title: Cigarette smoking and hOGG1 Ser326Cys polymorphism are associated with 8-OHdG accumulation on mitochondrial DNA in thoracic esophageal squamous cell carcinoma.
abstract: BACKGROUND
  We examined whether cigarette smoking affects the degrees of oxidative damage (8-hydroxyl-2'-deoxyguanosine [8-OHdG]) on mitochondrial DNA (mtDNA), whether the degree of 8-OHdG accumulation on mtDNA is related to the increased total mtDNA copy number, and whether human 8-oxoguanine DNA glycosylase 1 (hOGG1) Ser326Cys polymorphisms affect the degrees of 8-OHdG accumulation on mtDNA in thoracic esophageal squamous cell carcinoma (TESCC).
  
  
  METHODS
  DNA extracted from microdissected tissues of paired noncancerous esophageal muscles, noncancerous esophageal mucosa, and cancerous TESCC nests (n = 74) along with metastatic lymph nodes (n = 38) of 74 TESCC patients was analyzed. Both the mtDNA copy number and mtDNA integrity were analyzed by quantitative real-time polymerase chain reaction (PCR). The hOGG1 Ser326Cys polymorphisms were identified by restriction fragment length polymorphism PCR and PCR-based direct sequencing.
  
  
  RESULTS
  Among noncancerous esophageal mucosa, cancerous TESCC nests, and metastatic lymph nodes, the mtDNA integrity decreased (95.2 to 47.9 to 18.6 %; P < 0.001) and the mtDNA copy number disproportionally increased (0.163 to 0.204 to 0.207; P = 0.026). In TESCC, higher indexes of cigarette smoking (0, 0-20, 20-40, and >40 pack-years) were related to an advanced pathologic N category (P = 0.038), elevated mtDNA copy number (P = 0.013), higher mtDNA copy ratio (P = 0.028), and increased mtDNA integrity (P = 0.069). The TESCC mtDNA integrity in patients with Ser/Ser, Ser/Cys, and Cys/Cys hOGG1 variants decreased stepwise from 65.2 to 52.1 to 41.3 % (P = 0.051).
  
  
  CONCLUSIONS
  Elevated 8-OHdG accumulations on mtDNA in TESCC were observed. Such accumulations were associated with a compensatory increase in total mtDNA copy number, indexes of cigarette smoking, and hOGG1 Ser326Cys polymorphisms.
authors.affiliation: Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan, doc2765c@ms59.hinet.net.
authors.forename: Chen-Sung
authors.initials: CS
authors.lastname: Lin
authors.forename: Liang-Shun
authors.initials: LS
authors.lastname: Wang
authors.forename: Teh-Ying
authors.initials: TY
authors.lastname: Chou
authors.forename: Wen-Hu
authors.initials: WH
authors.lastname: Hsu
authors.forename: Hui-Chen
authors.initials: HC
authors.lastname: Lin
authors.forename: Shu-Yu
authors.initials: SY
authors.lastname: Lee
authors.forename: Mau-Hua
authors.initials: MH
authors.lastname: Lee
authors.forename: Shi-Chuan
authors.initials: SC
authors.lastname: Chang
authors.forename: Yau-Huei
authors.initials: YH
authors.lastname: Wei
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000235:genetics* / Q000556:secondary; D045647:DNA Glycosylases / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D004947:Esophagus / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005838:Genotype; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D012907:Smoking / Q000009:adverse effects*; D013899:Thoracic Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology
chemical_list: D004272:DNA, Mitochondrial; C024829:8-hydroxyguanine; D006147:Guanine; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human