Document Detail


Polymorphisms of the TP53 codon 72 and WRN codon 1367 in individuals from Northern Brazil with gastric adenocarcinoma.
MedLine Citation:
PMID:  16362795     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Gastric cancer is the second most frequent type of neoplasia and also the second most common cause of death in the world. TP53 codon 72, which produces variant proteins with an arginine (Arg) or proline (Pro), has been reported to be associated with cancers of the lung, oesophagus, stomach and cervix. Werner's syndrome (WS) is a premature ageing disease caused by a mutation in the WRN gene. The WRN protein acts as a DNA helicase and as an exonuclease. WRN codon 1367 produces variant proteins with an Arg or cysteine (Cys). This polymorphism has been studied, in order to understand the clinical impact of the molecular variants in WS and in age-related disorders. In the present study, the TP53 codon 72 and the WRN codon 1367 polymorphisms were investigated in 54 gastric adenocarcinoma patients (31 diffuse-type and 25 intestinal-type) and 54 controls. DNA samples were extracted, and PCR-RFLP was utilised for genotyping TP53 codon 72 and WRN codon 1367. The allele frequencies of the TP53 polymorphism were: Arg=0.74 and Pro=0.26. The allele frequencies of the WRN polymorphism were: Cys=0.73 and Arg=0.27. The crude genotypic frequencies in gastric cancer patients were similar to those of the controls, but in the WRN codon 1367 polymorphisms the mean age tended to be higher in the Arg/Arg genotypes. There also was an association, although not statistically significant, between the presence of Helicobacter pylori and the genotypes Cys/Cys and Cys/Arg and a higher percentage of cardia cancer among the Arg/Arg genotypes, and of non-cardia cancer among genotypes Cys/Cys and Cys/Arg. These findings may be a reflection of differences in the interaction between WRN codon 1367 polymorphisms and local factors in the stomach. To our knowledge, this is the first study to examine a genetic polymorphism of the WRN gene in cancer. The precise mechanisms of action of the TP53 and WRN polymorphisms involved in the aetiopathogeny of this disease need further investigation.
Authors:
A S Khayat; L Lobo Gatti; E Moura Lima; P P de Assumpção; F J Nascimento Motta; M L Harada; C Casartelli; S L Marques Payão; M A Cardoso Smith; R R Burbano
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical and experimental medicine     Volume:  5     ISSN:  1591-8890     ISO Abbreviation:  Clin. Exp. Med.     Publication Date:  2005 Dec 
Date Detail:
Created Date:  2005-12-19     Completed Date:  2006-03-28     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  100973405     Medline TA:  Clin Exp Med     Country:  Italy    
Other Details:
Languages:  eng     Pagination:  161-8     Citation Subset:  IM    
Affiliation:
Laboratório de Citogenética Humana, Departamento de Biologia, Centro de Ciências Biológicas, Campus Universitário do Guamá, Universidade Federal do Pará, Av. Augusto Correa 01, 66075-900, Belém-Pará, Brazil.
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / genetics*
Base Sequence
Brazil
Codon*
DNA Helicases / genetics*
DNA Primers
Exodeoxyribonucleases
Genes, p53*
Humans
Polymerase Chain Reaction
Polymorphism, Genetic*
RecQ Helicases
Stomach Neoplasms / genetics*
Chemical
Reg. No./Substance:
0/Codon; 0/DNA Primers; EC 3.1.-/Exodeoxyribonucleases; EC 3.6.1.-/DNA Helicases; EC 3.6.1.-/RecQ Helicases; EC 3.6.1.-/WRN protein, human

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