基因修補酵素XRCC1與hOGG1與食道癌關係之研究(1/2)
Date Issued
2003-07-31
Date
2003-07-31
Author(s)
李章銘
DOI
912314B002231
Abstract
The risk to develop esophageal cancer is associated with a variety of
environmental and genetic factors. Previously, we have found that individual
susceptibility to esophageal cancer in Taiwan was closely related to the consumption
of tobacco, alcohol and areca. These factors exerted a synergistic effect on the risk
for esophageal cancer. On the other hand, the genetic variation was also found
important in determining the individual susceptibility to esophageal cancer. Genetic
polymorphisms of the xenobiotic metabolizing enzymes, GSTP1, GSTT1, and
CYP1A1, tumor suppressor gene, p53, or DNA repair enzymes, XRCC1 or hOGG1,
can significantly influence the risk of esophageal cancer. Given that the DNA
damage is the common form induced by the environmental carcinogens and the main
contributor to esophageal carcinogenesis, the individual variation in the repairing
capacity for damaged DNA would play a important role in determine the tendency for
individual carcinogenesis of the esophagus. Therefore, the aim of this study was to
investigate whether the genetic alteration of the DNA repair genes, hOGG1, and
XRCC1 can modify the individual risk to esophageal cancer. Previously, we have
developed the technique of laser capture microdissection (LCM) to obtain pure tumor
DNA for analysis. Using this technique, we have alleotyping the hOGG1 on intron 4
and exon 7, where the genetic polymorphisms locates. We also genotyped the
patients of esophageal cancer for the hOGG1 Ser 326 Cys genetic polymorphism on
intron 7. The expression of the hOGG1 in tumor was also examined by
immunohistochemical staining. Totally, we evaluated the status of LOH in tumor
from 90 patients. Sixty-seven of them further received immunohistochemical
staining for the hOGG1 expression. 204 patients and 266 normal control received
genotyping for the hOGG1 polymorphisms. We found that, the risk for the
esophageal cancer was enhanced by the presence of the hOGG1 326 Cys allele in the
males who did not regularly consume tobacco, alcohol, or areca nut, with ORs(95%
CI) being 3.09 (1.22-7.81) for the non-smokers, 2.40 (1.08-5.31) for the non-alcohol
drinkers, and 1.86 (0.99-3.49) for the non-areca chewers. We also found the allelic
loss in genetic locus of hOGG1 is a very common episode with 62.2% of cases on the
intron 4 and 56.7% of cases on the exon 7. The expression of the hOGG1 in the
tumor tissue were also reduced, with 82% of the patients having tumor without
expressing or expressing only a very low level of hOGG1 (less than 10% of the tumor
cells). This implies that repair of the oxidative damaged DNA, 8-oxoG, is an
important mechanism for prevention of neoplasm in the esophagus. Through the
genetic variation produced by the polymorphism, the function of the hOGG1 might
have a further detriment once allele was lost under the continuous challenge of the
DNA damage. Therefore hOGG1 is an important tumor suppressor gene for the
esophageal carcinogenesis.
Subjects
Esophageal cancer
hOGG1
Polymorphism
SDGs
Publisher
臺北市：國立臺灣大學醫學院外科
Type
report
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