Abstract
Background
A G/C polymorphism in miRNA-146a (rs2910164) was shown to be associated with the risk of hepatocellular carcinoma.
Objective
This study aimed to examine the associations of the miR-146a G/C (rs2910164) and TLR4 +3725 G/C (rs11536889) polymorphisms with the risk of Helicobacter pylori (H. pylori) infection, gastric atrophy, and gastric cancer in a Japanese population.
Methods
Subjects for this study were 583 histologically diagnosed gastric cancer patients and age- and sex-frequency-matched 1,742 control outpatients (1,637 subjects were eligible for the analyses), who visited Aichi Cancer Center Hospital from the year 2001 to 2005. Serum pepsinogens were measured to evaluate gastric atrophy.
Results
When H. pylori-seropositive subjects or subjects with gastric atrophy were defined as H. pylori-infected subjects, the age- and sex-adjusted odds ratio (aOR) of severe gastric atrophy among the H. pylori infected was 1.44 (95% confidence interval [95% CI] = 0.89–2.34, p = 0.133) in G/G genotype of miR-146a polymorphism. When combined with TLR4 G/C polymorphism, the OR in those with miR-146a G/G and TLR4 G/C+C/C genotypes was significantly increased relative to those with miR-146a C/C+G/C and TLR4 G/G among the H. pylori-infected subjects: aOR = 2.04 (95% CI = 1.10–3.82, p = 0.025).
Conclusions
This study revealed the combined effect of miR-146a rs2910164 G/G and TLR4 +3725 C allele on the increased risk of severe gastric atrophy among the H. pylori-infected Japanese subjects.
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References
Parkin DM, Whelan SL, Ferlay J, Raymond L, Young J. Cancer incidence in five continents, vol. VII. Lyon: IARC Scientific Publications; 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 S, Aaltonen L, eds. Pathology and genetics. Tumours of the digestive system. WHO Classification of Tumours. Lyon: IARC Press; 2000.
Tsuji S, Tsujii M, Murata H, et al. Helicobacter pylori eradication to prevent gastric cancer: underlying molecular and cellular mechanisms. World J Gastroenterol. 2006;12:1671–1680.
Danesh J. Helicobacter pylori infection and gastric cancer: systematic review of the epidemiological studies. Aliment Pharmacol Ther. 1999;13:851–856.
Eslick GD, Lim LL, Byles JE, Xia HH, Talley NJ. Association of Helicobacter pylori infection with gastric carcinoma: a meta-analysis. Am J Gastroenterol. 1999;94:2373–2379.
Uemura N, Okamoto S, Yamamoto S, et al. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med. 2001;345:784–789.
Wong BC, Lam SK, Wong WM, et al. Helicobacter pylori eradication to prevent gastric cancer in a high-risk region of China: a randomized controlled trial. JAMA. 2004;291:187–194.
Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006;124:783–801.
Leulier F, Lemaitre B. Toll-like receptors—taking an evolutionary approach. Nat Rev Genet. 2008;9:165–178.
Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol. 2004;4:499–511.
Ambros V. The functions of animal microRNAs. Nature. 2004;431:350–355.
Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–297.
Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementary to lin-14. Cell. 1993;75:843–854.
Chen JF, Mandel EM, Thomson JM, et al. The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet. 2006;38:228–233.
Brennecke J, Hipfner DR, Stark A, Russell RB, Cohen SM. Bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell. 2003;113:25–36.
Cimmino A, Calin GA, Fabbri M, et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA. 2005;102:13944–13949.
Xu T, Zhu Y, Wei QK, et al. A functional polymorphism in the miR-146a gene is associated with the risk for hepatocellular carcinoma. Carcinogenesis. 2008;29:2126–2131.
Hamajima N, Naito M, Kondo T, Goto Y. Genetic factors involved in the development of Helicobacter pylori-related gastric cancer. Cancer Sci. 2006;97:1129–1138.
Hishida A, Matsuo K, Goto Y, et al. Toll-like receptor 4 +3725 G/C polymorphism, Helicobacter pylori seropositivity, and the risk of gastric atrophy and gastric cancer in Japanese. Helicobacter. 2009;14:47–53. Corrigendum in Helicobacter. 2009; 14:151–152.
Jazdzeski K, Murray EL, Franssila K, Jarzab B, Schoenberg DR, de la Chapelle A. Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma. Proc Natl Acad Sci USA. 2008;105:7269–7274.
Jazdzeski K, Liyanarachchi S, Swierniak M, et al. Polymorphic mature microRNAs from passenger strand of pre-miR-146a contribute to thyroid cancer. Proc Natl Acad Sci USA. 2009;106:1502–1505.
Xu B, Feng NH, Li PC, et al. A functional polymorphism in Pre-miR-146a gene is associated with prostate cancer risk and mature miR-146a expression in vivo. Prostate. 2010;70:467–472.
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.
Hamajima N, Saito T, Matsuo K, et al. Polymerase chain reaction with confronting two-pair primers for polymorphism genotyping. Jpn J Cancer Res. 2000;91:865–868.
Taganov KD, Boldin MP, Chang KJ, Baltimore D. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci USA. 2006;103:12481–12486.
Kimman TG, Banus S, Reijmerink N, et al. Association of interacting genes in the toll-like receptor signaling pathway, the antibody response to pertussis vaccination. PLoS One. 2008;3:e3665.
Rehmsmeier M, Steffen P, Hochsmann M, Giegerich R. Fast and effective prediction of microRNA/target duplexes. RNA. 2004;10:1507–1517.
International HapMap Project http://hapmap.ncbi.nlm.nih.gov/.
Miki K, Ichinose M, Shimizu A, 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.
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, Japan Public Health Center Study Group, 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.
Kuroda S, Morita S. A case of pernicious anemia with type A gastritis in an extremely elderly patient with dementia and heart failure. Nippon Ronen Igakkai Zasshi. 2008;45:335–337.
Acknowledgments
The authors wish to thank Ms. Yoko Mitsuda and all the staff involved in this study. This study was supported in part by a Grant-in-Aid for Scientific Research on Special Priority Areas of Cancer from the Japanese Ministry of Education, Culture, Sports, Science and Technology.
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Hishida, A., Matsuo, K., Goto, Y. et al. Combined Effect of miR-146a rs2910164 G/C Polymorphism and Toll-like Receptor 4 +3725 G/C Polymorphism on the Risk of Severe Gastric Atrophy in Japanese. Dig Dis Sci 56, 1131–1137 (2011). https://doi.org/10.1007/s10620-010-1376-1
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DOI: https://doi.org/10.1007/s10620-010-1376-1