Allelic loss of the DNA repair gene OGG1 against oxidative damage in esophageal squamous cell carcinoma.
Esophageal tissue often undergoes oxidative damage from exposure to cigarettes and alcohol. The OGG1 gene plays a major role in maintaining genetic integrity by removing 8-oxoguanine (8-oxoG) in cellular DNA by way of the base excision repair pathway. The OGG1 gene is located at 3p26.2 of the human chromosome. Although deletion in the 3p region is frequently found in cases of esophageal cancer, few reports have focused on the allelic loss of the OGG1 gene. Using 24 samples of surgically-resected esophageal cancer tissue, we assessed the allelic loss of the OGG1 gene with a set of three microsatellite markers that flank the OGG1 gene. We compared the loss of homozygosity status for the OGG1 gene with clinicopathologic factors, as well as OGG1 expression and accumulation of 8-oxoG, which was estimated in an immunohistochemical study. Of 24 cases, 20 were suitable for determining OGG1 allelic loss. Allelic loss of OGG1 was observed in 6 of 20 (30%) cases. An inverse correlation between OGG1 allelic loss and OGG1 expression was weakly observed (p=0.051). In contrast, OGG1 allelic loss showed a positive correlation with 8-oxoG accumulation, although the correlation was not statistically significant (0.095). OGG1 allelic loss was observed in 30% of patients in our study, a lower frequency than that reported in other malignancies, and correlated with reduced OGG1 expression and 8-oxoG accumulation. These findings suggest that attenuated OGG1 expression contributes to 8-oxoG accumulation under oxidative stress, resulting in cancer development in the esophagus. Thus, OGG1 allelic loss is related to carcinogenesis by oxidative stress rather than cancer progression in esophageal cancer.
Hagiwara
Atsushi
A
Department of Surgery, Saga University Faculty of Medicine, Nabeshima 5-1-1, Saga 849-8501, Japan.
Kitajima
Yoshihiko
Y
Sato
Seiji
S
Miyazaki
Kohji
K
D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics*; D002454:Cell Differentiation; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics* / Q000378:metabolism; D004260:DNA Repair / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000201:enzymology / Q000235:genetics*; D004947:Esophagus / Q000201:enzymology; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D007124:Immunoenzyme Techniques; D019656:Loss of Heterozygosity; D008207:Lymphatic Metastasis; D018895:Microsatellite Repeats; D009361:Neoplasm Invasiveness; D018384:Oxidative Stress
C024829:8-hydroxyguanine; D006147:Guanine; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human