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

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)S379-S388
JournalAnnals of Surgical Oncology
Volume20
Issue number3 SUPPL.
DOIs
Publication statusPublished - 2013

ASJC Scopus subject areas

  • Surgery
  • Oncology

Fingerprint

Dive into the research topics of 'Cigarette Smoking and hOGG1 Ser326Cys polymorphism are associated with 8-ohdg accumulation on mitochondrial dna in thoracic esophageal Squamous Cell Carcinoma'. Together they form a unique fingerprint.

Cite this