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Genetic Instability and Chronic Inflammation in Gastrointestinal Cancers

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Cancer Genome and Tumor Microenvironment

Part of the book series: Cancer Genetics ((CANGENETICS))

Abstract

Genetic instability and inflammation are closely intertwined processes. While the induction of genetic instability in the setting of inflammation is easy to conceptualize, the reverse occurs as well. It has been appreciated for some time now that colon cancers that arise in the setting of DNA mismatch repair (MMR) deficiencies have a significant lymphocyte infiltration, suggesting an inflammatory response. This characteristic is being used clinically by pathologists to identify the approximately 15% of human colon cancers that develop with microsatellite instability (MSI) rather than the more common chromosomal instability. Inactivating mutations or gene silencing of hMLH1 or hMSH2, which are essential for normal MMR, are frequently observed in these cancers and account for the vast majority of hereditary non-polyposis colorectal cancer (HNPCC, or Lynch syndrome I) (Ionov et al. 1993; Thibodeau et al. 1993; Fishel et al. 1993; Leach et al. 1993). How the induction of MSI leads to the increased inflammatory response remains unknown. What is better understood is how chronic inflammatory processes provoke genetic instabilities that lead to the development of cancer.

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References

  • Abraham SC, Park SJ, Lee JH, Mugartegui L, Wu TT (2003) Genetic alterations in gastric adenomas of intestinal and foveolar phenotypes. Mod Pathol 16:786–795.

    PubMed  Google Scholar 

  • Ahuja N, Mohan AL, Li Q, Stolker JM, Herman JG, Hamilton SR, Baylin SB, Issa JP (1997) Association between CpG island methylation and microsatellite instability in colorectal cancer. Cancer Res 57:3370–3374.

    PubMed  CAS  Google Scholar 

  • Akre K, Ekstrom AM, Signorello LB, Hansson LE, Nyren O (2001) Aspirin and risk for gastric cancer: a population-based case-control study in Sweden. Br J Cancer 84:965–968.

    PubMed  CAS  Google Scholar 

  • Anonymous (1994) Live flukes and Helicobacter pylori. IARC Working group on the Evaluation of Carcinogenic Risks to Humans. Lyon. 7–14 June 1994. IARC Monogr Eval Carcinog Risks Hum 61:1–241.

    Google Scholar 

  • Artandi SE, Chang S, Lee SL, Alson S, Gottlieb GJ, Chin L, DePinho RA (2000) Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice. Nature 406:641–645.

    PubMed  CAS  Google Scholar 

  • Aust DE, Terdiman JP, Willenbucher RF, Chang CG, Molinaro-Clark A, Baretton GB, Loehrs U, Waldman FM (2002) The APC/beta-catenin pathway in ulcerative colitis-related colorectal carcinomas: a mutational analysis. Cancer 94:1421–1427.

    PubMed  CAS  Google Scholar 

  • Bader S, Walker M, Hendrich B, Bird A, Bird C, Hooper M, Wyllie A (1999) Somatic frameshift mutations in the MBD4 gene of sporadic colon cancers with mismatch repair deficiency. Oncogene 18:8044–8047.

    PubMed  CAS  Google Scholar 

  • Baek MJ, Kang H, Kim SE, Park JH, Lee JS, Paik YK, Kim H (2001) Expression of hMLH1 is inactivated in the gastric adenomas with enhanced microsatellite instability. Br J Cancer 85:1147–1152.

    PubMed  CAS  Google Scholar 

  • Balkwill F (2002) Tumor necrosis factor or tumor promoting factor? Cytokine Growth Factor Rev 13:135–141.

    PubMed  CAS  Google Scholar 

  • Balkwill FR (2004) Inflammatory cytokines: their role in tumor growth and progression. In: Cancer and Inflammation. Birkhauser Verlag Basel, Basel.

    Google Scholar 

  • Banchereau J and Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392:245–252.

    PubMed  CAS  Google Scholar 

  • Bargen JA (1928) Chronic ulcerative colitis associated with malignant disease. Arch Surg 17:561–576.

    Google Scholar 

  • Baumgart DC and Carding SR (2007) Inflammatory bowel disease: cause and immunobiology. Lancet 369:1627–1640.

    PubMed  CAS  Google Scholar 

  • Baylin SB and Herman JG (2000) DNA hypermethylation in tumorigenesis: epigenetics joins genetics. Trends Genet 16:168–174.

    PubMed  CAS  Google Scholar 

  • Bello MJ, Alonso ME, Aminoso C, Anselmo NP, Arjona D, Gonzalez-Gomez P, Lopez-Marin I, de Campos JM, Gutierrez M, Isla A, Kusak ME, Lassaletta L, Sarasa JL, Vaquero J, Casartelli C, Rey JA (2004) Hypermethylation of the DNA repair gene MGMT: association with TP53 G:C to A:T transitions in a series of 469 nervous system tumors. Mutat Res 554:23–32.

    PubMed  CAS  Google Scholar 

  • Berger FG (2004) The interleukin-6 gene: a susceptibility factor that may contribute to racial and ethnic disparities in breast cancer mortality. Breast Cancer Res Treat 88:281–285.

    PubMed  CAS  Google Scholar 

  • Bharadwaj R and Yu H (2004) The spindle checkpoint, aneuploidy, and cancer. Oncogene 23:2016–2027.

    PubMed  CAS  Google Scholar 

  • Blair IA (2001) Lipid hydroperoxide-mediated DNA damage. Exp Gerontol 36:1473–1481.

    PubMed  CAS  Google Scholar 

  • Blair IA (2008) DNA adducts with lipid peroxidation products. J Biol Chem 283:15545–15549.

    PubMed  CAS  Google Scholar 

  • Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, Meltzer SJ, Rodriguez-Bigas MA, Fodde R, Ranzani GN, Srivastava S (1998) A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res 58:5248–5257.

    PubMed  CAS  Google Scholar 

  • Boland CR, Luciani MG, Gasche C, Goel A (2005) Infection, inflammation, and gastrointestinal cancer. Gut 54:1321–1331.

    PubMed  CAS  Google Scholar 

  • Bommert K, Bargou RC, Stuhmer T (2006) Signalling and survival pathways in multiple myeloma. Eur J Cancer 42:1574–1580.

    PubMed  CAS  Google Scholar 

  • Breivik J and Gaudernack G (1999) Genomic instability, DNA methylation, and natural selection in colorectal carcinogenesis. Semin Cancer Biol 9:245–254.

    PubMed  CAS  Google Scholar 

  • Brentnall TA, Crispin DA, Rabinovitch PS, Haggitt RC, Rubin CE, Stevens AC, Burmer GC (1994) Mutations in the p53 gene: an early marker of neoplastic progression in ulcerative colitis. Gastroenterology 107:369–378.

    PubMed  CAS  Google Scholar 

  • Burmer GC, Rabinovitch PS, Haggitt RC, Crispin DA, Brentnall TA, Kolli VR, Stevens AC, Rubin CE (1992) Neoplastic progression in ulcerative colitis: histology, DNA content, and loss of a p53 allele. Gastroenterology 103:1602–1610.

    PubMed  CAS  Google Scholar 

  • Cahill DP, Lengauer C, Yu J, Riggins GJ, Willson JK, Markowitz SD, Kinzler KW, Vogelstein B (1998) Mutations of mitotic checkpoint genes in human cancers. Nature 392:300–303.

    PubMed  CAS  Google Scholar 

  • Cahill DP, Kinzler KW, Vogelstein B, Lengauer C (1999) Genetic instability and darwinian selection in tumours. Trends Cell Biol 9:M57–60.

    PubMed  CAS  Google Scholar 

  • Calin GA, Gafa R, Tibiletti MG, Herlea V, Becheanu G, Cavazzini L, Barbanti-Brodano G, Nenci I, Negrini M, Lanza G (2000) Genetic progression in microsatellite instability high (MSI-H) colon cancers correlates with clinico-pathological parameters: A study of the TGRbetaRII, BAX, hMSH3, hMSH6, IGFIIR and BLM genes. Int J Cancer 89:230–235.

    PubMed  CAS  Google Scholar 

  • Cassaro M, Rugge M, Gutierrez O, Leandro G, Graham DY, Genta RM (2000) Topographic patterns of intestinal metaplasia and gastric cancer. Am J Gastroenterol 95:1431–1438.

    PubMed  CAS  Google Scholar 

  • Censini S, Lange C, Xiang Z, Crabtree JE, Ghiara P, Borodovsky M, Rappuoli R, Covacci A (1996) cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors. Proc Natl Acad Sci U S A 93:14648–14653.

    PubMed  CAS  Google Scholar 

  • Chan AO, Chu KM, Huang C, Lam KF, Leung SY, Sun YW, Ko S, Xia HH, Cho CH, Hui WM, Lam SK, Rashid A (2007) Association between Helicobacter pylori infection and interleukin 1beta polymorphism predispose to CpG island methylation in gastric cancer. Gut 56:595–597.

    PubMed  Google Scholar 

  • Chang CL, Marra G, Chauhan DP, Ha HT, Chang DK, Ricciardiello L, Randolph A, Carethers JM, Boland CR (2002) Oxidative stress inactivates the human DNA mismatch repair system. Am J Physiol Cell Physiol 283:C148–154.

    PubMed  CAS  Google Scholar 

  • Charo IF and Ransohoff RM (2006) The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med 354:610–621.

    PubMed  CAS  Google Scholar 

  • Chell SD, Witherden IR, Dobson RR, Moorghen M, Herman AA, Qualtrough D, Williams AC, Paraskeva C (2006) Increased EP4 receptor expression in colorectal cancer progression promotes cell growth and anchorage independence. Cancer Res 66:3106–3113.

