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: Takashi Ando, Takeshi Ishikawa, Haruki Kato, Norimasa Yoshida, Yuji Naito, Satoshi Kokura, Nobuaki Yagi, Tomohisa Takagi, Osamu Handa, Jo Kitawaki, Naoto Nakamura, Goji Hasegawa, Michiaki Fukui, Eiko Imamoto, Chie Nakamura, Hirokazu Oyamada, Yutaka Isozaki, Naohito Matsumoto, Yasuyuki Nagao, Mika Okita, Yoshihiro Nakajima, Manabu Kurokawa, Masafumi Nukina, Mitsuhiro Ohta, Shigeto Mizuno, Masakazu Ogata, Hiroshi Obayashi, Hyohun Park, Yoshihiro Kitagawa, Koji Nakano, Toshikazu Yoshikawa
• Journal: International journal of cancer (Int J Cancer) Vol. 125 Issue 11 Pg. 2595-602 (Dec 01 2009) ISSN: 1097-0215 [Electronic] United States
• PMID: 19544559 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Cytokines
• HLA-D Antigens

Topics

• Aged
• Asian People (genetics)
• Case-Control Studies
• Cytokines (genetics)
• Drug Synergism
• Female
• Genotype
• HLA-D Antigens (genetics)
• Helicobacter Infections (genetics, microbiology)
• Helicobacter pylori (pathogenicity)
• Humans
• Male
• Middle Aged
• Polymorphism, Genetic (genetics)
• Risk Factors
• Stomach Neoplasms (genetics, microbiology)