title: Synergistic effect of HLA class II loci and cytokine gene polymorphisms on the risk of gastric cancer in Japanese patients with Helicobacter pylori infection.
abstract: It has been reported that polymorphisms of human leukocyte antigen (HLA) genes and several cytokine genes are associated with an increased risk of developing gastric cancer (GC). However, the results of studies from different geographic regions, ethnic groups and study groups are inconsistent. The aim of this study was to evaluate the influence of H. pylori infection and host genetic factors on GC susceptibility in Japanese patients with GC. We analyzed genotypes for HLA class I and II, tumor necrosis factor alpha, interleukin (IL)-1beta, IL-1 receptor, IL-4, IL-4Ralpha and IL-10 in 330 H. pylori-infected noncardia patients with GC and 190 H. pylori-infected nonulcer dyspeptic controls. Haplotype analyses indicated that the frequencies of the HLA DRB1*0405 and DQB1*0401 alleles were increased in the patients with intestinal-type GC when compared with controls (both DRB1*0405 and DQB1*0401: p = 0.015, OR = 1.57, 95% CI = 1.09-2.26), but the changes were not statistically significant after correction for multiple comparisons. None of the cytokine gene polymorphisms were associated with GC susceptibility, whether patients with GC were analyzed as a group according to the histological subtype. Of interest was the comparison of controls and patients with intestinal-type GC. The frequency of an IL-10-592AA homozygote showing concomitant carriage of the HLA DRB1*0405-DQB1*0401 haplotype was significantly higher in patients with intestinal-type GC (chi(2) = 6.369, p = 0.0116, p(c) = 0.0464, OR = 2.43, 95% CI = 1.21-4.48). Our results suggest that the HLA class II and IL-10-592A/C polymorphisms synergistically affect the susceptibility to GC development of H. pylori-infected individuals in the Japanese population.
authors: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. t-ando@yellow.plala.or.jp
authors: Takashi
authors: T
authors: Ando
authors: Takeshi
authors: T
authors: Ishikawa
authors: Haruki
authors: H
authors: Kato
authors: Norimasa
authors: N
authors: Yoshida
authors: Yuji
authors: Y
authors: Naito
authors: Satoshi
authors: S
authors: Kokura
authors: Nobuaki
authors: N
authors: Yagi
authors: Tomohisa
authors: T
authors: Takagi
authors: Osamu
authors: O
authors: Handa
authors: Jo
authors: J
authors: Kitawaki
authors: Naoto
authors: N
authors: Nakamura
authors: Goji
authors: G
authors: Hasegawa
authors: Michiaki
authors: M
authors: Fukui
authors: Eiko
authors: E
authors: Imamoto
authors: Chie
authors: C
authors: Nakamura
authors: Hirokazu
authors: H
authors: Oyamada
authors: Yutaka
authors: Y
authors: Isozaki
authors: Naohito
authors: N
authors: Matsumoto
authors: Yasuyuki
authors: Y
authors: Nagao
authors: Mika
authors: M
authors: Okita
authors: Yoshihiro
authors: Y
authors: Nakajima
authors: Manabu
authors: M
authors: Kurokawa
authors: Masafumi
authors: M
authors: Nukina
authors: Mitsuhiro
authors: M
authors: Ohta
authors: Shigeto
authors: S
authors: Mizuno
authors: Masakazu
authors: M
authors: Ogata
authors: Hiroshi
authors: H
authors: Obayashi
authors: Hyohun
authors: H
authors: Park
authors: Yoshihiro
authors: Y
authors: Kitagawa
authors: Koji
authors: K
authors: Nakano
authors: Toshikazu
authors: T
authors: Yoshikawa
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics*; D004357:Drug Synergism; D005260:Female; D005838:Genotype; D006681:HLA-D Antigens / Q000235:genetics*; D016481:Helicobacter Infections / Q000235:genetics* / Q000382:microbiology; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology
chemical_list: D016207:Cytokines; D006681:HLA-D Antigens