    PubMed  CAS  Google Scholar 

  • Chung YJ, Park SW, Song JM, Lee KY, Seo EJ, Choi SW, Rhyu MG (1997) Evidence of genetic progression in human gastric carcinomas with microsatellite instability. Oncogene 15:1719–1726.

    PubMed  CAS  Google Scholar 

  • Cohn SM, Schloemann S, Tessner T, Seibert K, Stenson WF (1997) Crypt stem cell survival in the mouse intestinal epithelium is regulated by prostaglandins synthesized through cyclooxygenase-1. J Clin Invest 99:1367–1379.

    PubMed  CAS  Google Scholar 

  • Corn PG, Summers MK, Fogt F, Virmani AK, Gazdar AF, Halazonetis TD, El-Deiry WS (2003) Frequent hypermethylation of the 5' CpG island of the mitotic stress checkpoint gene Chfr in colorectal and non-small cell lung cancer. Carcinogenesis 24:47–51.

    PubMed  CAS  Google Scholar 

  • Correa P (1992) Human gastric carcinogenesis: a multistep and multifactorial process– First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. Cancer Res 52:6735–6740.

    PubMed  CAS  Google Scholar 

  • Correa P (1995) Helicobacter pylori and gastric carcinogenesis. Am J Surg Pathol 19:S37–S43.

    PubMed  Google Scholar 

  • Correa P and Houghton J (2007) Carcinogenesis of Helicobacter pylori. Gastroenterology 133:659–672.

    PubMed  CAS  Google Scholar 

  • Correa P and Shiao Y-H (1994) Phenotypic and genotypic events in gastric carcinogenesis. Cancer Res 54 (Supplement):1941–1943.

    Google Scholar 

  • Coussens LM and Werb Z (2002) Inflammation and cancer. Nature 420:860–867.

    PubMed  CAS  Google Scholar 

  • Cover TL and Blanke SR (2005) Helicobacter pylori VacA, a paradigm for toxin multifunctionality. Nat Rev Microbiol 3:320–332.

    PubMed  CAS  Google Scholar 

  • Crabtree JE, Covacci A, Farmery SM, Xiang Z, Tompkins DS, Perry S, Lindley IJ, Rappuoli R (1995) Helicobacter pylori induced interleukin-8 expression in gastric epithelial cells is associated with CagA positive phenotype. J Clin Pathol 48:41–45.

    PubMed  CAS  Google Scholar 

  • Crabtree JE, Wyatt JI, Trejdosiewicz LK, Peichl P, Nichols PH, Ramsay N, Primrose JN, Lindley IJ (1994) Interleukin-8 expression in Helicobacter pylori infected, normal, and neoplastic gastroduodenal mucosa. J Clin Pathol 47:61–66.

    PubMed  CAS  Google Scholar 

  • Crofford LJ (2001) Prostaglandin biology. Gastroenterol Clin North Am 30:863–876.

    PubMed  CAS  Google Scholar 

  • Cruz-Correa M, Cui H, Giardiello FM, Powe NR, Hylind L, Robinson A, Hutcheon DF, Kafonek DR, Brandenburg S, Wu Y, He X, Feinberg AP (2004) Loss of imprinting of insulin growth factor II gene: a potential heritable biomarker for colon neoplasia predisposition. Gastroenterology 126:964–970.

    PubMed  CAS  Google Scholar 

  • Cui H, Onyango P, Brandenburg S, Wu Y, Hsieh CL, Feinberg AP (2002) Loss of imprinting in colorectal cancer linked to hypomethylation of H19 and IGF2. Cancer Res 62:6442–6446.

    PubMed  CAS  Google Scholar 

  • Cunningham JM, Christensen ER, Tester DJ, Kim CY, Roche PC, Burgart LJ, Thibodeau SN (1998) Hypermethylation of the hMLH1 promoter in colon cancer with microsatellite instability. Cancer Res 58:3455–3460.

    PubMed  CAS  Google Scholar 

  • Delaunoit T, Limburg PJ, Goldberg RM, Lymp JF, Loftus EV, Jr. (2006) Colorectal cancer prognosis among patients with inflammatory bowel disease. Clin Gastroenterol Hepatol 4:335–342.

    PubMed  Google Scholar 

  • Devroede GJ, Taylor WF, Sauer WG, Jackman RJ, Stickler GB (1971) Cancer risk and life expectancy of children with ulcerative colitis. N Engl J Med 285:17–21.

    PubMed  CAS  Google Scholar 

  • Dixon MF (1995) Histological responses to Helicobacter pylori infection: gastritis, atrophy and preneoplasia. Baillieres Clin Gastroenterol 9:467–486.

    PubMed  CAS  Google Scholar 

  • Dixon MF, Genta RM, Yardley JH, Correa P (1996) Classification and grading of gastritis. The updated Sydney system. International workshop on the histopathology of gastritis, Houston 1994. Am J Surg Pathol 20:1161–1181.

    PubMed  CAS  Google Scholar 

  • Eaden JA, Abrams KR, Mayberry JF (2001) The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut 48:526–535.

    PubMed  CAS  Google Scholar 

  • Eck M, Greiner A, Schmausser B, Eck H, Kolve M, Fischbach W, Strecker P, Muller-Hermelink HK (1999) Evaluation of Helicobacter pylori in gastric MALT-type lymphoma: differences between histologic and serologic diagnosis. Mod Pathol 12:1148–1151.

    PubMed  CAS  Google Scholar 

  • Edmonston TB, Cuesta KH, Burkholder S, Barusevicius A, Rose D, Kovatich AJ, Boman B, Fry R, Fishel R, Palazzo JP (2000) Colorectal carcinomas with high microsatellite instability: defining a distinct immunologic and molecular entity with respect to prognostic markers. Hum Pathol 31:1506–1514.

    PubMed  CAS  Google Scholar 

  • Ejima Y, Yang L, Sasaki MS (2000) Aberrant splicing of the ATM gene associated with shortening of the intronic mononucleotide tract in human colon tumor cell lines: a novel mutation target of microsatellite instability. Int J Cancer 86:262–268.

    PubMed  CAS  Google Scholar 

  • Ekbom A, Helmick C, Zack M, Adami HO (1990) Ulcerative colitis and colorectal cancer. A population-based study. N Engl J Med 323:1228–1233.

    PubMed  CAS  Google Scholar 

  • El-Omar EM (2006) Role of host genes in sporadic gastric cancer. Best Pract Res Clin Gastroenterol 20:675–686.

    PubMed  CAS  Google Scholar 

  • 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, Jr., Rabkin CS (2000) Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature 404:398–402.

    PubMed  CAS  Google Scholar 

  • El-Omar EM, Rabkin CS, Gammon MD, Vaughan TL, Risch HA, Schoenberg JB, Stanford JL, Mayne ST, Goedert J, Blot WJ, Fraumeni JF, Jr., Chow WH (2003) Increased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms. Gastroenterology 124:1193–1201.

    PubMed  CAS  Google Scholar 

  • Engelhardt M, Drullinsky P, Guillem J, Moore MA (1997) Telomerase and telomere length in the development and progression of premalignant lesions to colorectal cancer. Clin Cancer Res 3:1931–1941.

    PubMed  CAS  Google Scholar 

  • Esteller M, Tortola S, Toyota M, Capella G, Peinado MA, Baylin SB, Herman JG (2000) Hypermethylation-associated inactivation of p14(ARF) is independent of p16(INK4a) methylation and p53 mutational status. Cancer Res 60:129–133.

    PubMed  CAS  Google Scholar 

  • Esteller M, Cordon-Cardo C, Corn PG, Meltzer SJ, Pohar KS, Watkins DN, Capella G, Peinado MA, Matias-Guiu X, Prat J, Baylin SB, Herman JG (2001a) p14ARF silencing by promoter hypermethylation mediates abnormal intracellular localization of MDM2. Cancer Res 61:2816–2821.

    PubMed  CAS  Google Scholar 

  • Esteller M, Corn PG, Baylin SB, Herman JG (2001b) A gene hypermethylation profile of human cancer. Cancer Res 61:3225–3229.

    PubMed  CAS  Google Scholar 

  • Fang DC, Jass JR, Wang DX, Zhou XD, Luo YH, Young J (1999) Infrequent loss of heterozygosity of APC/MCC and DCC genes in gastric cancer showing DNA microsatellite instability. J Clin Pathol 52:504–508.

    PubMed  CAS  Google Scholar 

  • Farinati F, Cardin R, Degan P, Rugge M, Mario FD, Bonvicini P, Naccarato R (1998) Oxidative DNA damage accumulation in gastric carcinogenesis. Gut 42:351–356.

    PubMed  CAS  Google Scholar 

  • Farinati F, Cardin R, Bortolami M, Nitti D, Basso D, de Bernard M, Cassaro M, Sergio A, Rugge M (2008) Oxidative DNA damage in gastric cancer: CagA status and OGG1 gene polymorphism. Int J Cancer 123:51–55.

    PubMed  CAS  Google Scholar 

  • Farrow B and Evers BM (2002) Inflammation and the development of pancreatic cancer. Surg Oncol 10:153–169.

    PubMed  Google Scholar 

  • Federico A, Morgillo F, Tuccillo C, Ciardiello F, Loguercio C (2007) Chronic inflammation and oxidative stress in human carcinogenesis. Int J Cancer 121:2381–2386.

