中国汉族人群单核苷酸多态性与幽门螺杆菌相关性胃癌的关系研究
|
摘要
目的:探讨中国汉族人群基因单核苷酸多态性与H.pylori感染引起胃癌发生的关联性。
方法:采用病例对照研究的方法,收集了296例胃癌患者(病例组)和160例胃炎患者(对照组)。采用酶联免疫吸附实验检测血清中的抗H.pylori IgG抗体来确定受试者的H.pylori感染情况。使用Sequenom MassArray系统对PTPN11、NOD1、NOD2、CD14、TLR4、TLR9基因的TagSNPs进行基因分型。采用PCR-RFLP的方法,对中国汉族的268例胃癌(病例组)、190例慢性胃炎(对照组)患者的P53Arg72Pro和MDM2 SNP T309G的基因多态性位点进行了基因分型。
结果:中国汉族人群单核苷酸多态性与胃癌发生的相关性
1. P53 Arg72Pro和MDM2 SNPT309G与胃癌发生风险不具有相关性。
2. PTPN11基因第3内含子rs2301756位点SNP与胃癌的发病风险无关联性,该位点的多态性与H. pylori感染阳性胃癌的发生风险无相关性。
3.NOD1和NOD2基因多态性与胃癌发生的相关性
3.1. NOD1 rs2907749 GG基因型能降低胃癌的发生风险(调整后的OR0.50; 95% CI 0.26-0.95)而rs7789045 TT基因型能增加胃癌的风险(OR 2.14; 95%CI 1.20-3.82)。
3.2在H.pylori感染阳性的人群中,NOD1 rs7789045 TT能增加胃癌的发生风险(OR 2.05; 95%CI 1.07-3.94),并且NOD2 rs7205423 GC基因型(调整后OR 2.52; 95%CI 1.05-6.04)也能增加胃癌的发生风险。
3.3单体型分析显示,NOD1基因的AGT单体型(由顺序排列的rs2907749, rs2075820和rs7789045构成)在病例组和对照组中的分布有显著性的差别(校正后P: 0.04)。
4.TLR4基因多态性与胃癌发生的相关性
TLR4的rs2149356等位基因多态性位点的杂合子基因型显著性的增加了胃癌的发生风险(经过调整后OR,1.55; 95%CI, 1.02-2.36; P= 0.042)。rs7873784位点的隐性模型(CCvs. CG+GG)也显著性的增加了胃癌的发生风险(经过调整后OR分别为: OR,1.85; 95%CI, 1.01-3.37; P= 0.046和OR, 1.88; 95%CI, 1.03-3.43; P= 0.039)。
5.CD14基因多态性与胃癌发生的相关性
5.1 CD14的rs2569190 GA显性模型( GG+GA vs. AA)显著性降低了胃癌的发生风险(调整后分别为OR,0.64; 95%CI, 0.42-0.98 P=0.041;OR,0.64; 95%CI, 0.43-0.96 P=0.032)。
5.2 CD14基因的rs2563298,rs2569190,rs5744441构成3个单体型(CAC、CGT、AGC)。最常见的单体型是CAC,其在病例组和对照组人群有显著性的分布差异(P=0.048)。
结论:中国汉族人群P53 Arg 72Pro、MDM2 SNPT309G、PTPN11基因第3内含子rs2301756位点SNP不能影响胃癌的发病风险,这些位点的多态性与H. pylori感染阳性胃癌的发生风险无相关性。NOD1、NOD2、TLR4、CD14基因多态性可能与H.pylori相互作用,并且在中国汉族人群胃癌的发生中起着重要的作用。
Background:This study examined single nucleotide polymorphisms and their associations with the risk of developing gastric cancer in relation to Helicobacter pylori infection in Chinese han population.
Methods:We conducted a hospital-based case–control study including 296 incident gastric cancer patients and 160 gastritis controls. TagSNPs in PTPN11,NOD1,NOD2,CD14,TLR4,TLR9 genes were genotyped by using Sequenom MassArray system. Serum levels of anti-H.pylori IgG were measured by enzyme-linked immunosorbent assay to indicate H.pylori infection. PCR-RFLP was also applied in genotyping P53Arg72Pro and MDM2 SNP T309G in 268 patients with gastric cancer , and 190 gender-age-matched chronic gastritis patients served as controls.
Results:
1. P53 Arg 72Pro and MDM2 SNPT309G are not associated the risk of gastric cancer.
2. PTPN11 G/A polymorphism at intron 3 could not infect the risk of gastric cancer. PTPN11 polymorphism was not associated with H.Pylori infection states in both cancer patients and controls.
3. The association of NOD1 and NOD2 polymorphisms and gastric cancer
3.1 NOD1 rs2907749 GG genotype gene showed a decreased risk for gastric cancer [adjusted odds ratio (OR) 0.50; 95% confidence interval (CI) 0.26-0.95] while rs7789045 TT genotype showed an increased risk for gastric cancer (OR 2.14; 95%CI 1.20-3.82).
3.2 An elevated risk of gastric cancer was observed in subjects with H.pylori infection and NOD1 rs7789045 TT genotype (OR 2.05; 95%CI 1.07-3.94) or NOD2 rs7205423 GC genotype (OR 2.52; 95%CI 1.05-6.04).
3.3 Haplotype analysis suggested that the distribution of AGT (indicated as in the order of rs2907749, rs2075820 and rs7789045) in NOD1 between cases and control groups was significantly different (Pcorrected: 0.04).
4. the association of TLR4 polymorphisms and gastric cancer
TLR4 rs2149356 AC heterozygote genotype showed an elevated risk for gastric cancer (adjusted OR,1.55; 95%CI, 1.02-2.36; P= 0.042).An elevated risk for gastric cancer also was observed in subjects with rs7873784 CG heterozygote genotype and the recessive model (genotype CCvs. CG+GG) (adjusted OR,1.85; 95%CI, 1.01-3.37; P= 0.046 and OR, 1.88; 95%CI, 1.03-3.43; P= 0.039,respectively).
5. the association of CD14 polymorphisms and gastric cancer
5.1 CD14 rs2569190 the dominant model (GG+GA vs. AA)significantly decreased the risk of gastric cancer (adjusted OR,0.64; 95%CI,0.42-0.98 P=0.041;OR,0.64; 95%CI, 0.43-0.96 P=0.032,respectively).
5.2 rs2563298,rs2569190,rs5744441 in CD14 constructed three haplotypes(CAC、CGT、AGC),The most common haplotype was CAC and the distribution was significantly different between cases and controls (P=0.048).
