Polymorphisms in TDG and MGMT Genes – Epidemiological and Functional Study in Lung Cancer Patients from Poland

Summary Functional genetic polymorphisms of DNA repair genes are good candidates for cancer susceptibility markers. We studied two genes coding for proteins removing small DNA adducts by direct repair (MGMT), or mispaired DNA bases by base excision repair (TDG). The non‐silent polymorphisms of MGMT...

Full description

Saved in:
Bibliographic Details
Published in:Annals of human genetics 2004-07, Vol.68 (4), p.300-312
Main Authors: Krześniak, M., Butkiewicz, D., Samojedny, A., Chorży, M., Rusin, M.
Format: Article
Language:English
Subjects:
Adult
Aged
alternative
Alternative Splicing
Amino Acid Sequence
Base Sequence
cancer susceptibility
Carcinoma, Non-Small-Cell Lung - epidemiology
Carcinoma, Non-Small-Cell Lung - genetics
Case-Control Studies
DNA repair
DNA, Complementary - genetics
enhancer
Enhancer Elements, Genetic
Exons - genetics
Humans
lung cancer
Lung Neoplasms - epidemiology
Lung Neoplasms - genetics
Male
MGMT
Middle Aged
Molecular Sequence Data
O-Methylguanine-DNA Methyltransferase - genetics
Poland - epidemiology
Polymorphism, Genetic
RNA, Messenger - genetics
SNP
splicing
TDG
Thymine DNA Glycosylase - genetics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Summary Functional genetic polymorphisms of DNA repair genes are good candidates for cancer susceptibility markers. We studied two genes coding for proteins removing small DNA adducts by direct repair (MGMT), or mispaired DNA bases by base excision repair (TDG). The non‐silent polymorphisms of MGMT (84:Phe, 143:Val, 178:Arg) and TDG (199:Ser, 367:Met), and the functional MGMT enhancer polymorphism, did not show any statistically significant association with lung cancer risk in our case‐control analysis, but due to the relatively small number of individuals, strong conclusions on cancer risk association or lack thereof cannot be made. Sequencing of the TDG cDNA has not revealed any novel polymorphism, but did find an alternatively spliced mRNA missing exon 2. Our search for polymorphisms within the promoter‐enhancer region of MGMT revealed three novel sequence variants. The functional significance of the previously published MGMT enhancer polymorphism (1099C‐>T) was assessed. The less frequent sequence variant of the enhancer was associated with a modest (16–64%), but statistically significant, increase of MGMT promoter‐enhancer activity in the studied cell lines. This work points to the importance of studying the expression‐regulating elements of genes, as they may contain functional polymorphisms with the potential for modulating risk of various diseases, including cancer.
ISSN:0003-4800
1469-1809
DOI:10.1046/j.1529-8817.2004.00079.x