    PubMed  CAS  Google Scholar 

  • Fischbach W, Goebeler-Kolve ME, Dragosics B, Greiner A, Stolte M (2004) Long term outcome of patients with gastric marginal zone B cell lymphoma of mucosa associated lymphoid tissue (MALT) following exclusive Helicobacter pylori eradication therapy: experience from a large prospective series. Gut 53:34–37.

    PubMed  CAS  Google Scholar 

  • Fischer W, Gebert B, Haas R (2004) Novel activities of the Helicobacter pylori vacuolating cytotoxin: from epithelial cells towards the immune system. Int J Med Microbiol 293:539–547.

    PubMed  CAS  Google Scholar 

  • Fishel R, Lescoe MK, Rao MR, Copeland NG, Jenkins NA, Garber J, Kane M, Kolodner R (1993) The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell 75:1027–1038.

    PubMed  CAS  Google Scholar 

  • Fleisher AS, Esteller M, Harpaz N, Leytin A, Rashid A, Xu Y, Liang J, Stine OC, Yin J, Zou TT, Abraham JM, Kong D, Wilson KT, James SP, Herman JG, Meltzer SJ (2000) Microsatellite instability in inflammatory bowel disease-associated neoplastic lesions is associated with hypermethylation and diminished expression of the DNA mismatch repair gene, hMLH1. Cancer Res 60:4864–4868.

    PubMed  CAS  Google Scholar 

  • Fleisher AS, Esteller M, Tamura G, Rashid A, Stine OC, Yin J, Zou TT, Abraham JM, Kong D, Nishizuka S, James SP, Wilson KT, Herman JG, Meltzer SJ (2001) Hypermethylation of the hMLH1 gene promoter is associated with microsatellite instability in early human gastric neoplasia. Oncogene 20:329–335.

    PubMed  CAS  Google Scholar 

  • Forman D, Newell DG, Fullerton F, Yarnell JW, Stacey AR, Wald N, Sitas F (1991) Association between infection with Helicobacter pylori and risk of gastric cancer: evidence from a prospective investigation. BMJ 302:1302–1305.

    PubMed  CAS  Google Scholar 

  • Fosslien E (2001) Review: molecular pathology of cyclooxygenase-2 in cancer-induced angiogenesis. Ann Clin Lab Sci 31:325–348.

    PubMed  CAS  Google Scholar 

  • Fu S, Ramanujam KS, Wong A, Fantry GT, Drachenberg CB, James SP, Meltzer SJ, Wilson KT (1999) Increased expression and cellular localization of inducible nitric oxide synthase and cyclooxygenase 2 in Helicobacter pylori gastritis. Gastroenterology 116:1319–1329.

    PubMed  CAS  Google Scholar 

  • Gebert B, Fischer W, Haas R (2004) The Helicobacter pylori vacuolating cytotoxin: from cellular vacuolation to immunosuppressive activities. Rev Physiol Biochem Pharmacol 152:205–220.

    PubMed  CAS  Google Scholar 

  • Gebert B, Fischer W, Weiss E, Hoffmann R, Haas R (2003) Helicobacter pylori vacuolating cytotoxin inhibits T lymphocyte activation. Science 301:1099–1102.

    PubMed  CAS  Google Scholar 

  • Gerson SL (2004) MGMT: its role in cancer aetiology and cancer therapeutics. Nat Rev Cancer 4:296–307.

    PubMed  CAS  Google Scholar 

  • Giannakis M, Chen SL, Karam SM, Engstrand L, Gordon JI (2008) Helicobacter pylori evolution during progression from chronic atrophic gastritis to gastric cancer and its impact on gastric stem cells. Proc Natl Acad Sci U S A 105:4358–4363.

    PubMed  CAS  Google Scholar 

  • Giardiello FM, Yang VW, Hylind LM, Krush AJ, Petersen GM, Trimbath JD, Piantadosi S, Garrett E, Geiman DE, Hubbard W, Offerhaus GJ, Hamilton SR (2002) Primary chemoprevention of familial adenomatous polyposis with sulindac. N Engl J Med 346:1054–1059.

    PubMed  CAS  Google Scholar 

  • Gisselsson D, Jonson T, Petersen A, Strombeck B, Dal Cin P, Hoglund M, Mitelman F, Mertens F, Mandahl N (2001) Telomere dysfunction triggers extensive DNA fragmentation and evolution of complex chromosome abnormalities in human malignant tumors. Proc Natl Acad Sci U S A 98:12683–12688.

    PubMed  CAS  Google Scholar 

  • Gologan A, Graham DY, Sepulveda AR (2005) Molecular Markers in Helicobacter pylori-Associated Gastric Carcinogenesis. Clin Lab Med 25:197–222.

    PubMed  Google Scholar 

  • Gonzalez-Perez A, Garcia Rodriguez LA, Lopez-Ridaura R (2003) Effects of non-steroidal anti-inflammatory drugs on cancer sites other than the colon and rectum: a meta-analysis. BMC Cancer 3:28.

    PubMed  Google Scholar 

  • Grady WM, Rajput A, Myeroff L, Liu DF, Kwon K, Willis J, Markowitz S (1998) Mutation of the type II transforming growth factor-beta receptor is coincident with the transformation of human colon adenomas to malignant carcinomas. Cancer Res 58:3101–3104.

    PubMed  CAS  Google Scholar 

  • Greenwald BD, Harpaz N, Yin J, Huang Y, Tong Y, Brown VL, McDaniel T, Newkirk C, Resau JH, Meltzer SJ (1992) Loss of heterozygosity affecting the p53, Rb, and mcc/apc tumor suppressor gene loci in dysplastic and cancerous ulcerative colitis. Cancer Res 52:741–745.

    PubMed  CAS  Google Scholar 

  • Grisham MB, Jourd’heuil D, Wink DA (2000) Review article: chronic inflammation and reactive oxygen and nitrogen metabolism–implications in DNA damage and mutagenesis. Aliment Pharmacol Ther 14 Suppl 1:3–9.

    PubMed  CAS  Google Scholar 

  • Hahm KB, Lee KJ, Choi SY, Kim JH, Cho SW, Yim H, Park SJ, Chung MH (1997) Possibility of chemoprevention by the eradication of Helicobacter pylori: oxidative DNA damage and apoptosis in H. pylori infection. Am J Gastroenterol 92:1853–1857.

    PubMed  CAS  Google Scholar 

  • Hamamoto T, Yokozaki H, Semba S, Yasui W, Yunotani S, Miyazaki K, Tahara E (1997) Altered microsatellites in incomplete-type intestinal metaplasia adjacent to primary gastric cancers. J Clin Pathol 50:841–846.

    PubMed  CAS  Google Scholar 

  • Handa O, Naito Y, Yoshikawa T (2007) CagA protein of Helicobacter pylori: a hijacker of gastric epithelial cell signaling. Biochem Pharmacol 73:1697–1702.

    PubMed  CAS  Google Scholar 

  • Hart AL, Lammers K, Brigidi P, Vitali B, Rizzello F, Gionchetti P, Campieri M, Kamm MA, Knight SC, Stagg AJ (2004) Modulation of human dendritic cell phenotype and function by probiotic bacteria. Gut 53:1602–1609.

    PubMed  CAS  Google Scholar 

  • Hatakeyama M and Higashi H (2005) Helicobacter pylori CagA: a new paradigm for bacterial carcinogenesis. Cancer Sci 96:835–843.

    PubMed  CAS  Google Scholar 

  • Hayden JD, Martin IG, Cawkwell L, Quirke P (1998) The role of microsatellite instability in gastric carcinoma. Gut 42:300–303.

    PubMed  CAS  Google Scholar 

  • Heinen CD, Schmutte C, Fishel R (2002) DNA repair and tumorigenesis: lessons from hereditary cancer syndromes. Cancer Biol Ther 1:477–485.

    PubMed  Google Scholar 

  • Hermsen M, Postma C, Baak J, Weiss M, Rapallo A, Sciutto A, Roemen G, Arends JW, Williams R, Giaretti W, De Goeij A, Meijer G (2002) Colorectal adenoma to carcinoma progression follows multiple pathways of chromosomal instability. Gastroenterology 123:1109–1119.

    PubMed  CAS  Google Scholar 

  • Hofseth LJ, Khan MA, Ambrose M, Nikolayeva O, Xu-Welliver M, Kartalou M, Hussain SP, Roth RB, Zhou X, Mechanic LE, Zurer I, Rotter V, Samson LD, Harris CC (2003) The adaptive imbalance in base excision-repair enzymes generates microsatellite instability in chronic inflammation. J Clin Invest 112:1887–1894.

    PubMed  CAS  Google Scholar 

  • Hollstein MC, Smits AM, Galiana C, Yamasaki H, Bos JL, Mandard A, Partensky C, Montesano R (1988) Amplification of epidermal growth factor receptor gene but no evidence of ras mutations in primary human esophageal cancers. Cancer Res 48:5119–5123.

    PubMed  CAS  Google Scholar 

  • Holzmann K, Klump B, Borchard F, Hsieh CJ, Kuhn A, Gaco V, Gregor M, Porschen R (1998) Comparative analysis of histology, DNA content, p53 and Ki-ras mutations in colectomy specimens with long-standing ulcerative colitis. Int J Cancer 76:1–6.

    PubMed  CAS  Google Scholar 

  • Honda T, Tamura G, Waki T, Kawata S, Nishizuka S, Motoyama T (2004) Promoter hypermethylation of the Chfr gene in neoplastic and non-neoplastic gastric epithelia. Br J Cancer 90:2013–2016.

    PubMed  CAS  Google Scholar 

  • Houghton J, Stoicov C, Nomura S, Rogers AB, Carlson J, Li H, Cai X, Fox JG, Goldenring JR, Wang TC (2004) Gastric cancer originating from bone marrow-derived cells. Science 306:1568–1571.

    PubMed  CAS  Google Scholar 

  • Howes N, Lerch MM, Greenhalf W, Stocken DD, Ellis I, Simon P, Truninger K, Ammann R, Cavallini G, Charnley RM, Uomo G, Delhaye M, Spicak J, Drumm B, Jansen J, Mountford R, Whitcomb DC, Neoptolemos JP (2004) Clinical and genetic characteristics of hereditary pancreatitis in Europe. Clin Gastroenterol Hepatol 2:252–261.

    PubMed  CAS  Google Scholar 

  • Huang J, Papadopoulos N, McKinley AJ, Farrington SM, Curtis LJ, Wyllie AH, Zheng S, Willson JK, Markowitz SD, Morin P, Kinzler KW, Vogelstein B, Dunlop MG (1996) APC mutations in colorectal tumors with mismatch repair deficiency. Proc Natl Acad Sci U S A 93:9049–9054.

    PubMed  CAS  Google Scholar 

  • Huang JQ, Sridhar S, Chen Y, Hunt RH (1998) Meta-analysis of the relationship between Helicobacter pylori seropositivity and gastric cancer. Gastroenterology 114:1169–1179.

    PubMed  CAS  Google Scholar 

  • Hunt JD, Mera R, Strimas A, Gillespie AT, Ruiz B, Correa P, Fontham ET (2001) KRAS mutations are not predictive for progression of preneoplastic gastric lesions. Cancer Epidemiol Biomarkers Prev 10:79–80.

    PubMed  CAS  Google Scholar 

  • Husain SS, Szabo IL, Tamawski AS (2002) NSAID inhibition of GI cancer growth: clinical implications and molecular mechanisms of action. Am J Gastroenterol 97:542–553.

    PubMed  CAS  Google Scholar 

  • Hussain SP, Amstad P, Raja K, Ambs S, Nagashima M, Bennett WP, Shields PG, Ham AJ, Swenberg JA, Marrogi AJ, Harris CC (2000) Increased p53 mutation load in noncancerous colon tissue from ulcerative colitis: a cancer-prone chronic inflammatory disease. Cancer Res 60:3333–3337.

    PubMed  CAS  Google Scholar 

  • Hussain SP, Hofseth LJ, Harris CC (2003) Radical causes of cancer. Nat Rev Cancer 3:276–285.

    PubMed  CAS  Google Scholar 

  • Iguchi C, Nio Y, Takeda H, Yamasawa K, Hirahara N, Toga T, Itakura M, Tamura K (2001) Plant polysaccharide PSK: cytostatic effects on growth and invasion; modulating effect on the expression of HLA and adhesion molecules on human gastric and colonic tumor cell surface. Anticancer Res 21:1007–1013.

    PubMed  CAS  Google Scholar 

  • Imatani A, Sasano H, Asaki S, Toyota T, Saito M, Masuda T, Nagura H (1996) Analysis of p53 abnormalities in endoscopic gastric biopsies. Anticancer Res 16:2049–2056.

    PubMed  CAS  Google Scholar 

  • Ionov Y, Peinado MA, Malkhosyan S, Shibata D, Perucho M (1993) Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature 363:558–561.

    PubMed  CAS  Google Scholar 

  • Itzkowitz SH (2006) Molecular biology of dysplasia and cancer in inflammatory bowel disease. Gastroenterol Clin North Am 35:553–571.

    PubMed  Google Scholar 

  • Jass JR (2004) Hyperplastic polyps and colorectal cancer: is there a link? Clin Gastroenterol Hepatol 2:1–8.

    PubMed  Google Scholar 

  • Jass JR, Whitehall VL, Young J, Leggett BA (2002) Emerging concepts in colorectal neoplasia. Gastroenterology 123:862–876.

    PubMed  CAS  Google Scholar 

  • Jess T, Loftus EV, Jr., Velayos FS, Harmsen WS, Zinsmeister AR, Smyrk TC, Schleck CD, Tremaine WJ, Melton LJ, 3rd, Munkholm P, Sandborn WJ (2006) Risk of intestinal cancer in inflammatory bowel disease: a population-based study from olmsted county, Minnesota. Gastroenterology 130:1039–1046.

    PubMed  Google Scholar 

  • Jiricny J and Marra G (2003) DNA repair defects in colon cancer. Curr Opin Genet Dev 13:61–69.

    Google Scholar 

  • Jones S, Emmerson P, Maynard J, Best JM, Jordan S, Williams GT, Sampson JR, Cheadle JP (2002) Biallelic germline mutations in MYH predispose to multiple colorectal adenoma and somatic G:C -> T:A mutations. Hum Mol Genet 11:2961–2967.

    PubMed  CAS  Google Scholar 

  • Kambara T, Whitehall VL, Spring KJ, Barker MA, Arnold S, Wynter CV, Matsubara N, Tanaka N, Young JP, Leggett BA, Jass JR (2004) Role of inherited defects of MYH in the development of sporadic colorectal cancer. Genes Chromosomes Cancer 40:1–9.

    PubMed  CAS  Google Scholar 

  • Kambayashi T, Alexander HR, Fong M, Strassmann G (1995) Potential involvement of IL-10 in suppressing tumor-associated macrophages. Colon-26-derived prostaglandin E2 inhibits TNF-alpha release via a mechanism involving IL-10. J Immunol 154:3383–3390.

    PubMed  CAS  Google Scholar 

  • Kang GH, Shim YH, Jung HY, Kim WH, Ro JY, Rhyu MG (2001) CpG island methylation in premalignant stages of gastric carcinoma. Cancer Res 61:2847–2851.

    PubMed  CAS  Google Scholar 

  • Kang GH, Lee S, Kim JS, Jung HY (2003) Profile of aberrant CpG island methylation along the multistep pathway of gastric carcinogenesis. Lab Invest 83:635–641.

    PubMed  CAS  Google Scholar 

  • Karrasch T and Jobin C (2008) NF-kappaB and the intestine: friend or foe? Inflamm Bowel Dis 14:114–124.

    PubMed  Google Scholar 

  • Kashiwagi K, Watanabe M, Ezaki T, Kanai T, Ishii H, Mukai M, Hibi T (2000) Clinical usefulness of microsatellite instability for the prediction of gastric adenoma or adenocarcinoma in patients with chronic gastritis. Br J Cancer 82:1814–1818.

    PubMed  CAS  Google Scholar 

  • Katoh M (2007) Dysregulation of stem cell signaling network due to germline mutation, SNP, Helicobacter pylori infection, epigenetic change and genetic alteration in gastric cancer. Cancer Biol Ther 6:832–839.

    PubMed  CAS  Google Scholar 

  • Keim V, Witt H, Bauer N, Bodeker H, Rosendahl J, Teich N, Mossner J (2003) The course of genetically determined chronic pancreatitis. JOP 4:146–154.

    PubMed  Google Scholar 

  • Kim JJ, Baek MJ, Kim L, Kim NG, Lee YC, Song SY, Noh SH, Kim H (1999) Accumulated frameshift mutations at coding nucleotide repeats during the progression of gastric carcinoma with microsatellite instability. Lab Invest 79:1113–1120.

    PubMed  CAS  Google Scholar 

  • Kim HS, Woo DK, Bae SI, Kim YI, Kim WH (2000) Microsatellite instability in the adenoma-carcinoma sequence of the stomach. Lab Invest 80:57–64.

    PubMed  CAS  Google Scholar 

  • Kim JJ, Tao H, Carloni E, Leung WK, Graham DY, Sepulveda AR (2002a) Helicobacter pylori impairs DNA mismatch repair in gastric epithelial cells. Gastroenterology 123:542–553.

    PubMed  CAS  Google Scholar 

  • Kim JS, Chung SJ, Choi YS, Cheon JH, Kim CW, Kim SG, Jung HC, Song IS (2007) Helicobacter pylori eradication for low-grade gastric mucosa-associated lymphoid tissue lymphoma is more successful in inducing remission in distal compared to proximal disease. Br J Cancer 96:1324–1328.

    PubMed  CAS  Google Scholar 

  • Kim SS, Bhang CS, Min KO, Chae HS, Choi SW, Lee CD, Lim KW, Chung IS, Park DH (2002b) p53 mutations and microsatellite instabilities in the subtype of intestinal metaplasia of the stomach. J Korean Med Sci 17:490–496.

    PubMed  CAS  Google Scholar 

  • Kimura K (2000) Gastritis and gastric cancer. Asia. Gastroenterol Clin North Am 29:609–621.

    PubMed  CAS  Google Scholar 

  • Kobayashi K, Okamoto T, Takayama S, Akiyama M, Ohno T, Yamada H (2000) Genetic instability in intestinal metaplasia is a frequent event leading to well-differentiated early adenocarcinoma of the stomach. Eur J Cancer 36:1113–1119.

    PubMed  CAS  Google Scholar 

  • Kodama K, Sumii K, Kawano M, Kido T, Nojima K, Sumii M, Haruma K, Yoshihara M, Chayama K (2003) Gastric juice nitrite and vitamin C in patients with gastric cancer and atrophic gastritis: is low acidity solely responsible for cancer risk? Eur J Gastroenterol Hepatol 15:987–993.

    PubMed  CAS  Google Scholar 

  • Koizumi K, Hojo S, Akashi T, Yasumoto K, Saiki I (2007) Chemokine receptors in cancer metastasis and cancer cell-derived chemokines in host immune response. Cancer Sci 98:1652–1658.