Conclusions: P53 Arg 72Pro,MDM2 SNPT309G and PTPN11 G/A polymorphism at intron 3 could not infect the risk of gastric cancer. PTPN11 polymorphism was not associated with H.Pylori infection states in both cancer patients and controls.Genetic polymorphisms in NOD1,NOD2,TLR4,CD14 may interaction with H.pylori infection and may play important roles in developing gastric cancer in the Chinese population.
方法:采用病例对照研究的方法,收集了296例胃癌患者(病例组)和160例胃炎患者(对照组)。采用酶联免疫吸附实验检测血清中的抗H.pylori IgG抗体来确定受试者的H.pylori感染情况。使用Sequenom MassArray系统对PTPN11、NOD1、NOD2、CD14、TLR4、TLR9基因的TagSNPs进行基因分型。采用PCR-RFLP的方法,对中国汉族的268例胃癌(病例组)、190例慢性胃炎(对照组)患者的P53Arg72Pro和MDM2 SNP T309G的基因多态性位点进行了基因分型。
结果:中国汉族人群单核苷酸多态性与胃癌发生的相关性
1. P53 Arg72Pro和MDM2 SNPT309G与胃癌发生风险不具有相关性。
2. PTPN11基因第3内含子rs2301756位点SNP与胃癌的发病风险无关联性,该位点的多态性与H. pylori感染阳性胃癌的发生风险无相关性。
3.NOD1和NOD2基因多态性与胃癌发生的相关性
3.1. NOD1 rs2907749 GG基因型能降低胃癌的发生风险(调整后的OR0.50; 95% CI 0.26-0.95)而rs7789045 TT基因型能增加胃癌的风险(OR 2.14; 95%CI 1.20-3.82)。
3.2在H.pylori感染阳性的人群中,NOD1 rs7789045 TT能增加胃癌的发生风险(OR 2.05; 95%CI 1.07-3.94),并且NOD2 rs7205423 GC基因型(调整后OR 2.52; 95%CI 1.05-6.04)也能增加胃癌的发生风险。
3.3单体型分析显示,NOD1基因的AGT单体型(由顺序排列的rs2907749, rs2075820和rs7789045构成)在病例组和对照组中的分布有显著性的差别(校正后P: 0.04)。
4.TLR4基因多态性与胃癌发生的相关性
TLR4的rs2149356等位基因多态性位点的杂合子基因型显著性的增加了胃癌的发生风险(经过调整后OR,1.55; 95%CI, 1.02-2.36; P= 0.042)。rs7873784位点的隐性模型(CCvs. CG+GG)也显著性的增加了胃癌的发生风险(经过调整后OR分别为: OR,1.85; 95%CI, 1.01-3.37; P= 0.046和OR, 1.88; 95%CI, 1.03-3.43; P= 0.039)。
5.CD14基因多态性与胃癌发生的相关性
5.1 CD14的rs2569190 GA显性模型( GG+GA vs. AA)显著性降低了胃癌的发生风险(调整后分别为OR,0.64; 95%CI, 0.42-0.98 P=0.041;OR,0.64; 95%CI, 0.43-0.96 P=0.032)。
5.2 CD14基因的rs2563298,rs2569190,rs5744441构成3个单体型(CAC、CGT、AGC)。最常见的单体型是CAC,其在病例组和对照组人群有显著性的分布差异(P=0.048)。
结论:中国汉族人群P53 Arg 72Pro、MDM2 SNPT309G、PTPN11基因第3内含子rs2301756位点SNP不能影响胃癌的发病风险,这些位点的多态性与H. pylori感染阳性胃癌的发生风险无相关性。NOD1、NOD2、TLR4、CD14基因多态性可能与H.pylori相互作用,并且在中国汉族人群胃癌的发生中起着重要的作用。
Background:This study examined single nucleotide polymorphisms and their associations with the risk of developing gastric cancer in relation to Helicobacter pylori infection in Chinese han population.
Methods:We conducted a hospital-based case–control study including 296 incident gastric cancer patients and 160 gastritis controls. TagSNPs in PTPN11,NOD1,NOD2,CD14,TLR4,TLR9 genes were genotyped by using Sequenom MassArray system. Serum levels of anti-H.pylori IgG were measured by enzyme-linked immunosorbent assay to indicate H.pylori infection. PCR-RFLP was also applied in genotyping P53Arg72Pro and MDM2 SNP T309G in 268 patients with gastric cancer , and 190 gender-age-matched chronic gastritis patients served as controls.
Results:
1. P53 Arg 72Pro and MDM2 SNPT309G are not associated the risk of gastric cancer.
2. PTPN11 G/A polymorphism at intron 3 could not infect the risk of gastric cancer. PTPN11 polymorphism was not associated with H.Pylori infection states in both cancer patients and controls.
3. The association of NOD1 and NOD2 polymorphisms and gastric cancer
3.1 NOD1 rs2907749 GG genotype gene showed a decreased risk for gastric cancer [adjusted odds ratio (OR) 0.50; 95% confidence interval (CI) 0.26-0.95] while rs7789045 TT genotype showed an increased risk for gastric cancer (OR 2.14; 95%CI 1.20-3.82).
3.2 An elevated risk of gastric cancer was observed in subjects with H.pylori infection and NOD1 rs7789045 TT genotype (OR 2.05; 95%CI 1.07-3.94) or NOD2 rs7205423 GC genotype (OR 2.52; 95%CI 1.05-6.04).
3.3 Haplotype analysis suggested that the distribution of AGT (indicated as in the order of rs2907749, rs2075820 and rs7789045) in NOD1 between cases and control groups was significantly different (Pcorrected: 0.04).
4. the association of TLR4 polymorphisms and gastric cancer
TLR4 rs2149356 AC heterozygote genotype showed an elevated risk for gastric cancer (adjusted OR,1.55; 95%CI, 1.02-2.36; P= 0.042).An elevated risk for gastric cancer also was observed in subjects with rs7873784 CG heterozygote genotype and the recessive model (genotype CCvs. CG+GG) (adjusted OR,1.85; 95%CI, 1.01-3.37; P= 0.046 and OR, 1.88; 95%CI, 1.03-3.43; P= 0.039,respectively).
5. the association of CD14 polymorphisms and gastric cancer
5.1 CD14 rs2569190 the dominant model (GG+GA vs. AA)significantly decreased the risk of gastric cancer (adjusted OR,0.64; 95%CI,0.42-0.98 P=0.041;OR,0.64; 95%CI, 0.43-0.96 P=0.032,respectively).
