Promoter methylation of cancer-related genes in gastric carcinoma.
Genetic changes associated with gastric cancer are not completely known, but epigenetic mechanisms involved in this disease seem to play an important role in its pathophysiology. One of these mechanisms, an aberrant methylation in the promoter regions of genes involved in cancer induction and promotion, may be of particular importance in gastric cancer.


OBJECTIVE
To analyze the methylation status of eight genes: Apaf-1, Casp8, CDH1, MDR1, GSTP1, BRCA1, hMLH1, Fas in gastric cancer patients.


METHODS
The methylation pattern of the genes was assessed by methylation specific restriction enzyme PCR (MSRE-PCR) in gastric tumors taken during surgery of 27 patients and compared with the methylation pattern in material obtained from biopsy in 25 individuals without cancer and pre-cancerous lesions.


RESULTS
We observed a promoter hypermethylation in the Casp8, hMLH1, CDH1 and MDR1 in gastric cancer patients as compared with the controls. Additionally, we investigated the relationship between promoter hypermethylation and age, gender, smoking and gastric cancer family history. The hypermethylation of the hMLH1 gene occurred more frequently in female than in men, and the hypermethylation of the CDH1 gene was observed preferentially in smoking than in non-smoking individuals.


CONCLUSIONS
The data obtained indicate that changes in DNA methylation may contribute to gastric carcinogenesis.
Poplawski
T
T
Department of Molecular Genetics, University of Lodz, Lodz, Poland.
Tomaszewska
K
K
Galicki
M
M
Morawiec
Z
Z
Blasiak
J
J
D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism*; D004247:DNA / Q000737:chemistry; D019175:DNA Methylation; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D020868:Gene Silencing; D006801:Humans; D008297:Male; D008745:Methylation; D008954:Models, Biological; D015233:Models, Statistical; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism*
D017931:DNA Primers; D004247:DNA