    PubMed  CAS  Google Scholar 

  • Kolodner RD and Marsischky GT (1999) Eukaryotic DNA mismatch repair. Curr Opin Genet Dev 9:89–96.

    PubMed  CAS  Google Scholar 

  • Kucharzik T, Lugering N, Winde G, Domschke W, Stoll R (1997) Colon carcinoma cell lines stimulate monocytes and lamina propria mononuclear cells to produce IL-10. Clin Exp Immunol 110:296–302.

    PubMed  CAS  Google Scholar 

  • Kuismanen SA, Holmberg MT, Salovaara R, de la Chapelle A, Peltomaki P (2000) Genetic and epigenetic modification of MLH1 accounts for a major share of microsatellite-unstable colorectal cancers. Am J Pathol 156:1773–1779.

    PubMed  CAS  Google Scholar 

  • Kune GA, Kune S, Watson LF (1988) Colorectal cancer risk, chronic illnesses, operations, and medications: case control results from the Melbourne Colorectal Cancer Study. Cancer Res 48:4399–4404.

    PubMed  CAS  Google Scholar 

  • Kuroki T, Trapasso F, Yendamuri S, Matsuyama A, Alder H, Mori M, Croce CM (2003) Allele loss and promoter hypermethylation of VHL, RAR-beta, RASSF1A, and FHIT tumor suppressor genes on chromosome 3p in esophageal squamous cell carcinoma. Cancer Res 63:3724–3728.

    PubMed  CAS  Google Scholar 

  • Langman MJ, Cheng KK, Gilman EA, Lancashire RJ (2000) Effect of anti-inflammatory drugs on overall risk of common cancer: case-control study in general practice research database. BMJ 320:1642–1646.

    PubMed  CAS  Google Scholar 

  • Leach FS, Nicolaides NC, Papadopoulos N, Liu B, Jen J, Parsons R, Peltomaki P, Sistonen P, Aaltonen LA, Nystrom-Lahti M, Guan XY, Zhang J, Meltzer PS, Yu JW, Kao FT, Chen DJ, Cerosaletti KM, Fournier RE, Todd S, Lewis T, Leach RJ, Naylor SL, Weissenbach J, Mecklin JP, Järvinen H, Petersen GM, Hamilton SR, Trent JM, de la Chapelle A, Kinzler KW, Vogelstein B (1993) Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell 75:1215–1225.

    PubMed  CAS  Google Scholar 

  • Leahy KM, Ornberg RL, Wang Y, Zweifel BS, Koki AT, Masferrer JL (2002) Cyclooxygenase-2 inhibition by celecoxib reduces proliferation and induces apoptosis in angiogenic endothelial cells in vivo. Cancer Res 62:625–631.

    PubMed  CAS  Google Scholar 

  • Lee HS, Choi SI, Lee HK, Kim HS, Yang HK, Kang GH, Kim YI, Lee BL, Kim WH (2002a) Distinct clinical features and outcomes of gastric cancers with microsatellite instability. Mod Pathol 15:632–640.

    PubMed  Google Scholar 

  • Lee JH, Abraham SC, Kim HS, Nam JH, Choi C, Lee MC, Park CS, Juhng SW, Rashid A, Hamilton SR, Wu TT (2002b) Inverse relationship between APC gene mutation in gastric adenomas and development of adenocarcinoma. Am J Pathol 161:611–618.

    PubMed  CAS  Google Scholar 

  • Lee JH, Park SJ, Abraham SC, Seo JS, Nam JH, Choi C, Juhng SW, Rashid A, Hamilton SR, Wu TT (2004) Frequent CpG island methylation in precursor lesions and early gastric adenocarcinomas. Oncogene 23:4646–4654.

    PubMed  CAS  Google Scholar 

  • Lengauer C, Kinzler KW, Vogelstein B (1997) Genetic instability in colorectal cancers. Nature 386:623–627.

    PubMed  CAS  Google Scholar 

  • Lengauer C, Kinzler KW, Vogelstein B (1998) Genetic instabilities in human cancers. Nature 396:643–649.

    PubMed  CAS  Google Scholar 

  • Leung WK, Kim JJ, Kim JG, Graham DY, Sepulveda AR (2000) Microsatellite instability in gastric intestinal metaplasia in patients with and without gastric cancer. Am J Pathol 156:537–543.

    PubMed  CAS  Google Scholar 

  • Li CQ, Pignatelli B, Ohshima H (2000) Coexpression of interleukin-8 and inducible nitric oxide synthase in gastric mucosa infected with cagA+ Helicobacter pylori. Dig Dis Sci 45:55–62.

    PubMed  CAS  Google Scholar 

  • Lin WW and Karin M (2007) A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest 117:1175–1183.

    PubMed  CAS  Google Scholar 

  • Lind GE, Thorstensen L, Lovig T, Meling GI, Hamelin R, Rognum TO, Esteller M, Lothe RA (2004) A CpG island hypermethylation profile of primary colorectal carcinomas and colon cancer cell lines. Mol Cancer 3:28.

    PubMed  Google Scholar 

  • Ling XL, Fang DC, Wang RQ, Yang SM, Fang L (2004) Mitochondrial microsatellite instability in gastric cancer and its precancerous lesions. World J Gastroenterol 10:800–803.

    PubMed  CAS  Google Scholar 

  • Lipton L, Halford SE, Johnson V, Novelli MR, Jones A, Cummings C, Barclay E, Sieber O, Sadat A, Bisgaard ML, Hodgson SV, Aaltonen LA, Thomas HJ, Tomlinson IP (2003) Carcinogenesis in MYH-associated polyposis follows a distinct genetic pathway. Cancer Res 63:7595–7599.

    PubMed  CAS  Google Scholar 

  • Loftus EV, Jr. (2006) Epidemiology and risk factors for colorectal dysplasia and cancer in ulcerative colitis. Gastroenterol Clin North Am 35:517–531.

    PubMed  Google Scholar 

  • Losi L, Ponz de Leon M, Jiricny J, Di Gregorio C, Benatti P, Percesepe A, Fante R, Roncucci L, Pedroni M, Benhatter J (1997) K-ras and p53 mutations in hereditary non-polyposis colorectal cancers. Int J Cancer 74(1):94–96.

    Google Scholar 

  • Lund AH and van Lohuizen M (2004) Epigenetics and cancer. Genes Dev 18:2315–2335.

    PubMed  CAS  Google Scholar 

  • Lynch JP and Hoops TC (2002) The genetic pathogenesis of colorectal cancer. Hematol Oncol Clin North Am 16:1–36.

    Google Scholar 

  • Lynch JP and Lichtenstein GR (2004) Cyclooxygenase Activity in Gastrointestinal Cancer Development and Progression – Prospects as a Therapeutic Target. In: Morgan D, Fossman U, Nakaqda M (eds) Cancer and Inflammation. Birkhauser Verlag Basel, Basel, pp. 147–176.

    Google Scholar 

  • Lynch JP and Rustgi AK (2005) Mechanisms of GI Malignancies. In: Johnson LR, Barret KE, Gishan FK, Merchant JL, Said HM, Wood JD (eds) Physiology of the Gastrointestinal Tract, Fourth edn. Elsevier, San Diego, CA, pp. 477–498.

    Google Scholar 

  • Machado JC, Figueiredo C, Canedo P, Pharoah P, Carvalho R, Nabais S, Castro Alves C, Campos ML, Van Doorn LJ, Caldas C, Seruca R, Carneiro F, Sobrinho-Simoes M (2003) A proinflammatory genetic profile increases the risk for chronic atrophic gastritis and gastric carcinoma. Gastroenterology 125:364–371.

    PubMed  CAS  Google Scholar 

  • Malfertheiner P, Megraud F, O’Morain C, Bazzoli F, El-Omar E, Graham D, Hunt R, Rokkas T, Vakil N, Kuipers EJ (2007) Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report. Gut 56:772–781.

    PubMed  CAS  Google Scholar 

  • Marshall BJ (1995) Helicobacter pylori: the etiologic agent for peptic ulcer. JAMA 274:1064–1066.

    PubMed  CAS  Google Scholar 

  • Marshall BJ and Warren JR (1984) Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1:1311–1315.

    PubMed  CAS  Google Scholar 

  • Meek DW (2004) The p53 response to DNA damage. DNA Repair (Amst) 3:1049–1056.

    CAS  Google Scholar 

  • Mihara M, Yoshida Y, Tsukamoto T, Inada K, Nakanishi Y, Yagi Y, Imai K, Sugimura T, Tatematsu M, Ushijima T (2006) Methylation of multiple genes in gastric glands with intestinal metaplasia: A disorder with polyclonal origins. Am J Pathol 169:1643–1651.

    PubMed  CAS  Google Scholar 

  • Miyaki M, Iijima T, Kimura J, Yasuno M, Mori T, Hayashi Y, Koike M, Shitara N, Iwama T, Kuroki T (1999) Frequent mutation of beta-catenin and APC genes in primary colorectal tumors from patients with hereditary nonpolyposis colorectal cancer. Cancer Res 59:4506–4509.

    PubMed  CAS  Google Scholar 

  • Mocellin S, Wang E, Marincola FM (2001) Cytokines and immune response in the tumor microenvironment. J Immunother 24:392–407.

    CAS  Google Scholar 

  • Mocellin S, Rossi CR, Pilati P, Nitti D (2005) Tumor necrosis factor, cancer and anticancer therapy. Cytokine Growth Factor Rev 16:35–53.

    PubMed  CAS  Google Scholar 

  • Moss SF, Calam J, Agarwal B, Wang S, Holt PR (1996) Induction of gastric epithelial apoptosis by Helicobacter pylori. Gut 38:498–501.

    PubMed  CAS  Google Scholar 

  • Motoyama N and Naka K (2004) DNA damage tumor suppressor genes and genomic instability. Curr Opin Genet Dev 14:11–16.

    PubMed  CAS  Google Scholar 

  • Muller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, McClanahan T, Murphy E, Yuan W, Wagner SN, Barrera JL, Mohar A, Verastegui E, Zlotnik A (2001) Involvement of chemokine receptors in breast cancer metastasis. Nature 410:50–56.

    PubMed  CAS  Google Scholar 

  • Murakami T, Cardones AR, Hwang ST (2004) Chemokine receptors and melanoma metastasis. J Dermatol Sci 36:71–78.

    PubMed  CAS  Google Scholar 

  • Myeroff LL, Parsons R, Kim SJ, Hedrick L, Cho KR, Orth K, Mathis M, Kinzler KW, Lutterbaugh J, Park K, Bang Y-J, Lee HY, Park J-G, Lynch HT, Roberts AB, Vogeistein B, and Markowitz SD (1995) A transforming growth factor beta receptor type II gene mutation common in colon and gastric but rare in endometrial cancers with microsatellite instability. Cancer Res 55:5545–5547.

    PubMed  CAS  Google Scholar 

  • Nagy R, Sweet K, Eng C (2004) Highly penetrant hereditary cancer syndromes. Oncogene 23:6445–6470.

    PubMed  CAS  Google Scholar 

  • Nakatsuru S, Yanagisawa A, Furukawa Y, Ichii S, Kato Y, Nakamura Y, Horii A (1993) Somatic mutations of the APC gene in precancerous lesion of the stomach. Hum Mol Genet 2:1463–1465.

    PubMed  CAS  Google Scholar 

  • Nam JH and Murthy S (2004) Chronic inflammation and cancer in various organ systems. In: Cancer and Inflammation. Birkhauser Verlag Basel, Basel

    Google Scholar 

  • Nie Y, Liao J, Zhao X, Song Y, Yang GY, Wang LD, Yang CS (2002) Detection of multiple gene hypermethylation in the development of esophageal squamous cell carcinoma. Carcinogenesis 23:1713–1720.

    PubMed  CAS  Google Scholar 

  • Nomura A, Stemmermann GN, Chyou PH, Kato I, Perez GI, Blaser MJ (1991) Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii. N Engl J Med 325:1132–1136.

    PubMed  CAS  Google Scholar 

  • Ohnishi N, Yuasa H, Tanaka S, Sawa H, Miura M, Matsui A, Higashi H, Musashi M, Iwabuchi K, Suzuki M, Yamada G, Azuma T, Hatakeyama M (2008) Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse. Proc Natl Acad Sci U S A 105:1003–1008.

    PubMed  CAS  Google Scholar 

  • Ormandy CJ, Musgrove EA, Hui R, Daly RJ, Sutherland RL (2003) Cyclin D1, EMS1 and 11q13 amplification in breast cancer. Breast Cancer Res Treat 78:323–335.

    PubMed  CAS  Google Scholar 

  • Osborne J, Moore PS, Chang Y (1999) KSHV-encoded viral IL-6 activates multiple human IL-6 signaling pathways. Hum Immunol 60:921–927.

    PubMed  CAS  Google Scholar 

  • Ottini L, Palli D, Falchetti M, D'Amico C, Amorosi A, Saieva C, Calzolari A, Cimoli F, Tatarelli C, De Marchis L, Masala G, Mariani-Costantini R, Cama A (1997) Microsatellite instability in gastric cancer is associated with tumor location and family history in a high-risk population from Tuscany. Cancer Res 57:4523–4529.

    PubMed  CAS  Google Scholar 

  • Oue N, Matsumura S, Nakayama H, Kitadai Y, Taniyama K, Matsusaki K, Yasui W (2003) Reduced expression of the TSP1 gene and its association with promoter hypermethylation in gastric carcinoma. Oncology 64:423–429.

    PubMed  CAS  Google Scholar 

  • Pai R, Soreghan B, Szabo IL, Pavelka M, Baatar D, Tarnawski AS (2002) Prostaglandin E2 transactivates EGF receptor: a novel mechanism for promoting colon cancer growth and gastrointestinal hypertrophy. Nat Med 8:289–293.

    PubMed  CAS  Google Scholar 

  • Palli D, Caporaso NE, Shiao YH, Saieva C, Amorosi A, Masala G, Rice JM, Fraumeni JF, Jr. (1997) Diet, Helicobacter pylori, and p53 mutations in gastric cancer: a molecular epidemiology study in Italy. Cancer Epidemiol Biomarkers Prev 6:1065–1069.

    PubMed  CAS  Google Scholar 

  • Park TJ, Han SU, Cho YK, Paik WK, Kim YB, Lim IK (2001) Methylation of O(6)-methylguanine-DNA methyltransferase gene is associated significantly with K-ras mutation, lymph node invasion, tumor staging, and disease free survival in patients with gastric carcinoma. Cancer 92:2760–2768.

    PubMed  CAS  Google Scholar 

  • Parsonnet J, Friedman GD, Vandersteen DP, Chang Y, Vogelman JH, Orentreich N, Sibley RK (1991b) Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med 325:1127–1131.

    CAS  Google Scholar 

  • Parsonnet J, Friedman GD, Vandersteen DP, Chang Y, Vogelman JH, Orentreich N, Sibley RK (1991b) Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med 325:1127–1131.

    PubMed  CAS  Google Scholar 

  • Parsonnet J, Vandersteen D, Goates J, Sibley RK, Pritikin J, Chang Y (1991b) Helicobacter pylori infection in intestinal- and diffuse-type gastric adenocarcinomas. J Natl Cancer Inst 83:640–643.

    PubMed  CAS  Google Scholar 

  • Parsonnet J, Hansen S, Rodriguez L, Gelb AB, Warnke RA, Jellum E, Orentreich N, Vogelman JH, Friedman GD (1994) Helicobacter pylori infection and gastric lymphoma. N Engl J Med 330:1267–1271.

    PubMed  CAS  Google Scholar 

  • Parsons R, Myeroff LL, Liu B, Willson JK, Markowitz SD, Kinzler KW, Vogelstein B (1995) Microsatellite instability and mutations of the transforming growth factor beta type II receptor gene in colorectal cancer. Cancer Res 55:5548–5550.

    PubMed  CAS  Google Scholar 

  • Peek RM, Jr., Moss SF, Tham KT, Perez-Perez GI, Wang S, Miller GG, Atherton JC, Holt PR, Blaser MJ (1997) Helicobacter pylori cagA+ strains and dissociation of gastric epithelial cell proliferation from apoptosis [see comments]. J Natl Cancer Inst 89:863–868.

    PubMed  CAS  Google Scholar 

  • Peltomaki P (2001) Deficient DNA mismatch repair: a common etiologic factor for colon cancer. Hum Mol Genet 10:735–740.

    PubMed  CAS  Google Scholar 

  • Petronzelli F, Riccio A, Markham GD, Seeholzer SH, Stoerker J, Genuardi M, Yeung AT, Matsumoto Y, Bellacosa A (2000) Biphasic kinetics of the human DNA repair protein MED1 (MBD4), a mismatch-specific DNA N-glycosylase. J Biol Chem 275:32422–32429.

    PubMed  CAS  Google Scholar 

  • Phillips RK, Wallace MH, Lynch PM, Hawk E, Gordon GB, Saunders BP, Wakabayashi N, Shen Y, Zimmerman S, Godio L, Rodrigues-Bigas M, Su LK, Sherman J, Kelloff G, Levin B, Steinbach G (2002) A randomised, double blind, placebo controlled study of celecoxib, a selective cyclooxygenase 2 inhibitor, on duodenal polyposis in familial adenomatous polyposis. Gut 50:857–860.

    PubMed  CAS  Google Scholar 

  • Pidgeon GP, Lysaght J, Krishnamoorthy S, Reynolds JV, O'Byrne K, Nie D, Honn KV (2007) Lipoxygenase metabolism: roles in tumor progression and survival. Cancer Metastasis Rev 26:503–524.

    PubMed  CAS  Google Scholar 

  • Plentz RR, Wiemann SU, Flemming P, Meier PN, Kubicka S, Kreipe H, Manns MP, Rudolph KL (2003) Telomere shortening of epithelial cells characterises the adenoma-carcinoma transition of human colorectal cancer. Gut 52:1304–1307.

    PubMed  CAS  Google Scholar 

  • Plummer SM, Hall M, Faux SP (1995) Oxidation and genotoxicity of fecapentaene-12 are potentiated by prostaglandin H synthase. Carcinogenesis 16:1023–1028.

    PubMed  CAS  Google Scholar 

  • Prescott SM and White RL (1996) Self-promotion? Intimate connections between APC and prostaglandin H synthase-2. Cell 87:783–786.

    PubMed  CAS  Google Scholar 

  • Qian X, Huang C, Cho CH, Hui WM, Rashid A, Chan AO (2008) E-cadherin promoter hypermethylation induced by interleukin-1beta treatment or H. pylori infection in human gastric cancer cell lines. Cancer Lett 263:107–113.

    PubMed  CAS  Google Scholar 

  • Rampino N, Yamamoto H, Ionov Y, Li Y, Sawai H, Reed JC, Perucho M (1997) Somatic frameshift mutations in the BAX gene in colon cancers of the microsatellite mutator phenotype. Science 275:967–969.

    PubMed  CAS  Google Scholar 

  • Recavarren-Arce S, Leon-Barua R, Cok J, Berendson R, Gilman RH, Ramirez-Ramos A, Rodriguez C, Spira WM (1991) Helicobacter pylori and progressive gastric pathology that predisposes to gastric cancer. Scand J Gastroenterol Suppl 181:51–57.

    PubMed  CAS  Google Scholar 

  • Redston MS, Papadopoulos N, Caldas C, Kinzler KW, Kern SE (1995) Common occurrence of APC and K-ras gene mutations in the spectrum of colitis-associated neoplasias. Gastroenterology 108:383–392.

    PubMed  CAS  Google Scholar 

  • Riccio A, Aaltonen LA, Godwin AK, Loukola A, Percesepe A, Salovaara R, Masciullo V, Genuardi M, Paravatou-Petsotas M, Bassi DE, Ruggeri BA, Klein-Szanto AJ, Testa JR, Neri G, Bellacosa A (1999) The DNA repair gene MBD4 (MED1) is mutated in human carcinomas with microsatellite instability. Nat Genet 23:266–268.

    PubMed  CAS  Google Scholar 

  • Robinson K, Argent RH, Atherton JC (2007) The inflammatory and immune response to Helicobacter pylori infection. Best Pract Res Clin Gastroenterol 21:237–259.

    PubMed  CAS  Google Scholar 

  • Rose-John S, Scheller J, Elson G, Jones SA (2006) Interleukin-6 biology is coordinated by membrane-bound and soluble receptors: role in inflammation and cancer. J Leukoc Biol 80:227–236.

    PubMed  CAS  Google Scholar 

  • Rutter M, Saunders B, Wilkinson K, Rumbles S, Schofield G, Kamm M, Williams C, Price A, Talbot I, Forbes A (2004a) Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis. Gastroenterology 126:451–459.

    PubMed  Google Scholar 

  • Rutter MD, Saunders BP, Wilkinson KH, Rumbles S, Schofield G, Kamm MA, Williams CB, Price AB, Talbot IC, Forbes A (2004b) Cancer surveillance in longstanding ulcerative colitis: endoscopic appearances help predict cancer risk. Gut 53:1813–1816.

    PubMed  CAS  Google Scholar 

  • Samowitz WS, Holden JA, Curtin K, Edwards SL, Walker AR, Lin HA, Robertson MA, Nichols MF, Gruenthal KM, Lynch BJ, Leppert MF, Slattery ML (2001) Inverse relationship between microsatellite instability and K-ras and p53 gene alterations in colon cancer. Am J Pathol 158(4):1517–1524.

    Google Scholar 

  • Sampson JR, Dolwani S, Jones S, Eccles D, Ellis A, Evans DG, Frayling I, Jordan S, Maher ER, Mak T, Maynard J, Pigatto F, Shaw J, Cheadle JP (2003) Autosomal recessive colorectal adenomatous polyposis due to inherited mutations of MYH. Lancet 362:39–41.

    PubMed  CAS  Google Scholar 

  • Sancar A, Lindsey-Boltz LA, Unsal-Kacmaz K, Linn S (2004) Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu Rev Biochem 73:39–85.

    PubMed  CAS  Google Scholar 

  • Scotton CJ, Wilson JL, Milliken D, Stamp G, Balkwill FR (2001) Epithelial cancer cell migration: a role for chemokine receptors? Cancer Res 61:4961–4965.

    PubMed  CAS  Google Scholar 

  • Scotton CJ, Wilson JL, Scott K, Stamp G, Wilbanks GD, Fricker S, Bridger G, Balkwill FR (2002) Multiple actions of the chemokine CXCL12 on epithelial tumor cells in human ovarian cancer. Cancer Res 62:5930–5938.

    PubMed  CAS  Google Scholar 

  • Semba S, Yokozaki H, Yamamoto S, Yasui W, Tahara E (1996) Microsatellite instability in precancerous lesions and adenocarcinomas of the stomach. Cancer 77:1620–1627.

    PubMed  CAS  Google Scholar 

  • Sepulveda AR and Graham DY (2002) Role of Helicobacter pylori in gastric carcinogenesis. Gastroenterol Clin North Am 31:517–535, x.

    PubMed  Google Scholar 

  • Sepulveda AR, Santos AC, Yamaoka Y, Wu L, Gutierrez O, Kim JG, Graham DY (1999) Marked differences in the frequency of microsatellite instability in gastric cancer from different countries. Am J Gastroenterol 94:3034–3038.

    PubMed  CAS  Google Scholar 

  • Sepulveda AR, Wu L, Ota H, Gutierrez O, Kim JG, Genta RM, Graham DY (2000) Molecular identification of main cellular lineages as a tool for the classification of gastric cancer. Hum Pathol 31:566–574.

    PubMed  CAS  Google Scholar 

  • Sepulveda A, Peterson LE, Shelton J, Gutierrez O, Graham DY (2002) Histological patterns of gastritis in H. pylori-infected individuals with a family history of gastric cancer. Am J Gastroenterol 97:1365–1370.

    PubMed  CAS  Google Scholar 

  • Sharpless NE and DePinho RA (2004) Telomeres, stem cells, senescence, and cancer. J Clin Invest 113:160–168.

    PubMed  CAS  Google Scholar 

  • Shiao YH, Rugge M, Correa P, Lehmann HP, Scheer WD (1994) p53 alteration in gastric precancerous lesions. Am J Pathol 144:511–517.

    PubMed  CAS  Google Scholar 

  • Shibata Y, Haruki N, Kuwabara Y, Ishiguro H, Shinoda N, Sato A, Kimura M, Koyama H, Toyama T, Nishiwaki T, Kudo J, Terashita Y, Konishi S, Sugiura H, Fujii Y (2002) Chfr expression is downregulated by CpG island hypermethylation in esophageal cancer. Carcinogenesis 23:1695–1699.

    PubMed  CAS  Google Scholar 

  • Shimada T, Watanabe N, Hiraishi H, Terano A (1999) Redox regulation of interleukin-8 expression in MKN28 cells. Dig Dis Sci 44:266–273.

    PubMed  CAS  Google Scholar 

  • Shinmura K, Tani M, Isogaki J, Wang Y, Sugimura H, Yokota J (1998) RER phenotype and its associated mutations in familial gastric cancer. Carcinogenesis 19:247–251.

    PubMed  CAS  Google Scholar 

  • Shirin H, Sordillo EM, Kolevska TK, Hibshoosh H, Kawabata Y, Oh SH, Kuebler JF, Delohery T, Weghorst CM, Weinstein IB, Moss SF (2000) Chronic helicobacter pylori infection induces an apoptosis-resistant phenotype associated with decreased expression of p27(kip1). Infect Immun 68:5321–5328.

    PubMed  CAS  Google Scholar 

  • Sieber OM, Lipton L, Crabtree M, Heinimann K, Fidalgo P, Phillips RK, Bisgaard ML, Orntoft TF, Aaltonen LA, Hodgson SV, Thomas HJ, Tomlinson IP (2003) Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH. N Engl J Med 348:791–799.

    PubMed  Google Scholar 

  • Sipponen P and Marshall BJ (2000) Gastritis and gastric cancer. Western countries. Gastroenterol Clin North Am 29:579–592, v–vi.

    Google Scholar 

  • Sossenheimer MJ, Aston CE, Preston RA, Gates LK, Jr., Ulrich CD, Martin SP, Zhang Y, Gorry MC, Ehrlich GD, Whitcomb DC (1997) Clinical characteristics of hereditary pancreatitis in a large family, based on high-risk haplotype. The Midwest Multicenter Pancreatic Study Group (MMPSG). Am J Gastroenterol 92:1113–1116.

    PubMed  CAS  Google Scholar 

  • Souza RF, Appel R, Yin J, Wang S, Smolinski KN, Abraham JM, Zou TT, Shi YQ, Lei J, Cottrell J, Cymes K, Biden K, Simms L, Leggett B, Lynch PM, Frazier M, Powell SM, Harpaz N, Sugimura H, Young J, Meltzer SJ (1996) Microsatellite instability in the insulin-like growth factor II receptor gene in gastrointestinal tumours. Nat Genet 14:255–257.

    PubMed  CAS  Google Scholar 

  • Stenson WF (1995) Inflammatory Bowel Disease. In: Yamada T (ed) Textbook of Gastroenterology, Second edn. J.B. Lippincott Company, Philadelphia, pp. 1748–1805.

    Google Scholar 

  • Stenson WF (2007) Prostaglandins and epithelial response to injury. Curr Opin Gastroenterol 23:107–110.

    PubMed  CAS  Google Scholar 

  • Strathdee G (2002) Epigenetic versus genetic alterations in the inactivation of E-cadherin. Semin Cancer Biol 12:373–379.

    PubMed  CAS  Google Scholar 

  • Strickler JG, Zheng J, Shu Q, Burgart LJ, Alberts SR, Shibata D (1994) p53 mutations and microsatellite instability in sporadic gastric cancer: when guardians fail. Cancer Res 54:4750–4755.

    PubMed  CAS  Google Scholar 

  • Sunpaweravong P, Sunpaweravong S, Puttawibul P, Mitarnun W, Zeng C, Baron AE, Franklin W, Said S, Varella-Garcia M (2005) Epidermal growth factor receptor and cyclin D1 are independently amplified and overexpressed in esophageal squamous cell carcinoma. J Cancer Res Clin Oncol 131:111–119.

    PubMed  CAS  Google Scholar 

  • Suzuki H, Watkins DN, Jair KW, Schuebel KE, Markowitz SD, Dong Chen W, Pretlow TP, Yang B, Akiyama Y, Van Engeland M, Toyota M, Tokino T, Hinoda Y, Imai K, Herman JG, Baylin SB (2004) Epigenetic inactivation of SFRP genes allows constitutive WNT signaling in colorectal cancer. Nat Genet 36:417–422.

