Cigarette Smoking and hOGG1 Ser326Cys polymorphism are associated with 8-ohdg accumulation on mitochondrial dna in thoracic esophageal Squamous Cell Carcinoma

Chen Sung Lin, Liang Shun Wang, Teh Ying Chou, Wen Hu Hsu, Hui Chen Lin, Shu Yu Lee, Mau Hua Lee, Shi Chuan Chang, Yau Huei Wei

研究成果: 雜誌貢獻文章

15 引文 斯高帕斯(Scopus)

摘要

Background. We examined whether cigarette smoking affects the degrees of oxidative damage (8-hydroxyl-20- 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.

原文英語
期刊Annals of Surgical Oncology
20
發行號3 SUPPL.
DOIs
出版狀態已發佈 - 2013

ASJC Scopus subject areas

  • Surgery
  • Oncology
  • Medicine(all)

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