Skip to main content
Top
Published in: BMC Cancer 1/2007

Open Access 01-12-2007 | Research article

Assessment of the toll-like receptor 4 Asp299Gly, Thr399Ile and interleukin-8 -251 polymorphisms in the risk for the development of distal gastric cancer

Authors: Elvira Garza-Gonzalez, Francisco J Bosques-Padilla, Sandra I Mendoza-Ibarra, Juan P Flores-Gutierrez, Hector J Maldonado-Garza, Guillermo I Perez-Perez

Published in: BMC Cancer | Issue 1/2007

Login to get access

Abstract

Background

The intensity of the inflammation induced by Helicobacter pylori colonization is associated with the development of distal gastric cancer (GC). The host response to H. pylori has been related to genetic polymorphisms that influence both innate and adaptive immune responses.
Our aim was to investigate whether the presence of the TLR4 Asp299Gly, TLR4 Thr399Ile and IL-8-251 A/T polymorphisms had any influence in the development of distal GC in a Mexican population.

Methods

We studied 337 patients that were divided in two groups: 78 patients with histologically confirmed distal GC and 259 non-cancer controls. The presence of H. pylori in the control population was defined by positive results of at least two of four diagnostic tests: serology, histology, rapid urease test and culture. Human DNA was purified and genotyped for TLR4 Asp299Gly polymorphism by pyrosequencing, for TLR4 Thr399Ile by PCR-RFLP and for IL8-251 by the amplification refractory mutation system (ARMS)-PCR.

Results

The non-cancer control group was found to be in Hardy-Weinberg equilibrium at the polymorphic loci studied (chi-square H-W = 0.58 for IL8-251, 0.42 for TLR4 Asp299Gly and 0.17 for TLR4 Thr399Ile). The frequencies of mutated alleles (homozygous plus heterozygous) were compared between cases and controls. We found no significant difference for TLR4- Asp299Gly [the 7.7% of distal GC patients and 7.7 % non-cancer controls (p = 0.82)] and for TLR4 Thr399Ile [the 1.3% of GC patients and the 5% of the control population (p = 0.2)]. In contrast, for IL-8-251 A/T, 80.77% of the GC patients and 66.4% in the control group age and gender matched had at least one copy of mutated allele (OR = 2.12, 95% CI = 1.1–4.2) (p = 0.023).

Conclusion

This study showed that the IL8-251*A allele could be related to the development of distal gastric cancer in this Mexican population.
Literature
2.
go back to reference Rad R, Dossumbekova A, Neu B, Lang R, Bauer S, Saur D, Gerhard M, Prinz C: Cytokine gene polymorphisms influence mucosal cytokine expression, gastric inflammation, and host specific colonization during Helicobacter pylori infection. Gut. 2004, 53: 1082-1089. 10.1136/gut.2003.029736.CrossRefPubMedPubMedCentral Rad R, Dossumbekova A, Neu B, Lang R, Bauer S, Saur D, Gerhard M, Prinz C: Cytokine gene polymorphisms influence mucosal cytokine expression, gastric inflammation, and host specific colonization during Helicobacter pylori infection. Gut. 2004, 53: 1082-1089. 10.1136/gut.2003.029736.CrossRefPubMedPubMedCentral
3.
go back to reference Ferrero RL: Innate immune recognition of the extracellular mucosal pathogen, Helicobacter pylori. Mol Immunol. 2005, 42: 879-485. 10.1016/j.molimm.2004.12.001.CrossRefPubMed Ferrero RL: Innate immune recognition of the extracellular mucosal pathogen, Helicobacter pylori. Mol Immunol. 2005, 42: 879-485. 10.1016/j.molimm.2004.12.001.CrossRefPubMed
4.
go back to reference Schroder NW, Schumann RR: Single nucleotide polymorphisms of Toll-like receptors and susceptibility to infectious disease. Lancet Infect Dis. 2005, 5: 156-164.CrossRefPubMed Schroder NW, Schumann RR: Single nucleotide polymorphisms of Toll-like receptors and susceptibility to infectious disease. Lancet Infect Dis. 2005, 5: 156-164.CrossRefPubMed
5.
go back to reference Perez-Perez GI, Garza-Gonzalez E, Portal C, Olivares AZ: Role of cytokine polymorphisms in the risk of distal gastric cancer development. Cancer Epidemiol Biomarkers Prev. 2005, 14: 1869-1873. 10.1158/1055-9965.EPI-04-0889.CrossRefPubMed Perez-Perez GI, Garza-Gonzalez E, Portal C, Olivares AZ: Role of cytokine polymorphisms in the risk of distal gastric cancer development. Cancer Epidemiol Biomarkers Prev. 2005, 14: 1869-1873. 10.1158/1055-9965.EPI-04-0889.CrossRefPubMed
6.
go back to reference El-Omar EM, Carrington M, Chow WH, McColl KE, Bream JH, Young HA, Herrera J, Lissowska J, Yuan CC, Rothman N, Lanyon G, Martin M, Fraumeni JF, Rabkin CS: Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature. 2000, 404: 398-402. 10.1038/35006081.CrossRefPubMed El-Omar EM, Carrington M, Chow WH, McColl KE, Bream JH, Young HA, Herrera J, Lissowska J, Yuan CC, Rothman N, Lanyon G, Martin M, Fraumeni JF, Rabkin CS: Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature. 2000, 404: 398-402. 10.1038/35006081.CrossRefPubMed
7.
go back to reference Garza-Gonzalez E, Bosques-Padilla FJ, El-Omar E, Hold G, Tijerina-Menchaca R, Maldonado-Garza HJ, Perez-Perez GI: Role of the polymorphic IL-1B, IL-1RN and TNF-A genes in distal gastric cancer in Mexico. Int J Cancer. 2005, 114: 237-241. 10.1002/ijc.20718.CrossRefPubMed Garza-Gonzalez E, Bosques-Padilla FJ, El-Omar E, Hold G, Tijerina-Menchaca R, Maldonado-Garza HJ, Perez-Perez GI: Role of the polymorphic IL-1B, IL-1RN and TNF-A genes in distal gastric cancer in Mexico. Int J Cancer. 2005, 114: 237-241. 10.1002/ijc.20718.CrossRefPubMed
8.
go back to reference Camorlinga-Ponce M, Aviles-Jimenez F, Cabrera L, Hernandez-Pando R, Munoz O, Soza J, Torres J: Intensity of inflammation, density of colonization and interleukin-8 response in the gastric mucosa of children infected with Helicobacter pylori. Helicobacter. 2003, 8: 554-560. 10.1046/j.1523-5378.2003.00176.x.CrossRefPubMed Camorlinga-Ponce M, Aviles-Jimenez F, Cabrera L, Hernandez-Pando R, Munoz O, Soza J, Torres J: Intensity of inflammation, density of colonization and interleukin-8 response in the gastric mucosa of children infected with Helicobacter pylori. Helicobacter. 2003, 8: 554-560. 10.1046/j.1523-5378.2003.00176.x.CrossRefPubMed
9.
