A polymorphism of C-to-T substitution at -31 IL1B is associated with the risk of advanced gastric adenocarcinoma in a Japanese population.
Proinflammatory cytokine gene polymorphisms have been demonstrated to associate with gastric cancer risk, of which IL1B-31T/C and -511C/T changes have been well investigated due to the possibility that they may alter the IL1B transcription. The signal transduction target upon interleukin 1 beta (IL1beta) stimulation, the nuclear factor of kappa B (NFkappaB) activation, supports cancer development, signal transduction in which is mediated by FS-7 cell-associated cell surface antigen (FAS) signaling. Based on recent papers describing the prognostic roles of the polymorphisms and the NFkappaB functions on cancer development, we sought to determine if Japanese gastric cancer patients were affected by the IL1B -31/-511 and FAS-670 polymorphisms. A case-control study was conducted on incident gastric adenocarcinoma patients (n=271) and age-gender frequency-matched control subjects (n=271). We observed strong linkage disequilibrium between the T allele at -511 and the C allele at -31 and between the C allele at -511 and the T allele at -31 in IL1B in both the cases and controls (R (2)=0.94). Neither IL1B-31, -511 nor FAS-670 polymorphisms showed significantly different risks of gastric adenocarcinoma. Though FAS-670 polymorphisms did not show any significant difference, the proportion of subjects with IL1B-31TT (or IL1B-511CC) increased according to stage (trend P=0.019). In particular, subjects with stage IV had a two times higher probability of having either IL1B-31TT (or IL1B-511CC) genotype compared with stage I subjects. These observations suggest that IL1B-31TT and IL1B-511CC are associated with disease progression.
Ikehara
Sanae Kabata
SK
Department of Epidemiology, Nagoya University Graduate School of Medicine, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.|Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
Ikehara
Yuzuru
Y
Division of Oncological Pathology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan. yikehara@aichi-cc.jp.
Matsuo
Keitaro
K
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
Hirose
Kaoru
K
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
Niwa
Toru
T
Division of Oncological Pathology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
Ito
Hidemi
H
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
Ito
Seiji
S
Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
Kodera
Yasuhiro
Y
Department of Surgery II, Nagoya University Graduate School of Medicine, Tsurumai-ku, Nagoya, Japan.
Yamamura
Yoshitaka
Y
Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
Nakanishi
Hayao
H
Division of Oncological Pathology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
Tatematsu
Masae
M
Division of Oncological Pathology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
Tajima
Kazuo
K
Department of Epidemiology, Nagoya University Graduate School of Medicine, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.|Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000483:Alleles; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D011110:Polymorphism, Genetic; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics*
D053583:Interleukin-1beta; D016328:NF-kappa B