5.2 rs2563298,rs2569190,rs5744441 in CD14 constructed three haplotypes(CAC、CGT、AGC),The most common haplotype was CAC and the distribution was significantly different between cases and controls (P=0.048).
Conclusions: P53 Arg 72Pro,MDM2 SNPT309G and PTPN11 G/A polymorphism at intron 3 could not infect the risk of gastric cancer. PTPN11 polymorphism was not associated with H.Pylori infection states in both cancer patients and controls.Genetic polymorphisms in NOD1,NOD2,TLR4,CD14 may interaction with H.pylori infection and may play important roles in developing gastric cancer in the Chinese population.
引文
[1] Rudi J, Kuck D, Rudy A,et al. Helicobacter pylori vacA genotypes and cagA gene in a series of 383 H. pylori-positive patients.[J]. Z Gastroentero, 2000, l 38(7):559–564.
[2] Hui W C, Daniel N, Serena C,et al.Effect of MDM2 SNP309 and p53 codon 72 polymorphisms on lung cancer risk and survival among non-smoking Chinese women in Singapore.[J].BMC Cancer 2010, http://www.biomedcentral.com/1471-2407/10/88
[3] Marjanka K. Schmidt,Scarlett R,et al Do MDM2 SNP309 and TP53 R72P Interact in Breast Cancer Susceptibility? A Large Pooled Series from the Breast Cancer Association Consortium. [J].Cancer Res,2007; 67(19): 9584-9590
[4] Bente A. T,Cliff M, Janina S,et al.MDM2 SNP309 T>G alone or in combination with the TP53 R72P polymorphism does not appear to in?uence disease expression and age of diagnosis of colorectal cancer in HNPCC patients. [J]. Int. J. Cancer,2006: 120(3):563–565
[5] [5]Ming Y, Yongli G, Xuemei Z,et al Interaction of P53 Arg72Pro and MDM2 T309G polymorphisms and their associations with risk of gastric cardia cancer. [J]. Carcinogenesis,2007;28(9) 1996–2001
[6] Gordon C ,Demetrios K,Benjamin G. N. The tyrosine phosphatase Shp2 (PTPN11) in cancer[J]. Cancer Metastasis Rev ,2008,27:179–192
[7] Hatakeyama M. The role of Helicobacter pylori CagA in gastric carcinogenesis[J]. Int J Hematol. 2006;84(4):301-8.
[8] Asahi H, Keitaro M, Yasuyuki G,et al.Associations of a PTPN11 G/A polymorphism at intron 3 with Helicobactor pylori seropositivity, gastric atrophyand gastric cancer in Japanese[J]. BMC Gastroenterol. 2009 9;9:51. http://www.biomedcentral.com/1471-230x/9/51
[9] Yasuyuki G, Takafumi A, Kazuhito Y,et al. Association between serum pepsinogens and polymorphism of encoding SHP-2 among seropositive Japanese[J]. Int. J. Cancer,2006 ,118, 203–208
[10] Fukata M, Abreu MT. Role of toll-like receptors in gastrointestinal malignancies. [J] .Oncogene, 2008, 27 (2):234-250.
[11] Haziot A, Chen S, Ferrero E,et al. The monocyte differentiation antigen, CD14, is anchored to the cell membrane by aphosphatidylinositol linkage. [J].J Immunol 1988;141:547-52.
[12] AriasMA, Rey Nores JE,Vita N, et al. Cutting edge:human B cell function is regulated by interaction with soluble CD14: opposite effects on IgG1and IgE production. [J]. J Immunol 2000;164:3480-6.
[13] Girardin SE, Tournebize R, Mavris M,et al. CARD4/Nod1 mediates NF-kappaB and JNK activation by invasive Shigella flexneri. EMBO Rep 2001; 2:736-42.
[14] Strober W, Murray PJ, Kitani AWatanabe T. Signalling pathways and molecular interactions of NOD1 and NOD2. [J]. Nat Rev Immunol 2006; 6:9-20.
[15] Hofner P, Gyulai Z, Kiss ZF,et al. Genetic polymorphisms of NOD1 and IL-8, but not polymorphisms of TLR4 genes, are associated with Helicobacter pylori-induced duodenal ulcer and gastritis. [J].Helicobacter 2007; 12:124-31.
[16] Kara B, Akkiz H, Doran F,et al. The significance of E266K polymorphism in the NOD1 gene on Helicobacter pylori infection: an effective force on pathogenesis? [J].Clin Exp Med 2010; 10:107-12.
[17] Angeletti S, Galluzzo S, Santini D, et al.NOD2/CARD15 polymorphisms impair innate immunity and increase susceptibility to gastric cancer in an Italian population. [J]. Hum Immunol 2009; 70:729-32.
[18] Rosenstiel P, Hellmig S, Hampe J,et al. Influence of polymorphisms in the NOD1/CARD4 and NOD2/CARD15 genes on the clinical outcome of Helicobacter pylori infection. [J]. Cell Microbiol 2006; 8:1188-98.
[19] Yazdanyar S, Nordestgaard BG. NOD2/CARD15 genotype and common gastrointestinal diseases in 43,600 individuals. [J]. J Intern Med 2010; 267:228-36.
[1] Dumont P, Leu JL, Della Pietra AC III,et al. The codon 72 polymorphic variants of p53 have markedly diverent apoptosis potential. [J].Nat Genet,2003, 33(3):357–365
[2] Bergamaschi D, Gasco M, Hiller L,et al. p53 polymorphism in?uences response in cancer chemotherapy via modulation of p73-dependent apoptosis. [J].Cancer Cell 2003;3(4): 387–402.
[3] ThomasM, Kalita A, Labrecque S, et al.Two polymorphic variants of wild-type p53 differ biochemically and biologically. [J]. Mol Cell Biol. 1999(2);19:1092–1100.
[4] Yong Zhou, Ni Li, Wen Zhuang,et al.P53 codon 72 polymorphism and gastric cancer: a meta-analysis of the literature. [J]. Int J Cancer. 2007;121(7):1481-6.
[5] Lessileia Gomes de Souza,Jacqueline Miranda de Lima,Ismael Dale Cotrim,et al. P53 Arg72Pro Polymorphism in Gastric Cancer Patients. [J]. J Gastrointest Canc, 2009 40(1-2):41–45
[6] Jong Gwang Kim, Sang Kyun Sohn, Yee Soo Chae,et al Wansik Yu.TP53 codon 72 polymorphism associated with prognosis in patients with advanced gastric cancer treated with paclitaxel and cisplatin.[J].Cancer Chemother Pharmacol ;2009;64(2):355–360
[7] Toru H, Shinji T, Yasuhiko K,et al. p53 codon 72 polymorphism in gastric cancer susceptibility in patients with Helicobacter pylori-associated chronic gastritis. [J]. Int J Cancer.2002;100(3):304–308.
