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Glutathione S-transferase genotype and p53 mutations in adenocarcinoma of the small intestine

Pedersen, LN; Kaerlev, L; Teglbjaerg, PS; Olsen, J; Eriksson, Mikael LU ; Guenel, P; Ahrens, W; Ballard, T and Autrup, H (2003) In Scandinavian Journal of Gastroenterology 38(8). p.845-849
Abstract
Adenocarcinoma of the small intestine (ASI) is a rare disease of unknown aetiology. The glutathione S-transferase M1 (GSTM1) enzyme catalyses the detoxification of compounds involved in carcinogenesis of adenocarcinoma of the stomach, colon and lung, including constituents of tobacco smoke. We investigated a possible interaction between the lack of GSTM1 enzyme activity and the carcinogenic compounds of tobacco smoke. Based on the theory that certain carcinogens cause specific point mutations in the p53 gene we analysed by single strand conformation polymorphism (SSCP) and sequencing, p53 exon 5-8 of 52 samples of ASI collected in Sweden, Germany, France, Italy and Denmark between 1995 and 1997. The GSTM1 gene status was investigated by... (More)
Adenocarcinoma of the small intestine (ASI) is a rare disease of unknown aetiology. The glutathione S-transferase M1 (GSTM1) enzyme catalyses the detoxification of compounds involved in carcinogenesis of adenocarcinoma of the stomach, colon and lung, including constituents of tobacco smoke. We investigated a possible interaction between the lack of GSTM1 enzyme activity and the carcinogenic compounds of tobacco smoke. Based on the theory that certain carcinogens cause specific point mutations in the p53 gene we analysed by single strand conformation polymorphism (SSCP) and sequencing, p53 exon 5-8 of 52 samples of ASI collected in Sweden, Germany, France, Italy and Denmark between 1995 and 1997. The GSTM1 gene status was investigated by multiplex PCR. The prevalence of GSTM1 negative genotype among cases with ASI was 69% and higher than previous reports of 50% suggesting a higher risk of ASI among GSTM1 negative compared with GSTM1 positive subjects. A 'case-only' approach was used to address the combined association between the GSTM1 negative genotype and lifestyle exposures in patients with ASI. Using this method, heavy smokers (>20 pack-years) with the GSTM1 negative genotype had an odds ratio of 4.8; 95% confidence interval (CI) (0.6-38.7) for ASI as compared to smokers who expressed GSTM1. No similar association between alcohol consumption and ASI was found. No p53 mutations in exon 5-8 were found in these samples, but the method may not be sensitive enough to identify smaller differences. Thus p53 does not seem to be the target of carcinogens acting in the small intestine. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
small intestine, p53, GSTM1, alcohol, cancer, tobacco
in
Scandinavian Journal of Gastroenterology
volume
38
issue
8
pages
845 - 849
publisher
Taylor & Francis
external identifiers
  • wos:000184490800009
  • pmid:12940438
  • scopus:0041927821
ISSN
1502-7708
DOI
10.1080/00365520310003976
language
English
LU publication?
yes
id
32e3d430-ee3f-4eac-9e0a-10c656e161f2 (old id 304816)
date added to LUP
2007-09-20 09:12:15
date last changed
2017-01-01 07:26:34
@article{32e3d430-ee3f-4eac-9e0a-10c656e161f2,
  abstract     = {Adenocarcinoma of the small intestine (ASI) is a rare disease of unknown aetiology. The glutathione S-transferase M1 (GSTM1) enzyme catalyses the detoxification of compounds involved in carcinogenesis of adenocarcinoma of the stomach, colon and lung, including constituents of tobacco smoke. We investigated a possible interaction between the lack of GSTM1 enzyme activity and the carcinogenic compounds of tobacco smoke. Based on the theory that certain carcinogens cause specific point mutations in the p53 gene we analysed by single strand conformation polymorphism (SSCP) and sequencing, p53 exon 5-8 of 52 samples of ASI collected in Sweden, Germany, France, Italy and Denmark between 1995 and 1997. The GSTM1 gene status was investigated by multiplex PCR. The prevalence of GSTM1 negative genotype among cases with ASI was 69% and higher than previous reports of 50% suggesting a higher risk of ASI among GSTM1 negative compared with GSTM1 positive subjects. A 'case-only' approach was used to address the combined association between the GSTM1 negative genotype and lifestyle exposures in patients with ASI. Using this method, heavy smokers (>20 pack-years) with the GSTM1 negative genotype had an odds ratio of 4.8; 95% confidence interval (CI) (0.6-38.7) for ASI as compared to smokers who expressed GSTM1. No similar association between alcohol consumption and ASI was found. No p53 mutations in exon 5-8 were found in these samples, but the method may not be sensitive enough to identify smaller differences. Thus p53 does not seem to be the target of carcinogens acting in the small intestine.},
  author       = {Pedersen, LN and Kaerlev, L and Teglbjaerg, PS and Olsen, J and Eriksson, Mikael and Guenel, P and Ahrens, W and Ballard, T and Autrup, H},
  issn         = {1502-7708},
  keyword      = {small intestine,p53,GSTM1,alcohol,cancer,tobacco},
  language     = {eng},
  number       = {8},
  pages        = {845--849},
  publisher    = {Taylor & Francis},
  series       = {Scandinavian Journal of Gastroenterology},
  title        = {Glutathione S-transferase genotype and p53 mutations in adenocarcinoma of the small intestine},
  url          = {http://dx.doi.org/10.1080/00365520310003976},
  volume       = {38},
  year         = {2003},
}