go back to reference Lee WP, Tai DI, Lan KH, Li AF, Hsu HC, Lin EJ, Lin YP, Sheu ML, Li CP, Chang FY, Chao Y, Yen SH, Lee SD: The -251T allele of the interleukin-8 promoter is associated with increased risk of gastric carcinoma featuring diffuse-type histopathology in Chinese population. Clin Cancer Res. 2005, 11: 6431-6441. 10.1158/1078-0432.CCR-05-0942.CrossRefPubMed Lee WP, Tai DI, Lan KH, Li AF, Hsu HC, Lin EJ, Lin YP, Sheu ML, Li CP, Chang FY, Chao Y, Yen SH, Lee SD: The -251T allele of the interleukin-8 promoter is associated with increased risk of gastric carcinoma featuring diffuse-type histopathology in Chinese population. Clin Cancer Res. 2005, 11: 6431-6441. 10.1158/1078-0432.CCR-05-0942.CrossRefPubMed
10.
go back to reference Ohyauchi M, Imatani A, Yonechi M, Asano N, Miura A, Iijima K, Koike T, Sekine H, Ohara S, Shimosegawa T: The polymorphism interleukin 8 -251 A/T influences the susceptibility of Helicobacter pylori related gastric diseases in the Japanese population. Gut. 2005, 54: 330-335. 10.1136/gut.2003.033050.CrossRefPubMedPubMedCentral Ohyauchi M, Imatani A, Yonechi M, Asano N, Miura A, Iijima K, Koike T, Sekine H, Ohara S, Shimosegawa T: The polymorphism interleukin 8 -251 A/T influences the susceptibility of Helicobacter pylori related gastric diseases in the Japanese population. Gut. 2005, 54: 330-335. 10.1136/gut.2003.033050.CrossRefPubMedPubMedCentral
11.
go back to reference Taguchi A, Ohmiya N, Shirai K, Mabuchi N, Itoh A, Hirooka Y, Niwa Y, Goto H: Interleukin-8 promoter polymorphism increases the risk of atrophic gastritis and gastric cancer in Japan. Cancer Epidemiol Biomarkers Prev. 2005, 14: 2487-2493. 10.1158/1055-9965.EPI-05-0326.CrossRefPubMed Taguchi A, Ohmiya N, Shirai K, Mabuchi N, Itoh A, Hirooka Y, Niwa Y, Goto H: Interleukin-8 promoter polymorphism increases the risk of atrophic gastritis and gastric cancer in Japan. Cancer Epidemiol Biomarkers Prev. 2005, 14: 2487-2493. 10.1158/1055-9965.EPI-05-0326.CrossRefPubMed
12.
go back to reference Flores-Orta D, Bosques-Padilla F, Gómez-Leija G, Frederick F: Comparative study of rapid urease test (Hazell test) vs CLO-test in the diagnosis of Helicobacter pylori infection. Gut. 1997, 41 (Suppl 3): A160-Published abstract, Flores-Orta D, Bosques-Padilla F, Gómez-Leija G, Frederick F: Comparative study of rapid urease test (Hazell test) vs CLO-test in the diagnosis of Helicobacter pylori infection. Gut. 1997, 41 (Suppl 3): A160-Published abstract,
13.
go back to reference Perez-Perez GI, Doworkin BM, Chodos JE, Blaser MJ: Campylobacter pylori antibodies in humans. Ann Intern Med. 1998, 109: 11-17.CrossRef Perez-Perez GI, Doworkin BM, Chodos JE, Blaser MJ: Campylobacter pylori antibodies in humans. Ann Intern Med. 1998, 109: 11-17.CrossRef
14.
go back to reference Hull J, Ackerman H, Isles K, Usen S, Pinder M, Thomson A, Kwiatkowski D: Unusual haplotypic structure of IL8, a susceptibility locus for a common respiratory virus. Am J Hum Genet. 2001, 69: 413-419. 10.1086/321291.CrossRefPubMedPubMedCentral Hull J, Ackerman H, Isles K, Usen S, Pinder M, Thomson A, Kwiatkowski D: Unusual haplotypic structure of IL8, a susceptibility locus for a common respiratory virus. Am J Hum Genet. 2001, 69: 413-419. 10.1086/321291.CrossRefPubMedPubMedCentral
15.
go back to reference Lorenz E, Frees KL, Schwartz DA: Determination of the TLR4 genotype using allele-specific PCR. Biotechniques. 2001, 31: 22-24.PubMed Lorenz E, Frees KL, Schwartz DA: Determination of the TLR4 genotype using allele-specific PCR. Biotechniques. 2001, 31: 22-24.PubMed
16.
go back to reference Bosques-Padilla FJ, Tijerina-Menchaca R, Perez-Perez GI, Flores Gutiérrez JP, Garza-González E: Comparison of Helicobacter pylori prevalence in swymptomatic patients in Northeastern Mexico with the rest of the country. Its association with gastrointestinal disease. Arch Med Res. 2003, 34: 60-63. 10.1016/S0188-4409(02)00459-9.CrossRefPubMed Bosques-Padilla FJ, Tijerina-Menchaca R, Perez-Perez GI, Flores Gutiérrez JP, Garza-González E: Comparison of Helicobacter pylori prevalence in swymptomatic patients in Northeastern Mexico with the rest of the country. Its association with gastrointestinal disease. Arch Med Res. 2003, 34: 60-63. 10.1016/S0188-4409(02)00459-9.CrossRefPubMed