[8] D. Sz? oke, B. Moln′ar, N. Solymosi,et al. The RR genotype of codon 72 of p53 gene reduces the development of intestinal metaplasia. [J]. Digestive and Liver Disease 2009;41(3);179–184
[9] Nayoung Kim, Sung-Il Cho, Hye Seung Lee,et al. The Discrepancy Between Genetic Polymorphism of p53 codon 72 and the Expression of p53 Protein in Helicobacter pylori-Associated Gastric Cancer in Korea. [J]. Dig Dis Sci ;2010; 55(1):101–110
[10] ZUN-WU ZHANG,MD,PhD,PAUL NEWCOMB,et al. A Comparison Study of Gastric Cancer Risk in Patients with Duodenal and Gastric Ulcer Roles of Gastric Mucosal Histology and p53 Codon 72 Polymorphism; [J]. Digestive Diseases and Sciences,2004;49(2);254-259
[11] Zhao-Hui H, Dong H, Li-Hua L,et al. Prognostic role of p53 codon 72 polymorphism in gastric cancer patients treated with Xuorouracil-based adjuvant chemotherapy. [J]. J Cancer Res Clin Oncol ;2008 ;134(10):1129–1134
[12] Chen J, Wu X, Lin J, Levine AJ. mdm-2 inhibits the G1 arrest and apoptosis functions of the p53 tumor suppressor protein.[J].Mol Cell Biol ;1996;16(5):2445–52.
[13] Soussi T, Beroud C. Assessing TP53 status in human tumors to evaluate clinical outcome. [J].Nat Rev Cancer 2001;1(3):233–40.
[14] Poyurovsky MV, Prives C. Unleashing the power of p53: Lessons from mice and men. [J]. Genes Develop;2006; 20:125–131.
[15] Bond GL, Levine AJ.A single nucleotide polymorphismin the p53 pathway interacts with gender, environmental stresses and tumor genetics to in?uence cancer in humans. [J].Oncogene 2007;26: 1317–1323.
[16] HuW, Feng Z,Ma L,et al.A single nucleotide polymorphism in the MDM2 gene disrupts the oscillation of p53 and MDM2 levels in cells. [J].Cancer Res;2007 67(5): 2757–2765.
[17] Y. G. CHO, B. J. CHOI, J. H. SONG, et al.No association of MDM2 T309G polymorphism with susceptibility to Korean gastric cancer patients. [J]. Neoplasma;2008; 55(3)256-260.
[18] Daniele B, Yardena S, Alexandra S et al.preferentially binds p53 proline-rich region and modulates apoptotic function of codon 72-polymorphic p53. [J]. Nat. Genet.2006, 38(10), 1133–1141.
[1] Takafumi A,Yasuyuki G, Osamu M,et al. Causal role of Helicobacter pylori infection in gastric cancer .World J Gastroenterol. 2006 12(2):181-6.
[2] Asahi H, Keitaro M, Yasuyuki G, et al.Associations of a PTPN11 G/A polymorphism at intron 3 with Helicobactor pylori seropositivity, gastric atrophy and gastric cancer in Japanese[J]. BMC Gastroenterol. 2009 9;9:51. http://www.biomedcentral.com/1471-230x/9/51
[3] Yasuyuki G, Takafumi A, Kazuhito Y,et al. Association between serum pepsinogens and polymorphism of encoding SHP-2 among seropositive Japanese[J]. Int. J. Cancer,2006 ,118, 203–208
[4] Sayo K, Yasuyuki G, Lucy S. I,et al. Significant association between PTPN11 polymorphism and gastric atrophy among Japanese Brazilians[J]. Gastric Cancer ,2006),9: 277–283
[5] Nobuyuki H, Bakhodir R, Yusuf M et al. Associations between a PTPN11 Polymorphism and Gastric Atrophy - Opposite in Uzbekistan to that in Japan[J]. Asian Pac J Cancer Prev. 2008;9(2):217-20
[6] Tahara E. Molecular mechanism of stomach carcinogenesis.[J ]Cancer Res Clin Oncol. 1993;119:265–272.
[7] Correa P. Human gastric pathogenesis: a multistep and multifactorial process. First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention[J]. Cancer Res.1992;52:6735–40.
[8] Jin Soo K ,Ok R S, Hyung K K et al. Overexpression of Protein Phosphatase Non-receptor Type 11 (PTPN11) in Gastric Carcinomas. Dig Dis Sci ,2010, 55:1565–1569
[9] Kanada, R., Uchida, T., Tsukamoto, Y., et al. Genotyping of the cagA gene of Helicobacter pylori on immunohistochemistry with East Asian CagA-specific antibody[J]. Pathol Int ,2008,58, 218–225.
[1] Strober W, Murray PJ, Kitani AWatanabe T. Signalling pathways and molecular interactions of NOD1 and NOD2.[J]. Nat Rev Immunol 2006; 6:9-20.
[2] Clarke TB, Davis KM, Lysenko ES, Zhou AY,et al. Recognition of peptidoglycan from the microbiota by Nod1 enhances systemic innate immunity.[J]. Nat Med 2010; 16:228-31.
[3] Rosenstiel P, Hellmig S, Hampe J,et al. Influence of polymorphisms in the NOD1/CARD4 and NOD2/CARD15 genes on the clinical outcome of Helicobacter pylori infection. [J].Cell Microbiol 2006; 8:1188-98.
[4] Necchi V, Sommi P, Ricci VSolcia E. In vivo accumulation of Helicobacter pylori products, NOD1, ubiquitinated proteins and proteasome in a novel cytoplasmic structure.[J] PLoS One 2010; 5:e9716.
[5] Hofner P, Gyulai Z, Kiss ZF,et al. Genetic polymorphisms of NOD1 and IL-8, but not polymorphisms of TLR4 genes, are associated with Helicobacter pylori-induced duodenal ulcer and gastritis.[J]. Helicobacter 2007; 12:124-31.
[6] Kara B, Akkiz H, Doran F, Bayram S, et al. The significance of E266K polymorphism in the NOD1 gene on Helicobacter pylori infection: an effective force on pathogenesis? [J].Clin Exp Med 2010; 10:107-12.
[7] Zouali H, Lesage S, Merlin F,et al. CARD4/NOD1 is not involved in inflammatory bowel disease.[J].Gut 2003; 52:71-4.
[8] Gabriel SB, Schaffner SF, Nguyen H, et al. The structure of haplotype blocks in the human genome .[J]. Science 2002; 296:2225-9.
[9] D Franchimont , S Vermeire, H El Housni,et al. Deficient host-bacteria interactions in in?ammatory bowel disease? The toll-like receptor (TLR)-4 Asp299gly polymorphism is associated with Crohn’s disease and ulcerative colitis.[J]. Gut 2004;53(7):987–992.
[10] Lorenz E, Mira JP, Frees KL,et al.Relevance of mutations in the TLR4 receptor in patients with gram-negative septic shock.[J]. Arch Intern Med 2002;162(9):1028–1032.
[11] Kiechl S, Lorenz E, Reindl M,et al. Toll-like receptor 4 polymorphisms and atherogenesis.[J]. N Engl J Med 2002;347(3):185–192.
[1] El-Omar EM. The importance of interleukin 1beta in Helicobacter pylori associated disease.[J]. Gut 2001; 48(6): 743–7.
[2] Bidwell J, Keen L, Gallagher G, et al.Cytokine gene polymorphism in human disease: on-line databases, supplement 1. [J].Genes Immun,2001; 2(2): 61–70.
[3] Peek RM Jr,Blaser MJ. Helicobacter pylori and gastrointestinal tract adenocarcinomas.[J].Nat Rev Cancer.2002,2(1):28-37.
[4] Machado JC, Pharoah P, Sousa S, et al.Interleukin 1B and interleukin 1RN polymorphisms are associated with increased risk of gastric carcinoma.[J]. Gastroenterology ,2001; 121(4): 823–9.
[5] Figueiredo C, Machado JC, Pharoah P, et al.Helicobacter pylori and interleukin 1 genotyping: an opportunity to identify high-risk individuals for gastric carcinoma. [J].J Natl Cancer Inst 2002; 94: 1680–7.
[6] Zeng ZR, Hu PJ, Hu S, et al. association of interleukin 1B gene polymorphism and gastric cancer in high and low prevalence regions in China.[J]. Gut .2003,52(12):1684-1689
[7] Shuiping Tu, Govind Bhagat, Guanglin Cui, et al. Wang .Overexpression of interleukin-1[beta] induces gastric in?ammation and cancer and mobilizes myeloid-derived suppressor cells in mice.[J]. Cancer Cell ,2008; 14(5): 408–19.
[8] Shintaro Kamizono, Yuji Hiromatsu, Naoko Seki, et al.A polymorphism of the 5′?anking region of tumour necrosis factorαgene is associated with thyroid-associated ophthalmopathy in Japanese.[J]. Clin Endocrinol 2000; 52(6): 759–64.
[9] Yamaguchi E, Itoh A, Hizawa N, et al.The gene polymorphism of tumor necrosis factor-β, but not that of tumor necrosis factor-α, is associated with the prognosis of sarcoidosis.[J].Chest 2001; 119(3): 753–61.
[10] T. Higuchi, N. Seki, S. Kamizono, et al.Polymorphism of the 5′-?anking region of the human tumor necrosis factor (TNF)-αgene in Japanese.[J]. Tissue Antigens 1998; 51(6): 605–12.
[11] D’Alfonso S, Richiardi PM. A polymorphic variation in a putative regulation box of the TNFαpromoter region. [J].Immunogenet 1994; 39(2): 150–5.
[12] Emad M E,Charles S R, Marilie D G,et al. Increased risk of Noncardia gastric cancer asociated with proinflammatory cytokine gene Polymorphisms.[J]. Gastroenterology,2003,124(5);1193- 1201.
[13] Arbour NC, Lorenz E, Schutte BC, et al.TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. [J].Nat Genet 2000;25(2):187–191.
[14] D Franchimont , S Vermeire, H El Housni, et al.Deficient host-bacteria interactions in in?ammatory bowel disease? The toll-like receptor (TLR)-4 Asp299gly polymorphism is associated with Crohn’s disease and ulcerative colitis.[J]. Gut 2004;53(7):987–992.
[15] Lorenz E, Mira JP, Frees KL et al. Relevance of mutations in the TLR4 receptor in patients with gram-negative septic shock. [J].Arch Intern Med 2002;162(9):1028–1032.
[16] Kiechl S, Lorenz E, Reindl M, et al. Toll-like receptor 4 polymorphisms and atherogenesis.[J]. N Engl J Med 2002;347(3):185–192.
[17] Hold GL, Rabkin CS, Chow WH et al. A functional polymorphism of toll-likereceptor 4 gene increases risk of gastric carcinoma and its precursors.[J]. Gastroenterology 2007;132(3):905–912.
[18] Tahara T, Arisawa T, Wang FY, et al. Toll-like receptor 2–196 to 174del polymorphism influences the susceptibility of Japanese people to gastric cancer .[J].Cancer Sci, 2007, 98(11): 1790–1794.
[19] Ng MT, Van’t Hof R, Crockett JC, et al. Increase in NF-κB binding affinity of the C allelic variant of the Toll-like receptor 9 -1237T/C polymorphism is associated with Helicobacter pylori induced gastric disease.[J]. Infect Immun, 2010,78 (3):1345-52.
[20] Goto Y, Ando T, Yamamoto K, Tamakoshi A et al.Association between serum pepsinogens and polymorphism of PTPN11 encoding SHP-2 among H pylori seropositive Japanese. [J].Int J Cancer. 2006;118(1):203-8
[21] Hishida A, Matsuo K, Goto Y, et al.Associations of a PTPN11 G/A polymorphism at intron 3 with Helicobactor pylori seropositivity, gastric atrophy and gastric cancer in Japanese.[J].BMC Gastroenterology: 2009, 9:51 http://www.biomedcentral.com/1471-230X/9/51
[22] Toru HIYAMA1, Shinji TANAKA, et al.p53 Codon 72 polymorphism in gastric cancer susceptibility in patients with Helicobacter pylori-associated chronic gastritis.[J].Int. J. Cancer:2002, 100(3), 304–308
[23] Nayoung Kim, Sung-Il Cho, Hye Seung Lee, et al.The Discrepancy Between Genetic Polymorphism of p53 Codon 72 and the Expression of p53 Protein in Helicobacter pylori-Associated Gastric Cancer in Korea.[J].Dig Dis Sci :2010, 55(1):101–110
[24] Bond GL, Hu W, Bond EE, et al. A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans.[J].Cell 2004;119(5):591–602.
[25] Xiaoyong Wang, Jing Yang,Bo Ho, et al. Interaction of Helicobacter pylori with Genetic Variants in the MDM2 Promoter, is Associated with Gastric Cancer Susceptibility in Chinese Patients. [J].Helicobacter ;2009 ;14(5): 466–471
[2] Hui W C, Daniel N, Serena C,et al.Effect of MDM2 SNP309 and p53 codon 72 polymorphisms on lung cancer risk and survival among non-smoking Chinese women in Singapore.[J].BMC Cancer 2010, http://www.biomedcentral.com/1471-2407/10/88
[3] Marjanka K. Schmidt,Scarlett R,et al Do MDM2 SNP309 and TP53 R72P Interact in Breast Cancer Susceptibility? A Large Pooled Series from the Breast Cancer Association Consortium. [J].Cancer Res,2007; 67(19): 9584-9590
[4] Bente A. T,Cliff M, Janina S,et al.MDM2 SNP309 T>G alone or in combination with the TP53 R72P polymorphism does not appear to in?uence disease expression and age of diagnosis of colorectal cancer in HNPCC patients. [J]. Int. J. Cancer,2006: 120(3):563–565
[5] [5]Ming Y, Yongli G, Xuemei Z,et al Interaction of P53 Arg72Pro and MDM2 T309G polymorphisms and their associations with risk of gastric cardia cancer. [J]. Carcinogenesis,2007;28(9) 1996–2001
[6] Gordon C ,Demetrios K,Benjamin G. N. The tyrosine phosphatase Shp2 (PTPN11) in cancer[J]. Cancer Metastasis Rev ,2008,27:179–192
[7] Hatakeyama M. The role of Helicobacter pylori CagA in gastric carcinogenesis[J]. Int J Hematol. 2006;84(4):301-8.
[8] Asahi H, Keitaro M, Yasuyuki G,et al.Associations of a PTPN11 G/A polymorphism at intron 3 with Helicobactor pylori seropositivity, gastric atrophyand gastric cancer in Japanese[J]. BMC Gastroenterol. 2009 9;9:51. http://www.biomedcentral.com/1471-230x/9/51
[9] Yasuyuki G, Takafumi A, Kazuhito Y,et al. Association between serum pepsinogens and polymorphism of encoding SHP-2 among seropositive Japanese[J]. Int. J. Cancer,2006 ,118, 203–208
[10] Fukata M, Abreu MT. Role of toll-like receptors in gastrointestinal malignancies. [J] .Oncogene, 2008, 27 (2):234-250.
[11] Haziot A, Chen S, Ferrero E,et al. The monocyte differentiation antigen, CD14, is anchored to the cell membrane by aphosphatidylinositol linkage. [J].J Immunol 1988;141:547-52.
[12] AriasMA, Rey Nores JE,Vita N, et al. Cutting edge:human B cell function is regulated by interaction with soluble CD14: opposite effects on IgG1and IgE production. [J]. J Immunol 2000;164:3480-6.
[13] Girardin SE, Tournebize R, Mavris M,et al. CARD4/Nod1 mediates NF-kappaB and JNK activation by invasive Shigella flexneri. EMBO Rep 2001; 2:736-42.
[14] Strober W, Murray PJ, Kitani AWatanabe T. Signalling pathways and molecular interactions of NOD1 and NOD2. [J]. Nat Rev Immunol 2006; 6:9-20.
[15] Hofner P, Gyulai Z, Kiss ZF,et al. Genetic polymorphisms of NOD1 and IL-8, but not polymorphisms of TLR4 genes, are associated with Helicobacter pylori-induced duodenal ulcer and gastritis. [J].Helicobacter 2007; 12:124-31.
[16] Kara B, Akkiz H, Doran F,et al. The significance of E266K polymorphism in the NOD1 gene on Helicobacter pylori infection: an effective force on pathogenesis? [J].Clin Exp Med 2010; 10:107-12.
[17] Angeletti S, Galluzzo S, Santini D, et al.NOD2/CARD15 polymorphisms impair innate immunity and increase susceptibility to gastric cancer in an Italian population. [J]. Hum Immunol 2009; 70:729-32.
[18] Rosenstiel P, Hellmig S, Hampe J,et al. Influence of polymorphisms in the NOD1/CARD4 and NOD2/CARD15 genes on the clinical outcome of Helicobacter pylori infection. [J]. Cell Microbiol 2006; 8:1188-98.
[19] Yazdanyar S, Nordestgaard BG. NOD2/CARD15 genotype and common gastrointestinal diseases in 43,600 individuals. [J]. J Intern Med 2010; 267:228-36.
[1] Dumont P, Leu JL, Della Pietra AC III,et al. The codon 72 polymorphic variants of p53 have markedly diverent apoptosis potential. [J].Nat Genet,2003, 33(3):357–365
[2] Bergamaschi D, Gasco M, Hiller L,et al. p53 polymorphism in?uences response in cancer chemotherapy via modulation of p73-dependent apoptosis. [J].Cancer Cell 2003;3(4): 387–402.
[3] ThomasM, Kalita A, Labrecque S, et al.Two polymorphic variants of wild-type p53 differ biochemically and biologically. [J]. Mol Cell Biol. 1999(2);19:1092–1100.
[4] Yong Zhou, Ni Li, Wen Zhuang,et al.P53 codon 72 polymorphism and gastric cancer: a meta-analysis of the literature. [J]. Int J Cancer. 2007;121(7):1481-6.
[5] Lessileia Gomes de Souza,Jacqueline Miranda de Lima,Ismael Dale Cotrim,et al. P53 Arg72Pro Polymorphism in Gastric Cancer Patients. [J]. J Gastrointest Canc, 2009 40(1-2):41–45
[6] Jong Gwang Kim, Sang Kyun Sohn, Yee Soo Chae,et al Wansik Yu.TP53 codon 72 polymorphism associated with prognosis in patients with advanced gastric cancer treated with paclitaxel and cisplatin.[J].Cancer Chemother Pharmacol ;2009;64(2):355–360
[7] Toru H, Shinji T, Yasuhiko K,et al. p53 codon 72 polymorphism in gastric cancer susceptibility in patients with Helicobacter pylori-associated chronic gastritis. [J]. Int J Cancer.2002;100(3):304–308.
