Genetic polymorphisms in mediators of inflammation and gastric precancerous lesions.
Chronic inflammation induced by Helicobacter pylori is a key process in gastric carcinogenesis. We hypothesized that genetic polymorphisms in important mediators of H. pylori-induced inflammation may influence the risk of developing various grades of precancerous lesions. We studied the associations between single nucleotide polymorphisms (SNPs) in cyclooxygenase 1 and 2 (PTGS1 and PTGS2), inducible nitric oxide synthase (NOS2A), interferon gamma (IFNG) and its receptor (IFNGR1), and risk of gastric precancerous lesions in a Venezuelan population characterized by high rates of H. pylori infection. We found no association of precancerous lesions with SNPs in PTGS1 and in IFNG. A nonsynonymous SNP of NOS2A (Ser608Leu) and an SNP located in the promoter of IFNGR1 (C-56T) were associated with higher risk of atrophic gastritis [odds ratio (OR)=1.37, 95% confidence interval (CI)=1.01-1.86, and OR=1.49, 95% CI=1.01-2.19, respectively]. Two SNPs of PTGS2 were associated with risk of dysplasia (OR=1.60, 95% CI=1.01-2.54, and OR=0.66, 95% CI=0.43-0.99). We conclude that genetic variability in the genes we studied does not play a major role in the early stages of gastric carcinogenesis.
Canzian
Federico
F
German Cancer Research Center (DKFZ), Heidelberg, Germany. f.canzian@dkfz.de
Franceschi
Silvia
S
Plummer
Martyn
M
van Doorn
Leen-Jan
LJ
Lu
Yanhui
Y
Gioia-Patricola
Lydie
L
Vivas
Jorge
J
Lopez
Gladys
G
Severson
Richard K
RK
Schwartz
Ann G
AG
Muñoz
Nubia
N
Kato
Ikuko
I
D000328:Adult; D000368:Aged; D051545:Cyclooxygenase 1 / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000235:genetics; D005260:Female; D016481:Helicobacter Infections / Q000150:complications* / Q000453:epidemiology; D016480:Helicobacter pylori; D006801:Humans; D007249:Inflammation; D007371:Interferon-gamma / Q000235:genetics; D008297:Male; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011230:Precancerous Conditions / Q000235:genetics; D017471:Receptors, Interferon / Q000235:genetics; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000382:microbiology*; D014687:Venezuela / Q000453:epidemiology; D000096743:Interferon gamma Receptor
D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor; C496319:NOS2 protein, human; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human