17.
go back to reference Faber J, Meyer CU, Gemmer C, Russo A, Finn A, Murdoch C, Zenz W, Mannhalter C, Zabel BU, Schmitt HJ, Habermehl P, Zepp F, Knuf M: Human toll-like receptor 4 mutations are associated with susceptibility to invasive meningococcal disease in infancy. Pediatr Infect Dis J. 2006, 25: 80-81. 10.1097/01.inf.0000195595.22547.fe.CrossRefPubMed Faber J, Meyer CU, Gemmer C, Russo A, Finn A, Murdoch C, Zenz W, Mannhalter C, Zabel BU, Schmitt HJ, Habermehl P, Zepp F, Knuf M: Human toll-like receptor 4 mutations are associated with susceptibility to invasive meningococcal disease in infancy. Pediatr Infect Dis J. 2006, 25: 80-81. 10.1097/01.inf.0000195595.22547.fe.CrossRefPubMed
18.
go back to reference Child NJ, Yang IA, Pulletz MC, de Courcy-Golder K, Andrews AL, Pappachan VJ, Holloway JW: Polymorphisms in Toll-like receptor 4 and the systemic inflammatory response syndrome. Biochem Soc Trans. 2003, 31: 652-653. 10.1042/BST0310652.CrossRefPubMed Child NJ, Yang IA, Pulletz MC, de Courcy-Golder K, Andrews AL, Pappachan VJ, Holloway JW: Polymorphisms in Toll-like receptor 4 and the systemic inflammatory response syndrome. Biochem Soc Trans. 2003, 31: 652-653. 10.1042/BST0310652.CrossRefPubMed
19.
go back to reference Agnese DM, Calvano JE, Hahm SJ, Coyle SM, Corbett SA, Calvano SE, Lowry SF: Human toll-like receptor 4 mutations but not CD14 polymorphisms are associated with an increased risk of gram-negative infections. J Infect Dis. 2002, 186: 1522-1525. 10.1086/344893.CrossRefPubMed Agnese DM, Calvano JE, Hahm SJ, Coyle SM, Corbett SA, Calvano SE, Lowry SF: Human toll-like receptor 4 mutations but not CD14 polymorphisms are associated with an increased risk of gram-negative infections. J Infect Dis. 2002, 186: 1522-1525. 10.1086/344893.CrossRefPubMed
20.
go back to reference Lorenz E, Mira JP, Frees KL, Schwartz DA: Relevance of mutations in the TLR4 receptor in patients with gram-negative septic shock. Arch Intern Med. 2002, 162: 1028-1032. 10.1001/archinte.162.9.1028.CrossRefPubMed Lorenz E, Mira JP, Frees KL, Schwartz DA: Relevance of mutations in the TLR4 receptor in patients with gram-negative septic shock. Arch Intern Med. 2002, 162: 1028-1032. 10.1001/archinte.162.9.1028.CrossRefPubMed
21.
go back to reference Lamb R, Zeggini E, Thomson W, Donn R: Toll-like receptor 4 gene polymorphisms and susceptibility to juvenile idiopathic arthritis. Ann Rheum Dis. 2005, 64: 767-769. 10.1136/ard.2004.026930.CrossRefPubMed Lamb R, Zeggini E, Thomson W, Donn R: Toll-like receptor 4 gene polymorphisms and susceptibility to juvenile idiopathic arthritis. Ann Rheum Dis. 2005, 64: 767-769. 10.1136/ard.2004.026930.CrossRefPubMed
22.
go back to reference Lorenz E, Hallman M, Marttila R, Haataja R, Schwartz DA: Association between the Asp299Gly polymorphisms in the Toll-like receptor 4 and premature births in the Finnish population. Pediatr Res. 2002, 52: 373-376.CrossRefPubMed Lorenz E, Hallman M, Marttila R, Haataja R, Schwartz DA: Association between the Asp299Gly polymorphisms in the Toll-like receptor 4 and premature births in the Finnish population. Pediatr Res. 2002, 52: 373-376.CrossRefPubMed
Metadata
Title
Assessment of the toll-like receptor 4 Asp299Gly, Thr399Ile and interleukin-8 -251 polymorphisms in the risk for the development of distal gastric cancer
Authors
Elvira Garza-Gonzalez
Francisco J Bosques-Padilla
Sandra I Mendoza-Ibarra
Juan P Flores-Gutierrez
Hector J Maldonado-Garza
Guillermo I Perez-Perez
Publication date
01-12-2007
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2007
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-7-70

Other articles of this Issue 1/2007

BMC Cancer 1/2007 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine