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 journalArticle

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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
JournalAnnals of Surgical Oncology
Volume20
Issue number3 SUPPL.
DOIs
Publication statusPublished - 2013

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Mitochondrial DNA
Thorax
Smoking
human oxoguanine glycosylase 1
Esophageal Squamous Cell Carcinoma
Lymph Nodes
Polymerase Chain Reaction
Deoxyguanosine
Restriction Fragment Length Polymorphisms
Hydroxyl Radical
Real-Time Polymerase Chain Reaction

ASJC Scopus subject areas

  • Surgery
  • Oncology
  • Medicine(all)

Cite this

Cigarette Smoking and hOGG1 Ser326Cys polymorphism are associated with 8-ohdg accumulation on mitochondrial dna in thoracic esophageal Squamous Cell Carcinoma. / Lin, Chen Sung; Wang, Liang Shun; Chou, Teh Ying; Hsu, Wen Hu; Lin, Hui Chen; Lee, Shu Yu; Lee, Mau Hua; Chang, Shi Chuan; Wei, Yau Huei.

In: Annals of Surgical Oncology, Vol. 20, No. 3 SUPPL., 2013.

Research output: Contribution to journalArticle

Lin, Chen Sung ; Wang, Liang Shun ; Chou, Teh Ying ; Hsu, Wen Hu ; Lin, Hui Chen ; Lee, Shu Yu ; Lee, Mau Hua ; Chang, Shi Chuan ; Wei, Yau Huei. / Cigarette Smoking and hOGG1 Ser326Cys polymorphism are associated with 8-ohdg accumulation on mitochondrial dna in thoracic esophageal Squamous Cell Carcinoma. In: Annals of Surgical Oncology. 2013 ; Vol. 20, No. 3 SUPPL.
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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.",
author = "Lin, {Chen Sung} and Wang, {Liang Shun} and Chou, {Teh Ying} and Hsu, {Wen Hu} and Lin, {Hui Chen} and Lee, {Shu Yu} and Lee, {Mau Hua} and Chang, {Shi Chuan} and Wei, {Yau Huei}",
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T1 - Cigarette Smoking and hOGG1 Ser326Cys polymorphism are associated with 8-ohdg accumulation on mitochondrial dna in thoracic esophageal Squamous Cell Carcinoma

AU - Lin, Chen Sung

AU - Wang, Liang Shun

AU - Chou, Teh Ying

AU - Hsu, Wen Hu

AU - Lin, Hui Chen

AU - Lee, Shu Yu

AU - Lee, Mau Hua

AU - Chang, Shi Chuan

AU - Wei, Yau Huei

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

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