Purpose: Recently the theory has been developed that host genetic
factor affects interleukin (IL)-1β might exert an influence on the
divergent clinical outcomes. We evaluated the roles of H. pylori infection
and polymorphism of IL-1β in the carcinogenesis of gastric adenocarcinoma.
Methods: Gastric cancer tissues from 68 patients, peripheral blood
from 43 controls, and various gastric cancer cell lines (MKN45, MKN74,
SNU620, SNU638, SNU216, SNU601, and AGS) were used. Single nucleotide
polymorphism (SNP) of IL-1β-31 and the length of tandem repeat of IL-1RN
were analyzed by PCR and automatic DNA sequencer. IL-1β mRNA expressions
from gastric cancer tissues were measured using semiquantitative RT-PCR and
compared according to SNP of IL-1β-31. We also investigated the IL-1β-31
SNP from various cancer cell lines and measured IL-1β mRNA and protein
expressions using semiquantitative RT- PCR and ELISA. We constructed
reporter systems for IL-1β-31T/T and IL-1β-31C/C and the responses to
antigen PMA and H. pylori were compared. Results: We couldn’t find
any significant difference in the frequencies of IL-1β-31 SNP and IL-1RN
polymorphism between the gastric cancer and control groups. IL-1β mRNA and
protein expression were significantly more highly responsive to PMA at
IL-1β-31 T/T type as compared with those of C/T or C/C type when studied in
gastric cancer cell lines, although we couldn’t find any significant
difference of IL-1β mRNA expression according to IL-1β-31 SNP when studied
in gastric cancer tissue. When we compared the activities of reporter
systems, the basal luciferase activity, response to PMA, and response to H.
pylori of reporter genes was 1.30-fold, 1.32-fold, and 1.62-fold higher
respectively in pIL-1β T/T type as compared with pIL-1β C/C type.
Conclusions: These findings indicate that SNP of IL-1β exerts an
influence on the expression of IL-1β and there is a significant difference
in response to environmental factors. They also suggest that the host with
IL-1β-31 T/T type has a higher risk of hypochlorhydria, gastric atrophy,
and after all gastric cancer in response to H. pylori infection. However the
relationship between polymorphism of IL-1β and gastric adenocarcinoma
require further study.
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