Although no significant association was found between study groups, CTLA4 +49AA genotypic frequency, and sCTLA4 and sCD28 levels were higher in patients. Some clinicopathological features were also related with CTLA4 and CD28 variants and blood levels.
  
  
  CONCLUSIONS
  While CTLA4 +49AA genotype is increased in patients with breast cancer, the CTLA4 -318T allele may have a prognostic value. In addition, sCTLA4 and sCD28 can be used for diagnostic purposes in patients with breast cancer.
authors.affiliation: Immunology Laboratory, Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey.
authors.forename: Gulbu
authors.initials: G
authors.lastname: Isitmangil
authors.affiliation: General Surgery Clinics, Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey.
authors.forename: Gunay
authors.initials: G
authors.lastname: Gurleyik
authors.affiliation: Pathology Laboratory, Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey.
authors.forename: Fugen Vardar
authors.initials: FV
authors.lastname: Aker
authors.affiliation: Department of Biochemistry, Haseki Training and Research Hospital, Istanbul, Turkey.
authors.forename: Cihan
authors.initials: C
authors.lastname: Coskun
authors.affiliation: Department of Molecular Medicine, Institute of Experimental Medicine, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Kucukhuseyin
authors.affiliation: General Surgery Clinics, Istanbul Educating and Training Hospital, Istanbul, Turkey.
authors.forename: Soykan
authors.initials: S
authors.lastname: Arikan
authors.affiliation: Department of Molecular Medicine, Institute of Experimental Medicine, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Saime
authors.initials: S
authors.lastname: Turan
authors.affiliation: Pathology Laboratory, Istanbul Educating and Training Hospital, Istanbul, Turkey.
authors.forename: Canan Kelten
authors.initials: CK
authors.lastname: Talu
authors.affiliation: General Surgery Clinics, Istanbul Educating and Training Hospital, Istanbul, Turkey.
authors.forename: Mehmet Baki
authors.initials: MB
authors.lastname: Dogan
authors.affiliation: Laboratory for Translational Oncology and Personalized Medicine, Rashid Latif Medical College, Lahore, Pakistan.
authors.forename: Ammad Ahmad
authors.initials: AA
authors.lastname: Farooqi
authors.affiliation: Department of Molecular Medicine, Institute of Experimental Medicine, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey ilhanyaylim@gmail.com.
authors.forename: Ilhan
authors.initials: I
authors.lastname: Yaylim
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D001943:Breast Neoplasms / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D018106:CD28 Antigens / Q000097:blood / Q000235:genetics*; D060908:CTLA-4 Antigen / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human
keywords: Breast cancer; CD28; CTLA4 +49 A>G; CTLA4 -318 C>T