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


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).


CONCLUSIONS
FAS and FASL genotypes of the hosts are important determinants in the pathogenesis of gastric atrophy and intestinal metaplasia in H. pylori-infected individuals.
Hsu
Ping-I
PI
Division of Gastroenterology and General Medicine, Department of Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung, Taiwan, R.O.C. williamhsup@yahoo.com.tw
Lu
Pei-Jung
PJ
Wang
E-Ming
EM
Ger
Luo-Ping
LP
Lo
Gin-Ho
GH
Tsay
Feng-Woei
FW
Chen
Tai-An
TA
Yang
Hsiao-Bai
HB
Chen
Hui-Chun
HC
Lin
Weir-Sen
WS
Lai
Kwok-Hung
KH
D000368:Aged; D053222:Fas Ligand Protein / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000150:complications; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D007414:Intestinal Neoplasms / Q000235:genetics / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011230:Precancerous Conditions / Q000235:genetics* / Q000382:microbiology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology; D019014:fas Receptor / Q000235:genetics*
C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D019014:fas Receptor