title: Genetic polymorphisms in APE1 Asp148Glu(rs3136820) as a modifier of the background levels of abasic sites in human leukocytes derived from breast cancer patients and controls.
abstract: BACKGROUND
  Apurinic/apyrimidinic (abasic/AP) sites are among the most common endogenous DNA lesions. AP sites, if not repaired, could result in genomic instability as well as chromosome aberrations. Information regarding the direct assay of the number of abasic sites in human leukocytes and its association with risk of breast cancer has not been reported.
  
  
  METHODS
  In this study, we investigated the association between certain risk factors for breast cancer and the background levels of AP sites in leukocytes derived from 148 Taiwanese women with breast cancer and 140 cancer-free controls. The risk factors studied include age, body mass index (BMI), and polymorphisms of apurinic/apyrimidinic endonuclease (APE1) [APE1 Asp148Glu(rs3136820)].
  
  
  RESULTS
  Mean levels of AP sites were estimated to be 23.3 and 50.3 per 106nucleotides in controls and breast cancer patients, respectively (~twofold, p < 0.001). In subjects with age <50 or BMI < 27 (kg/m2), the levels of AP sites in breast cancer patients were ~2-3-fold greater than those of controls (p < 0.05). Additionally, results from the AP site 3'-cleavage assay indicated that the AP sites detected in both controls and patients were likely to be oxidant-mediated 5'-cleaved AP sites (~61-64 %). The number of AP sites in breast cancer patients was ~twofold greater in subjects with Asp/Glu + Glu/Glugenotypes than those with Asp/Asp genotype (p < 0.001).
  
  
  CONCLUSIONS
  We confirmed that cumulative body burden of AP sites is a significant predictor of the risk of developing breast cancer and that genetic predisposition and environment factors may modulate the induction of oxidative DNA lesions in breast cancer patients.
authors.affiliation: Department of Laboratory Medicine, Da-Chien General Hospital, Miaoli, Taiwan.
authors.forename: Wei-Chung
authors.initials: WC
authors.lastname: Hsieh
authors.affiliation: Comprehensive Breast Cancer Center, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Che
authors.initials: C
authors.lastname: Lin
authors.affiliation: Comprehensive Breast Cancer Center, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Dar-Ren
authors.initials: DR
authors.lastname: Chen
authors.affiliation: Department of Laboratory Medicine, Da-Chien General Hospital, Miaoli, Taiwan.
authors.forename: Wen-Fa
authors.initials: WF
authors.lastname: Yu
authors.affiliation: Department of Environmental Engineering, National Chung Hsing University, Taichung, 402, Taiwan.
authors.forename: Guan-Jie
authors.initials: GJ
authors.lastname: Chen
authors.affiliation: College of Oral Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Suh-Woan
authors.initials: SW
authors.lastname: Hu
authors.affiliation: Department of Environmental Engineering, National Chung Hsing University, Taichung, 402, Taiwan.
authors.forename: Chin-Chen
authors.initials: CC
authors.lastname: Liu
authors.affiliation: Department of Environmental Engineering, National Chung Hsing University, Taichung, 402, Taiwan.
authors.forename: Mao-Huei
authors.initials: MH
authors.lastname: Ge
authors.affiliation: Department of Environmental Engineering, National Chung Hsing University, Taichung, 402, Taiwan.
authors.forename: Chang-Sin
authors.initials: CS
authors.lastname: Ruan
authors.affiliation: Department of Environmental Engineering, National Chung Hsing University, Taichung, 402, Taiwan.
authors.forename: Cheng-You
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Department of Biotechnology, National Formosa University, Yunlin, 63208, Taiwan.
authors.forename: Chia-Hua
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Department of Environmental Engineering, National Chung Hsing University, Taichung, 402, Taiwan. pohsiunglin@yahoo.com.
authors.forename: Po-Hsiung
authors.initials: PH
authors.lastname: Lin
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D016022:Case-Control Studies; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007962:Leukocytes / Q000473:pathology*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011700:Putrescine / Q000378:metabolism
chemical_list: D004247:DNA; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D011700:Putrescine
keywords: AP sites; Biomarker; DNA repair; Oxidative stress