Chonnam Med J.  2010 Apr;46(1):32-37. 10.4068/cmj.2010.46.1.32.

A Polymorphism of the MMP-1, EGF, and IL-LB Gene Is Not Correlated with Gastric Carcinogenesis

Affiliations
  • 1Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea. p1052ccy@hanmail.net
  • 2Department of Molecular Medicine Science, Chonnam National University Graduate School, Gwangju, Korea.

Abstract

MMP-1, EGF, and IL-1B gene polymorphism can be associated with gastric carcinogenesis. However, no study has yet confirmed the definitive role of these gene polymorphisms in gastric cancer risk. The 194 gastric cancer patients, 94 gastric adenoma patients, and 182 controls were used in this study. The SNP of the MMP-1 promoter, EGF, and IL-1B-31 were analyzed by PCR-RFLP and sequencing. The genotype frequency was compared between cases and controls, and a univariate and multivariate analysis were performed to determine the significant risk factors associated with gastric adenoma and adenocarcinoma. The frequency of 1G/2G genotypes in the MMP-1 promoter was similar to those in controls (p=0.734). The frequency of A/G genotypes in the EGF was similar to those in controls (p=0.239). The frequency of C/T genotypes in the IL-1B-31 was similar to those in controls (p=0.239). According to univariate analysis, male sex (p<0.0001), old age (> or =60, p<0.0001), atrophy (pepsinogen I/II < or =3, p<0.0001), and G/G genotype of EGF (p=0.034) were significant risk factors associated with gastric adenoma and carcinoma. However, male sex (p=0.002), old age (p<0.0001), and atrophy (p<0.0001) were the only significant risk factors associated with gastric adenoma and carcinoma according to the multivariate analysis. In conclusion, the SNP of the MMP-1 promoter, EGF, and IL-1B-31 did not correlate with the risk of gastric adenoma and adenocarcinoma. Sex, age, and atrophy were the significant risk factors of gastric cancer.

Keyword

Stomach neoplasms; Matrix metalloproteinase 1; Interleukin-1beta

MeSH Terms

Adenocarcinoma
Adenoma
Atrophy
Epidermal Growth Factor
Genotype
Humans
Interleukin-1beta
Male
Matrix Metalloproteinase 1
Multivariate Analysis
Risk Factors
Stomach Neoplasms
Epidermal Growth Factor
Interleukin-1beta
Matrix Metalloproteinase 1

Reference

1. Crew KD, Neugut AI. Epidemiology of gastric cancer. World J Gastroenterol. 2006. 12:354–362.
Article
2. Ushijima T, Sasako M. Focus on gastric cancer. Cancer Cell. 2004. 5:121–125.
Article
3. Dunbier A, Guilford P. Hereditary diffuse gastric cancer. Adv Cancer Res. 2001. 83:55–65.
Article
4. Correa P. Human gastric carcinogenesis: a multistep and multipfactorial process -First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. Cancer Res. 1992. 52:6735–6740.
5. Tahara E. Molecular mechanism of stomach carcinogenesis. J Cancer Res Clin Oncol. 1993. 119:265–272.
Article
6. Stadtlander CT, Waterbor JW. Molecular epidemiology, pathogenesis and prevention of gastric cancer. Carcinogenesis. 1999. 20:2195–2208.
Article
7. Neugut AI, Hayek M, Howe G. Epidemiology of gastric cancer. Semin Oncol. 1996. 23:281–291.
8. Kelly JR, Duggan JM. Gastric cancer epidemiology and risk factors. J Clin Epidemiol. 2003. 56:1–9.
Article
9. Malaty HM, Engstrand L, Pedersen NL, Graham DY. Helicobacter pylori infection: genetic and environmental influences. A study of twins. Ann Intern Med. 1994. 120:982–986.
Article
10. Yasui W, Yokozaki H, Fujimoto J, Naka K, Kuniyasu H, Tahara E. Genetic and epigenetic alterations in multistep carcinogenesis of the stomach. J Gastroenterol. 2000. 35:111–115.
11. Werner M, Becker KF, Keller G, Höfler H. Gastric adenocarcinoma: pathomorphology and molecular pathology. J Cancer Res Clin Oncol. 2001. 127:207–216.
Article
12. González CA, Sala N, Capellá G. Genetic susceptibility and gastric cancer risk. Int J Cancer. 2002. 100:249–260.
Article
13. Jorissen RN, Walker F, Pouliot N, Garrett TP, Ward CW, Burgess AW. Epidermal growth factor receptor: mechanisms of activation and signaling. Exp Cell Res. 2003. 284:31–53.
Article
14. Olayioye MA, Neve RM, Lane HA, Hynes NE. The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J. 2000. 19:3159–3167.
Article
15. Laurence DJ, Gusterson BA. The epidermal growth factor. A review of structural and functional relationships in the normal organism and in cancer cells. Tumour Biol. 1990. 11:229–261.
16. Singletary SE, Baker FL, Spitzer G, Tucker SL, Tomasovic B, Brock WA, et al. Biological effect of epidermal growth factor on the in vitro growth of human tumors. Cancer Res. 1987. 47:403–406.
17. Hamai Y, Matsumura S, Matsusaki K, Kitadai Y, Yoshida K, Yamaguchi Y, et al. A single nucleotide polymorphism in the 5' untranslated region of the EGF gene is associated with occurrence and malignant progression of gastric cancer. Pathobiology. 2005. 72:133–138.
Article
18. Kohn EC, Liotta LA. Molecular insights into cancer invasion: strategies for prevention and intervention. Cancer Res. 1995. 55:1856–1862.
19. Krueger S, Hundertmark T, Kalinski T, Peitz U, Wex T, Malfertheiner P, et al. Helicobacter pylori encoding the pathogenicity island activates matrix metalloproteinase 1 in gastric epithelial cells via JNK and ERK. J Biol Chem. 2006. 281:2868–2875.
Article
20. Ghilardi G, Biondi ML, Mangoni J, Leviti S, DeMonti M, Guarnelline E, et al. Matrix metalloproteinase-1 promotor polymorphism 1G/2G is correlated with colorectal cancer invasiveness. Clin Cancer Res. 2001. 7:2344–2346.
21. Hamajima N, Matuso K, Saito T, Tajima K, Okuma K, Yamao K, et al. Interleukin 1 polymorphisms, lifestyle factors, and Helicobacter pylori infection. Jpn J Cancer Res. 2001. 92:383–389.
Article
22. Chang YW, Jang JY, Kim NH, Lee JW, Lee HJ, Jung WW, et al. Interleukin-1B (IL-1B) polymorphisms and gastric mucosal levels of IL-1Beta cytokine in Korean patients with gastric cancer. Int J Cancer. 2005. 114:465–471.
Article
23. Watabe H, Mitsushima T, Yamaji Y, Okamoto M, Wata R, Kokubo T, et al. Predicting the development of gastric cancer from combining Helicobacter pylori antibodies and serum pepsinogen status: a prospective endoscopic cohort study. GUT. 2005. 54:764–768.
Article
24. Palli D, Saieva C, Luzzi I, Masala G, Topa S, Sera F, et al. Interleukin-1 Gene polymorphisms and gastric cancer risk in a high-risk Italian population. Am J Gastroenterol. 2005. 100:1941–1948.
Article
25. Peleteiro B, Lunet N, Carrilho C, Durães C, Machado JC, La Vecchia C, et al. Association between cytokine gene polymorphisms and gastric precancerous lesions: systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev. 2010. 19:762–776.
Article
Full Text Links
  • CMJ
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr