Abstract
Background
Recently, the association between gastric cancer risk and a functional polymorphism of Toll-like receptor 2 (TLR2), -196 to -174del, was reported for a Japanese population. This study aimed to confirm the associations of the polymorphism with the risk of gastric cancer, as well as Helicobacter pylori seropositivity and the risk of gastric atrophy in Japanese.
Methods
The study subjects were 583 histologically diagnosed gastric cancer patients and 1636 age- and sex-frequencymatched control outpatients who visited Aichi Cancer Center Hospital from the years 2001 to 2005. Serum anti-H. pylori IgG antibody and pepsinogens were measured to evaluate H. pylori infection and gastric atrophy, respectively. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by a logistic model.
Results
The age- and sex-adjusted ORs of gastric cancer were 1.13 (95% CI: 0.88–1.46) for ins/del, 1.17 (95% CI: 0.79–1.73) for del/del, and 1.14 (95% CI: 0.89–1.45) for ins/del + del/del, relative to the ins/ins genotype compared with gastric atrophy controls; none of these findings were statistically significant. The TLR2 -196 to 174del polymorphism was not significantly associated with either H. pylori seropositivity or gastric atrophy.
Conclusion
Our study did not reproduce the association between gastric cancer risk and the TLR2 -196 to -174del polymorphism in Japanese. Further examinations with sufficient numbers of study subjects are required to verify our findings.
Article PDF
Similar content being viewed by others
Explore related subjects
Discover the latest articles and news from researchers in related subjects, suggested using machine learning.Avoid common mistakes on your manuscript.
References
Parkin DM, Whelan SL, Ferlay J, Raymond L, Young J. Cancer incidence in five continents, volume VII. Lyon: IARC Press; 1997.
Parkin DM, Pisani P, Ferlay J. Estimates of the worldwide incidence of 25 major cancers in 1990. Int J Cancer 1999;80:827–841.
Hamilton SR, Aaltonen LA. Pathology and genetics. Tumours of the digestive system. WHO classification of tumours. Lyon: IARC Press; 2000.
Tsuji S, Tsujii M, Murata H, Nishida T, Komori M, Yasumaru M, et al. Helicobacter pylori eradication to prevent gastric cancer: underlying molecular and cellular mechanisms. World J Gastroenterol 2006;12:1671–1680.
Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M, et al. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med 2001;345:784–779.
El-Omar EM, Rabkin CS, Gammon MD, Vaughan TL, Risch HA, Schoenberg JB, et al. Increased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms. Gastroenterology 2003;124:1193–1201.
Machado JC, Figueiredo C, Canedo P, Pharoah P, Carvalho R, Nabais S, et al. A proinflammatory genetic profile increases the risk for chronic atrophic gastritis and gastric carcinoma. Gastroenterology 2003;125:364–371.
Leulier F, Lemaitre B. Toll-like receptors-taking an evolutionary approach. Nat Rev Genet 2008;9:165–178.
Kawai T, Akira S. TLR signaling. Cell Death Differ 2006;13:816–825.
Takeda K, Kaisho T, Akira S. Toll-like receptors. Annu Rev Immunol 2003;21:335–376.
Smith MF Jr, Mitchell A, Li G, Ding S, Fitzmaurice AM, Ryan K, et al. Toll-like receptor (TLR) 2 and TLR5, but not TLR4, are required for Helicobacter pylori-induced NF-kappa B activation and chemokine expression by epithelial cells. J Biol Chem 2003;278:32552–32560.
Tahara T, Arisawa T, Wang F, Shibata T, Nakamura M, Sakata M, et al. Toll-like receptor 2 -196 to 174del polymorphism influences the susceptibility of Japanese people to gastric cancer. Cancer Sci 2007;98:1790–1794.
Tajima K, Hirose K, Inoue M, Takezaki T, Hamajima N, Kuroishi T. A model of practical cancer prevention for out-patients visiting a hospital: the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC). Asian Pac J Cancer Prev 2000;1:35–47.
Hishida A, Matsuo K, Goto Y, Mitsuda Y, Hiraki A, Naito M, et al. No association between AICDA 7888 C/T polymorphism, Helicobacter pylori seropositivity, and the risk of atrophic gastritis and gastric cancer in Japanese. Gastric Cancer 2010;13:43–49.
Goto Y, Hishida A, Matsuo K, Tajima K, Morita E, Naito M, et al. PRKCH gene polymorphism is associated with the risk for severe gastric atrophy. Gastric Cancer 2010;13:90–94.
Inoue M, Tsugane S. Epidemiology of gastric cancer in Japan. Postgrad Med J 2005;81:419–424.
Tahara T, Arisawa T, Wang F, Shibata T, Nakamura M, Sakata M, et al. Toll-like receptor 2 (TLR) -196 to 174del polymorphism in gastro-duodenal diseases in Japanese population. Dig Dis Sci 2008;53:919–924.
El-Omar EM, Ng MT, Hold GL. Polymorphisms in Toll-like receptor genes and risk of cancer. Oncogene 2008;27:244–252.
Pasare C, Medzhitov R. Toll-like receptors: linking innate and adaptive immunity. Adv Exp Med Biol 2005;560:11–18.
Kawahara T, Kuwano Y, Teshima-Kondo S, Sugiyama T, Kawai T, Nikawa T, et al. Helicobacter pylori lipopolysaccharide from type I, but not type II strains, stimulates apoptosis of cultured gastric mucosal cells. J Med Invest 2001;48:167–174.
Kawahara T, Teshima S, Oka A, Sugiyama T, Kishi K, Rokutan K. Type I Helicobacter pylori lipopolysaccharide stimulates toll-like receptor 4 and activates mitogen oxidase 1 in gastric pit cells. Infect Immun 2001;69:4382–4389.
Schmausser B, Andrulis M, Endrich S, Lee SK, Josenhans C, Müller-Hermelink HK, et al. Expression and subcellular distribution of toll-like receptors TLR4, TLR5 and TLR9 on the gastric epithelium in Helicobacter pylori infection. Clin Exp Immunol 2004;136:521–526.
Uno K, Kato K, Atsumi T, Suzuki T, Yoshitake J, Morita H, et al. Toll-like receptor (TLR) 2 induced through TLR4 signaling initiated by Helicobacter pylori cooperatively amplifies iNOS induction in gastric epithelial cells. Am J Physiol Gastrointest Liver Physiol 2007;293:1004–1012.
Noguchi E, Nishimura F, Fukai H, Kim J, Ichikawa K, Shibasaki M, et al. An association study of asthma and total serum immunoglobin E levels for Toll-like receptor polymorphisms in a Japanese population. Clin Exp Allergy 2004;34:177–183.
Ito Y, Azuma T, Ito S, Miyaji H, Hirai M, Yamazaki Y, et al. Analysis and typing of the vacA gene from cagA-positive strains of Helicobacter pylori isolated in Japan. J Clin Microbiol 1997;35:1710–1714.
Azuma T. Helicobacter pylori CagA protein variation associated with gastric cancer in Asia. J Gastroenterol 2004;39:97–103.
Zhou W, Yamazaki S, Yamakawa A, Ohtani M, Ito Y, Keida Y, et al. The diversity of vacA and cagA genes of Helicobacter pylori in East Asia. FEMS Immunol Med Microbiol 2004;40:81–87.
Miki K, Ichinose M, Shimizu A, Huang SC, Oka H, Furihata C, et al. Serum pepsinogens as a screening test of extensive chronic gastritis. Gastroenterol Jpn 1987;22:133–141.
Biemond I, Kreuning J, Jansen JB, Lamers CB. Serum pepsinogens in patients with gastric diseases or after gastric surgery. Scand J Gastroenterol 1994;29:238–242.
Oksanen A, Sipponen P, Miettinen A, Sarna S, Rautelin H. Evaluation of blood tests to predict normal gastric mucosa. Scand J Gastroenterol 2000;35:791–795.
Yanaoka K, Oka M, Mukoubayashi C, Yoshimura N, Enomoto S, Iguchi M, et al. Cancer high-risk subjects identified by serum pepsinogen tests: outcomes after 10-year follow-up in asymptomatic middle-aged males. Cancer Epidemiol Biomarkers Prev 2008;17:838–845.
Inoue M, Kobayashi S, Matsuura A, Hamajima N, Tajima K, Tominaga S. Agreement of endoscopic findings and serum pepsinogen levels as an indicator of atrophic gastritis. Cancer Epidemiol Biomarkers Prev 1998;7:261–263.
Suzuki H, Hibi T, Marshall BJ. Helicobacter pylori: present status and future prospects in Japan. J Gastroenterol 2007;42:1–15.
Sasazuki S, Inoue M, Iwasaki M, Otani T, Yamamoto S, Ikeda S, et al. Effect of Helicobacter pylori infection combined with CagA and pepsinogen status on gastric cancer development among Japanese men and women: a nested case-control study. Cancer Epidemiol Biomarkers Prev 2006;15:1341–1347.
Lauren P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal type carcinoma. Acta Pathol Microbiol Scand 1965;64:31–49.
Craanen ME, Dekker W, Blok P, Ferwerda J, Tytgat GN. Intestinal metaplasia and Helicobacter pylori: an endoscopic bioptic study of the gastric antrum. Gut 1992;33:16–20.
McColl KE. Cancer of the gastric cardia. Best Pract Res Clin Gastroenterol 2006;20:687–696.
HapMap. http://www.hapmap.org. Accessed 1 Jul 2010.
dbSNP. http://www.ncbi.nlm.nih.gov/snp. Accessed 1 Jul 2010
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hishida, A., Matsuo, K., Goto, Y. et al. No associations of Toll-like receptor 2 (TLR2) -196 to -174del polymorphism with the risk of Helicobacter pylori seropositivity, gastric atrophy, and gastric cancer in Japanese. Gastric Cancer 13, 251–257 (2010). https://doi.org/10.1007/s10120-010-0567-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10120-010-0567-y