大腸直腸癌之基因與環境交互作用
Date Issued
2003-07-31
Date
2003-07-31
Author(s)
梁金銅
DOI
912314B002345
Abstract
The colorectal tumorigenesis involves the interaction between environmental and genetic
alterations. In this study, we further clarify this mechanism, i.e., the gene-environment
interaction, based on the previous study that early onset colorectal cancers (age of disease
onset less than 40 years old) tended to present with high fuquency microsatellite instability
(MSI-H), as compared with late onset counterparts (age of disease onset more than 60 years
old), with 29.4% and 6.3%, respectively (p＜0.001). However, further tracing family history
showed that there was no significant difference between these 2 groups of patients, with the
incidence of a positive family history of cancer 17.4% and 14.3%, respectively (p=0.0859).
This result implied that the early-onset colorectal cancers in Taiwan result predominantly
from environmental rather than familial germline alteration. In the present study, we further
analyze early onset colorectal cancers with MSI-H. The experimental methods included Western blotting of mismatch repair genes hMSH2 and hMLH1, and dHPLC analysis, direct
sequencing, and hypermethylation analysis of hMLH1 gene. We found that hMLH1protein was
negative in 63.0% (n=34), and hMSH2protein was negative in 3.7% (n=2), during the Western
blotting analysis. dHPLC and direct gene sequencing showed that genetic mutation of hMLH1
gene was present in 3 patients (5.6%), 28 (51.9%) of the remaining 31 patients presented with
hypermethylation on the promoter region of hMLH1, whereas the mechanism for altmations of
hMLH1 in the other 3 patients was unknown. This result implied that a subset of early onset
of colorectal cancer was through the carcinogenic pathway of MSI, and the hypermethylation
of hMLH1 promoter represented a major mechanism for the presentation of MSI-H in the
early-onset colorectal cancers of Taiwan. Therefore, we concluded that environmental factors
might be more important than genetic factors for the tumorigenesis of early onset colorectal
cancer in Taiwan.
Subjects
early onset colorectal cancer
MSI-H
hypermethylation
SDGs
Publisher
臺北市：國立臺灣大學醫學院外科
Type
report
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