[8] D. Sz? oke, B. Moln′ar, N. Solymosi,et al. The RR genotype of codon 72 of p53 gene reduces the development of intestinal metaplasia. [J]. Digestive and Liver Disease 2009;41(3);179–184
[9] Nayoung Kim, Sung-Il Cho, Hye Seung Lee,et al. The Discrepancy Between Genetic Polymorphism of p53 codon 72 and the Expression of p53 Protein in Helicobacter pylori-Associated Gastric Cancer in Korea. [J]. Dig Dis Sci ;2010; 55(1):101–110
[10] ZUN-WU ZHANG,MD,PhD,PAUL NEWCOMB,et al. A Comparison Study of Gastric Cancer Risk in Patients with Duodenal and Gastric Ulcer Roles of Gastric Mucosal Histology and p53 Codon 72 Polymorphism; [J]. Digestive Diseases and Sciences,2004;49(2);254-259
[11] Zhao-Hui H, Dong H, Li-Hua L,et al. Prognostic role of p53 codon 72 polymorphism in gastric cancer patients treated with Xuorouracil-based adjuvant chemotherapy. [J]. J Cancer Res Clin Oncol ;2008 ;134(10):1129–1134
[12] Chen J, Wu X, Lin J, Levine AJ. mdm-2 inhibits the G1 arrest and apoptosis functions of the p53 tumor suppressor protein.[J].Mol Cell Biol ;1996;16(5):2445–52.
[13] Soussi T, Beroud C. Assessing TP53 status in human tumors to evaluate clinical outcome. [J].Nat Rev Cancer 2001;1(3):233–40.
[14] Poyurovsky MV, Prives C. Unleashing the power of p53: Lessons from mice and men. [J]. Genes Develop;2006; 20:125–131.
[15] Bond GL, Levine AJ.A single nucleotide polymorphismin the p53 pathway interacts with gender, environmental stresses and tumor genetics to in?uence cancer in humans. [J].Oncogene 2007;26: 1317–1323.
[16] HuW, Feng Z,Ma L,et al.A single nucleotide polymorphism in the MDM2 gene disrupts the oscillation of p53 and MDM2 levels in cells. [J].Cancer Res;2007 67(5): 2757–2765.
[17] Y. G. CHO, B. J. CHOI, J. H. SONG, et al.No association of MDM2 T309G polymorphism with susceptibility to Korean gastric cancer patients. [J]. Neoplasma;2008; 55(3)256-260.
[18] Daniele B, Yardena S, Alexandra S et al.preferentially binds p53 proline-rich region and modulates apoptotic function of codon 72-polymorphic p53. [J]. Nat. Genet.2006, 38(10), 1133–1141.
[1] Takafumi A,Yasuyuki G, Osamu M,et al. Causal role of Helicobacter pylori infection in gastric cancer .World J Gastroenterol. 2006 12(2):181-6.
[2] Asahi H, Keitaro M, Yasuyuki G, et al.Associations of a PTPN11 G/A polymorphism at intron 3 with Helicobactor pylori seropositivity, gastric atrophy and gastric cancer in Japanese[J]. BMC Gastroenterol. 2009 9;9:51. http://www.biomedcentral.com/1471-230x/9/51
[3] Yasuyuki G, Takafumi A, Kazuhito Y,et al. Association between serum pepsinogens and polymorphism of encoding SHP-2 among seropositive Japanese[J]. Int. J. Cancer,2006 ,118, 203–208
[4] Sayo K, Yasuyuki G, Lucy S. I,et al. Significant association between PTPN11 polymorphism and gastric atrophy among Japanese Brazilians[J]. Gastric Cancer ,2006),9: 277–283
[5] Nobuyuki H, Bakhodir R, Yusuf M et al. Associations between a PTPN11 Polymorphism and Gastric Atrophy - Opposite in Uzbekistan to that in Japan[J]. Asian Pac J Cancer Prev. 2008;9(2):217-20
[6] Tahara E. Molecular mechanism of stomach carcinogenesis.[J ]Cancer Res Clin Oncol. 1993;119:265–272.
[7] Correa P. Human gastric pathogenesis: a multistep and multifactorial process. First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention[J]. Cancer Res.1992;52:6735–40.
[8] Jin Soo K ,Ok R S, Hyung K K et al. Overexpression of Protein Phosphatase Non-receptor Type 11 (PTPN11) in Gastric Carcinomas. Dig Dis Sci ,2010, 55:1565–1569
[9] Kanada, R., Uchida, T., Tsukamoto, Y., et al. Genotyping of the cagA gene of Helicobacter pylori on immunohistochemistry with East Asian CagA-specific antibody[J]. Pathol Int ,2008,58, 218–225.
[1] Strober W, Murray PJ, Kitani AWatanabe T. Signalling pathways and molecular interactions of NOD1 and NOD2.[J]. Nat Rev Immunol 2006; 6:9-20.
[2] Clarke TB, Davis KM, Lysenko ES, Zhou AY,et al. Recognition of peptidoglycan from the microbiota by Nod1 enhances systemic innate immunity.[J]. Nat Med 2010; 16:228-31.
[3] Rosenstiel P, Hellmig S, Hampe J,et al. Influence of polymorphisms in the NOD1/CARD4 and NOD2/CARD15 genes on the clinical outcome of Helicobacter pylori infection. [J].Cell Microbiol 2006; 8:1188-98.
[4] Necchi V, Sommi P, Ricci VSolcia E. In vivo accumulation of Helicobacter pylori products, NOD1, ubiquitinated proteins and proteasome in a novel cytoplasmic structure.[J] PLoS One 2010; 5:e9716.
[5] Hofner P, Gyulai Z, Kiss ZF,et al. Genetic polymorphisms of NOD1 and IL-8, but not polymorphisms of TLR4 genes, are associated with Helicobacter pylori-induced duodenal ulcer and gastritis.[J]. Helicobacter 2007; 12:124-31.
[6] Kara B, Akkiz H, Doran F, Bayram S, et al. The significance of E266K polymorphism in the NOD1 gene on Helicobacter pylori infection: an effective force on pathogenesis? [J].Clin Exp Med 2010; 10:107-12.
[7] Zouali H, Lesage S, Merlin F,et al. CARD4/NOD1 is not involved in inflammatory bowel disease.[J].Gut 2003; 52:71-4.
[8] Gabriel SB, Schaffner SF, Nguyen H, et al. The structure of haplotype blocks in the human genome .[J]. Science 2002; 296:2225-9.
