title: Comparison of telomere length and insulin-like growth factor-binding protein 7 promoter methylation between breast cancer tissues and adjacent normal tissues in Turkish women.
abstract: BACKGROUND
  Both insulin-like growth factor-binding protein 7 (IGFBP7) and telomere length (TL) are associated with proliferation and senescence of human breast cancer. This study assessed the clinical significance of both TL and IGFBP7 methylation status in breast cancer tissues compared with adjacent normal tissues. We also investigated whether IGFBP7 methylation status could be affecting TL.
  
  
  METHODS
  Telomere length was measured by quantitative PCR to compare tumors with their adjacent normal tissues. The IGFBP7 promoter methylation status was evaluated by methylation-specific PCR and its expression levels were determined by western blotting.
  
  
  RESULTS
  Telomeres were shorter in tumor tissues compared to controls (P<.0001). The mean TL was higher in breast cancer with invasive ductal carcinoma (IDC; n=72; P=.014) compared with other histological type (n=29), and TL in IDC with HER2 negative (n=53; P=.017) was higher than TL in IDC with HER2 positive (n=19). However, telomeres were shortened in advanced stages and growing tumors. IGFBP7 methylation was observed in 90% of tumor tissues and 59% of controls (P=.0002). Its frequency was significantly higher in IDC compared with invasive mixed carcinoma (IMC; P=.002) and it was not correlated either with protein expression or the other clinicopathological parameters.
  
  
  CONCLUSIONS
  These results suggest that IGFBP7 promoter methylation and shorter TL in tumor compared with adjacent tissues may be predictive biomarkers for breast cancer. Telomere maintenance may be indicative of IDC and IDC with HER2 (-) of breast cancer. Further studies with larger number of cases are necessary to verify this association.
authors: Medical Biology Department, School of Medicine, Marmara University, Istanbul, Turkey.|Medical Biology Department, School of Medicine, Yüzüncü Yıl University, Van, Turkey.
authors: Zehra
authors: http://orcid.org/0000-0001-6222-7882
authors: Z
authors: Kaya
authors: Medical Biology Department, School of Medicine, Marmara University, Istanbul, Turkey.
authors: Mustafa
authors: M
authors: Akkiprik
authors: Medical Biology Department, School of Medicine, Marmara University, Istanbul, Turkey.|Health Services Vocational School, Bayburt University, Bayburt, Turkey.
authors: Sevgi
authors: S
authors: Karabulut
authors: Medical Biology Department, School of Medicine, Marmara University, Istanbul, Turkey.
authors: Irem
authors: I
authors: Peker
authors: Medical Biology Department, School of Medicine, Marmara University, Istanbul, Turkey.
authors: Gokce
authors: G
authors: Gullu Amuran
authors: General Surgery, School of Medicine, Marmara University, Istanbul, Turkey.
authors: Tolga
authors: T
authors: Ozmen
authors: General Surgery, School of Medicine, Marmara University, Istanbul, Turkey.
authors: Bahadır M
authors: BM
authors: Gulluoglu
authors: Pathology Department, School of Medicine, Marmara University, Istanbul, Turkey.
authors: Handan
authors: H
authors: Kaya
authors: Medical Biology Department, School of Medicine, Marmara University, Istanbul, Turkey.
authors: Ayse
authors: A
authors: Ozer
mesh_terms: D001940:Breast / Q000737:chemistry*; D001943:Breast Neoplasms / Q000737:chemistry / Q000453:epidemiology* / Q000235:genetics* / Q000401:mortality; D015331:Cohort Studies; D019175:DNA Methylation; D005260:Female; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics*; D008875:Middle Aged; D016019:Survival Analysis; D016615:Telomere / Q000737:chemistry / Q000235:genetics*; D014421:Turkey
chemical_list: D018969:Insulin-Like Growth Factor Binding Proteins; C102529:insulin-like growth factor binding protein-related protein 1
keywords: breast cancer; insulin-like growth factor-binding protein 7; methylation; telomere; telomere length