Genetic polymorphisms in anti-inflammatory cytokine signaling and the prevalence of gastric precancerous lesions in Venezuela.
OBJECTIVE
The aim of the study was to assess the effects of genetic polymorphisms in anti-inflammatory mediators, i.e., IL10, IL4 and IL4R on the prevalence of gastric precancerous lesions and their interactions with other environmental factors.


METHODS
The study population consisted of 2,033 Venezuelan subjects known to have extremely high Helicobacter Pylori (HP) infection rates. The odds ratios (OR) and 95% confidence intervals (CI) associated with these polymorphisms were estimated by multinominal logistic regression models for gastric precursor lesions.


RESULTS
We found a 60% increase in risk of intestinal metaplasia (IM) and dysplasia combined (OR 1.62, 95% CI: 1.10-2.38) among the carriers of the IL10-1082 low activity allele. This increased risk was more pronounced for dysplasia than for IM. On the other hand, homozygotes with the low activity allele of the A398G polymorphism in the IL4R gene had a modest increase in risk of atrophic gastritis (OR = 1.52, 95% CI: 1.05-2.21), compared with homozygotes of the high activity allele. There were no statistically significant synergetic interactions between these polymorphisms and environmental risk factors (low fruit intake, high starchy vegetable intake and cigarette smoking) for these lesions.


CONCLUSIONS
While the results of the present study suggest roles of genetic variability in these anti-inflammatory mediators in different stages of gastric carcinogenesis, there is high likelihood that they were chance findings due to multiple comparisons.
Kato
Ikuko
I
Karmanos Cancer Institute, 110 East Warren Avenue, Detroit, MI, 48201, USA. katoi@med.wayne.edu
Canzian
Federico
F
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
D000328:Adult; D000368:Aged; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005756:Gastritis / Q000453:epidemiology / Q000235:genetics / Q000382:microbiology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D016481:Helicobacter Infections / Q000150:complications / Q000453:epidemiology / Q000382:microbiology; D016480:Helicobacter pylori / Q000235:genetics; D006801:Humans; D018836:Inflammation Mediators; D016753:Interleukin-10 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D007422:Intestines / Q000382:microbiology / Q000473:pathology; D016015:Logistic Models; D008297:Male; D008679:Metaplasia; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011230:Precancerous Conditions / Q000453:epidemiology / Q000235:genetics* / Q000382:microbiology; D015995:Prevalence; D019948:Receptors, Interleukin-4 / Q000235:genetics; D018570:Risk Assessment; D012307:Risk Factors; D015398:Signal Transduction / Q000235:genetics*; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000382:microbiology; D014687:Venezuela / Q000453:epidemiology
D016207:Cytokines; D018836:Inflammation Mediators; D019948:Receptors, Interleukin-4; D016753:Interleukin-10; D015847:Interleukin-4