[9] D Franchimont , S Vermeire, H El Housni,et al. Deficient host-bacteria interactions in in?ammatory bowel disease? The toll-like receptor (TLR)-4 Asp299gly polymorphism is associated with Crohn’s disease and ulcerative colitis.[J]. Gut 2004;53(7):987–992.
[10] Lorenz E, Mira JP, Frees KL,et al.Relevance of mutations in the TLR4 receptor in patients with gram-negative septic shock.[J]. Arch Intern Med 2002;162(9):1028–1032.
[11] Kiechl S, Lorenz E, Reindl M,et al. Toll-like receptor 4 polymorphisms and atherogenesis.[J]. N Engl J Med 2002;347(3):185–192.
[1] El-Omar EM. The importance of interleukin 1beta in Helicobacter pylori associated disease.[J]. Gut 2001; 48(6): 743–7.
[2] Bidwell J, Keen L, Gallagher G, et al.Cytokine gene polymorphism in human disease: on-line databases, supplement 1. [J].Genes Immun,2001; 2(2): 61–70.
[3] Peek RM Jr,Blaser MJ. Helicobacter pylori and gastrointestinal tract adenocarcinomas.[J].Nat Rev Cancer.2002,2(1):28-37.
[4] Machado JC, Pharoah P, Sousa S, et al.Interleukin 1B and interleukin 1RN polymorphisms are associated with increased risk of gastric carcinoma.[J]. Gastroenterology ,2001; 121(4): 823–9.
[5] Figueiredo C, Machado JC, Pharoah P, et al.Helicobacter pylori and interleukin 1 genotyping: an opportunity to identify high-risk individuals for gastric carcinoma. [J].J Natl Cancer Inst 2002; 94: 1680–7.
[6] Zeng ZR, Hu PJ, Hu S, et al. association of interleukin 1B gene polymorphism and gastric cancer in high and low prevalence regions in China.[J]. Gut .2003,52(12):1684-1689
[7] Shuiping Tu, Govind Bhagat, Guanglin Cui, et al. Wang .Overexpression of interleukin-1[beta] induces gastric in?ammation and cancer and mobilizes myeloid-derived suppressor cells in mice.[J]. Cancer Cell ,2008; 14(5): 408–19.
[8] Shintaro Kamizono, Yuji Hiromatsu, Naoko Seki, et al.A polymorphism of the 5′?anking region of tumour necrosis factorαgene is associated with thyroid-associated ophthalmopathy in Japanese.[J]. Clin Endocrinol 2000; 52(6): 759–64.
[9] Yamaguchi E, Itoh A, Hizawa N, et al.The gene polymorphism of tumor necrosis factor-β, but not that of tumor necrosis factor-α, is associated with the prognosis of sarcoidosis.[J].Chest 2001; 119(3): 753–61.
[10] T. Higuchi, N. Seki, S. Kamizono, et al.Polymorphism of the 5′-?anking region of the human tumor necrosis factor (TNF)-αgene in Japanese.[J]. Tissue Antigens 1998; 51(6): 605–12.
[11] D’Alfonso S, Richiardi PM. A polymorphic variation in a putative regulation box of the TNFαpromoter region. [J].Immunogenet 1994; 39(2): 150–5.
[12] Emad M E,Charles S R, Marilie D G,et al. Increased risk of Noncardia gastric cancer asociated with proinflammatory cytokine gene Polymorphisms.[J]. Gastroenterology,2003,124(5);1193- 1201.
[13] Arbour NC, Lorenz E, Schutte BC, et al.TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. [J].Nat Genet 2000;25(2):187–191.
[14] D Franchimont , S Vermeire, H El Housni, et al.Deficient host-bacteria interactions in in?ammatory bowel disease? The toll-like receptor (TLR)-4 Asp299gly polymorphism is associated with Crohn’s disease and ulcerative colitis.[J]. Gut 2004;53(7):987–992.
[15] Lorenz E, Mira JP, Frees KL et al. Relevance of mutations in the TLR4 receptor in patients with gram-negative septic shock. [J].Arch Intern Med 2002;162(9):1028–1032.
[16] Kiechl S, Lorenz E, Reindl M, et al. Toll-like receptor 4 polymorphisms and atherogenesis.[J]. N Engl J Med 2002;347(3):185–192.
[17] Hold GL, Rabkin CS, Chow WH et al. A functional polymorphism of toll-likereceptor 4 gene increases risk of gastric carcinoma and its precursors.[J]. Gastroenterology 2007;132(3):905–912.
[18] Tahara T, Arisawa T, Wang FY, et al. Toll-like receptor 2–196 to 174del polymorphism influences the susceptibility of Japanese people to gastric cancer .[J].Cancer Sci, 2007, 98(11): 1790–1794.
[19] Ng MT, Van’t Hof R, Crockett JC, et al. Increase in NF-κB binding affinity of the C allelic variant of the Toll-like receptor 9 -1237T/C polymorphism is associated with Helicobacter pylori induced gastric disease.[J]. Infect Immun, 2010,78 (3):1345-52.
[20] Goto Y, Ando T, Yamamoto K, Tamakoshi A et al.Association between serum pepsinogens and polymorphism of PTPN11 encoding SHP-2 among H pylori seropositive Japanese. [J].Int J Cancer. 2006;118(1):203-8
[21] Hishida A, Matsuo K, Goto Y, et al.Associations of a PTPN11 G/A polymorphism at intron 3 with Helicobactor pylori seropositivity, gastric atrophy and gastric cancer in Japanese.[J].BMC Gastroenterology: 2009, 9:51 http://www.biomedcentral.com/1471-230X/9/51
[22] Toru HIYAMA1, Shinji TANAKA, et al.p53 Codon 72 polymorphism in gastric cancer susceptibility in patients with Helicobacter pylori-associated chronic gastritis.[J].Int. J. Cancer:2002, 100(3), 304–308
[23] Nayoung Kim, Sung-Il Cho, Hye Seung Lee, et al.The Discrepancy Between Genetic Polymorphism of p53 Codon 72 and the Expression of p53 Protein in Helicobacter pylori-Associated Gastric Cancer in Korea.[J].Dig Dis Sci :2010, 55(1):101–110
[24] Bond GL, Hu W, Bond EE, et al. A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans.[J].Cell 2004;119(5):591–602.
[25] Xiaoyong Wang, Jing Yang,Bo Ho, et al. Interaction of Helicobacter pylori with Genetic Variants in the MDM2 Promoter, is Associated with Gastric Cancer Susceptibility in Chinese Patients. [J].Helicobacter ;2009 ;14(5): 466–471