Interleukin 1B and interleukin 1RN polymorphisms are associated with increased risk of gastric carcinoma.
OBJECTIVE
Interleukin (IL)-1 gene cluster proinflammatory polymorphisms have been associated with development of gastric atrophy and with increased risk of gastric carcinoma. We aimed to determine the association between IL-1 loci polymorphisms and increased risk of gastric carcinoma in samples from a Portuguese population, and to find whether there was any relationship with the histologic types of gastric carcinoma.


METHODS
In a case-control study including 220 controls and 152 patients with gastric carcinoma (intestinal, 76; diffuse, 37; and atypical, 39), both the IL-1B-511 biallelic polymorphism and the IL-1RN penta-allelic variable number of tandem repeats were genotyped.


RESULTS
We found a significant association between the IL-1 polymorphisms and increased risk for tumor development in patients with intestinal-type gastric carcinoma. A trend towards an increased risk of tumor development was also observed in patients with diffuse-type gastric carcinoma. No significant relationship was observed in patients with atypical carcinoma. Carriers of IL-1B-511T and IL-1RN*2 homozygotes had increased risk for developing intestinal-type gastric carcinoma with odds ratios of 2.7 (95% confidence interval [CI], 1.5-4.9) and 3.1 (95% CI, 1.5-6.5), respectively. Statistical analysis showed an interaction between the 2 loci with the risk conferred by the IL-1B-511T allele substantially increased (odds ratio, 9.0; 95% CI, 3.5-23.0) in individuals homozygous for the IL-1RN*2 allele.


CONCLUSIONS
Our results provide further support to the association between IL-1 gene cluster proinflammatory polymorphisms and increased risk of gastric carcinoma. Furthermore, we found evidence pointing to the existence of a synergistic interaction between the IL-1B and IL-1RN polymorphisms.
Machado
J C
JC
Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal. josem@ipatimup.pt
Pharoah
P
P
Sousa
S
S
Carvalho
R
R
Oliveira
C
C
Figueiredo
C
C
Amorim
A
A
Seruca
R
R
Caldas
C
C
Carneiro
F
F
Sobrinho-Simões
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D007414:Intestinal Neoplasms / Q000235:genetics; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D011110:Polymorphism, Genetic; D011174:Portugal / Q000453:epidemiology; D012016:Reference Values; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics*
D007375:Interleukin-1