Polymorphisms of death pathway genes FAS and FASL and risk of premalignant gastric lesions.

Abstract:

BACKGROUND:Tumorigenesis is a multistep process that begins with the abrogation of normal controls of apoptosis and cell proliferation, and the FAS receptor-ligand system is a key regulator of apoptosis. The aim of this study was to investigate whether functional polymorphisms of death pathway genes (FAS and FASL) are associated with the development of gastric atrophy and intestinal metaplasia. PATIENTS AND METHODS:Genotypes in the promoter regions of the FAS (-1377G/A and -670A/G) and FASL (-844T/C) genes of 101 healthy individuals and 86 gastric cancer patients were determined by PCR-RFLP. Additionally, gastric histological changes were examined according to the updated Sydney System. RESULTS:The carriage of FASL -844C allele significantly increased the risk of atrophy in the gastric corpus, with an adjusted odds ratio (OR) of 5.0 [95% confidence interval (CI), 1.5-6.8]. There were no gene-gene interactions among FASL -844T/C, FAS -1377G/A and FAS -670A/G polymorphisms in developing premalignant gastric lesions. In the 109 individuals with Helicobacterpylori infection, carrying the FAS -1377A allele was a protective factor for developing intestinal metaplasia in the antrum (OR, 0.3; 95% CI, 0.1-0.9), while carrying the FASL -844C allele was a risk factor for developing gastric atrophy in the corpus (OR, 9.4; 95% CI, 1.7-53.4). CONCLUSION:FAS and FASL genotypes of the hosts are important determinants in the pathogenesis of gastric atrophy and intestinal metaplasia in H. pylori-infected individuals.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Hsu PI,Lu PJ,Wang EM,Ger LP,Lo GH,Tsay FW,Chen TA,Yang HB,Chen HC,Lin WS,Lai KH

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

97-103

issue

1A

eissn

0250-7005

issn

1791-7530

journal_volume

28

pub_type

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