    PubMed  CAS  Google Scholar 

  • Suzuki N, Yasui M, Geacintov NE, Shafirovich V, Shibutani S (2005) Miscoding events during DNA synthesis past the nitration-damaged base 8-nitroguanine. Biochemistry 44:9238–9245.

    PubMed  CAS  Google Scholar 

  • Teich N, Rosendahl J, Toth M, Mossner J, Sahin-Toth M (2006) Mutations of human cationic trypsinogen (PRSS1) and chronic pancreatitis. Hum Mutat 27:721–730.

    PubMed  CAS  Google Scholar 

  • Thibodeau SN, Bren G, Schaid D (1993) Microsatellite instability in cancer of the proximal colon. Science 260:816–819.

    PubMed  CAS  Google Scholar 

  • To KF, Leung WK, Lee TL, Yu J, Tong JH, Chan MW, Ng EK, Chung SC, Sung JJ (2002) Promoter hypermethylation of tumor-related genes in gastric intestinal metaplasia of patients with and without gastric cancer. Int J Cancer 102:623–628.

    PubMed  CAS  Google Scholar 

  • Tomlinson I, Ilyas M, Johnson V, Davies A, Clark G, Talbot I, Bodmer W (1998) A comparison of the genetic pathways involved in the pathogenesis of three types of colorectal cancer. J Pathol 184:148–152.

    PubMed  CAS  Google Scholar 

  • Torres VJ, VanCompernolle SE, Sundrud MS, Unutmaz D, Cover TL (2007) Helicobacter pylori vacuolating cytotoxin inhibits activation-induced proliferation of human T and B lymphocyte subsets. J Immunol 179:5433–5440.

    PubMed  CAS  Google Scholar 

  • Toyota M, Ahuja N, Suzuki H, Itoh F, Ohe-Toyota M, Imai K, Baylin SB, Issa JP (1999) Aberrant methylation in gastric cancer associated with the CpG island methylator phenotype. Cancer Res 59:5438–5442.

    PubMed  CAS  Google Scholar 

  • Toyota M, Sasaki Y, Satoh A, Ogi K, Kikuchi T, Suzuki H, Mita H, Tanaka N, Itoh F, Issa JP, Jair KW, Schuebel KE, Imai K, Tokino T (2003) Epigenetic inactivation of CHFR in human tumors. Proc Natl Acad Sci U S A 100:7818–7823.

    PubMed  CAS  Google Scholar 

  • Ueki T, Toyota M, Sohn T, Yeo CJ, Issa JP, Hruban RH, Goggins M (2000) Hypermethylation of multiple genes in pancreatic adenocarcinoma. Cancer Res 60:1835–1839.

    PubMed  CAS  Google Scholar 

  • Ulrich CM, Bigler J, Potter JD (2006) Non-steroidal anti-inflammatory drugs for cancer prevention: promise, perils and pharmacogenetics. Nat Rev Cancer 6:130–140.

    PubMed  CAS  Google Scholar 

  • Umar A, Boland CR, Terdiman JP, Syngal S, de la Chapelle A, Ruschoff J, Fishel R, Lindor NM, Burgart LJ, Hamelin R, Hamilton SR, Hiatt RA, Jass J, Lindblom A, Lynch HT, Peltomaki P, Ramsey SD, Rodriguez-Bigas MA, Vasen HF, Hawk ET, Barrett JC, Freedman AN, Srivastava S (2004) Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 96:261–268.

    PubMed  CAS  Google Scholar 

  • Valko M, Morris H, Cronin MT (2005) Metals, toxicity and oxidative stress. Curr Med Chem 12:1161–1208.

    PubMed  CAS  Google Scholar 

  • Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M (2006) Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 160:1–40.

    PubMed  CAS  Google Scholar 

  • Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J (2007) Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 39:44–84.

    PubMed  CAS  Google Scholar 

  • Vasen HF, Watson P, Mecklin JP, Lynch HT (1999) New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. Gastroenterology 116:1453–1456.

    PubMed  CAS  Google Scholar 

  • Veigl ML, Kasturi L, Olechnowicz J, Ma AH, Lutterbaugh JD, Periyasamy S, Li GM, Drummond J, Modrich PL, Sedwick WD, Markowitz SD (1998) Biallelic inactivation of hMLH1 by epigenetic gene silencing, a novel mechanism causing human MSI cancers. Proc Natl Acad Sci U S A 95:8698–8702.

    PubMed  CAS  Google Scholar 

  • Verhulst ML, van Oijen AH, Roelofs HM, Peters WH, Jansen JB (2000) Antral glutathione concentration and glutathione S-transferase activity in patients with and without Helicobacter pylori. Dig Dis Sci 45:629–632.

    PubMed  CAS  Google Scholar 

  • Vivanco I and Sawyers CL (2002) The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer 2:489–501.

    PubMed  CAS  Google Scholar 

  • Waki T, Tamura G, Sato M, Terashima M, Nishizuka S, Motoyama T (2003) Promoter methylation status of DAP-kinase and RUNX3 genes in neoplastic and non-neoplastic gastric epithelia. Cancer Sci 94:360–364.

    PubMed  CAS  Google Scholar 

  • Walsh CP, Chaillet JR, Bestor TH (1998) Transcription of IAP endogenous retroviruses is constrained by cytosine methylation. Nat Genet 20:116–117.

    PubMed  CAS  Google Scholar 

  • Wang MT, Honn KV, Nie D (2007) Cyclooxygenases, prostanoids, and tumor progression. Cancer Metastasis Rev 26:525–534.

    PubMed  CAS  Google Scholar 

  • Warren JR and Marshall B (1983) Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet 1:1273–1275.

    Google Scholar 

  • Wendum D, Masliah J, Trugnan G, Flejou JF (2004) Cyclooxygenase-2 and its role in colorectal cancer development. Virchows Arch 445:327–333.

    PubMed  CAS  Google Scholar 

  • Whitcomb DC and Pogue-Geile K (2002) Pancreatitis as a risk for pancreatic cancer. Gastroenterol Clin North Am 31:663–678.

    PubMed  Google Scholar 

  • Whitcomb DC, Gorry MC, Preston RA, Furey W, Sossenheimer MJ, Ulrich CD, Martin SP, Gates LK, Jr., Amann ST, Toskes PP, Liddle R, McGrath K, Uomo G, Post JC, Ehrlich GD (1996) Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene. Nat Genet 14:141–145.

    PubMed  CAS  Google Scholar 

  • White ES, Strieter RM, Arenberg DA (2002) Chemokines as therapeutic targets in non-small cell lung cancer. Curr Med Chem Anti-Canc Agents 2:403–417.

    CAS  Google Scholar 

  • Wilson KT and Crabtree JE (2007) Immunology of Helicobacter pylori: insights into the failure of the immune response and perspectives on vaccine studies. Gastroenterology 133:288–308.

    PubMed  CAS  Google Scholar 

  • Wong BC, Lam SK, Wong WM, Chen JS, Zheng TT, Feng RE, Lai KC, Hu WH, Yuen ST, Leung SY, Fong DY, Ho J, Ching CK (2004) Helicobacter pylori eradication to prevent gastric cancer in a high-risk region of China: a randomized controlled trial. JAMA 291:187–194.

    PubMed  CAS  Google Scholar 

  • Wotherspoon AC, Ortiz-Hidalgo C, Falzon MR, Isaacson PG (1991) Helicobacter pylori-associated gastritis and primary B-cell gastric lymphoma. Lancet 338:1175–1176.

    PubMed  CAS  Google Scholar 

  • Wotherspoon AC, Doglioni C, Diss TC, Pan L, Moschini A, de Boni M, Isaacson PG (1993) Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori. Lancet 342:575–577.

    PubMed  CAS  Google Scholar 

  • Wu MS, Lee CW, Shun CT, Wang HP, Lee WJ, Sheu JC, Lin JT (1998) Clinicopathological significance of altered loci of replication error and microsatellite instability-associated mutations in gastric cancer. Cancer Res 58:1494–1497.

    PubMed  CAS  Google Scholar 

  • Wu MS, Lee CW, Shun CT, Wang HP, Lee WJ, Chang MC, Sheu JC, Lin JT (2000) Distinct clinicopathologic and genetic profiles in sporadic gastric cancer with different mutator phenotypes. Genes Chromosomes Cancer 27:403–411.

    PubMed  CAS  Google Scholar 

  • Xu XL, Yu J, Zhang HY, Sun MH, Gu J, Du X, Shi DR, Wang P, Yang ZH, Zhu JD (2004) Methylation profile of the promoter CpG islands of 31 genes that may contribute to colorectal carcinogenesis. World J Gastroenterol 10:3441–3454.

    PubMed  CAS  Google Scholar 

  • Yagi OK, Akiyama Y, Nomizu T, Iwama T, Endo M, Yuasa Y (1998) Proapoptotic gene BAX is frequently mutated in hereditary nonpolyposis colorectal cancers but not in adenomas. Gastroenterology 114:268–274.

    PubMed  CAS  Google Scholar 

  • Yamamoto H, Sawai H, Perucho M (1997) Frameshift somatic mutations in gastrointestinal cancer of the microsatellite mutator phenotype. Cancer Res 57:4420–4426.

    PubMed  CAS  Google Scholar 

  • Yamaoka Y, Kodama T, Kashima K, Graham DY, Sepulveda AR (1998) Variants of the 3' region of the cagA gene in Helicobacter pylori isolates from patients with different H. pylori-associated diseases. J Clin Microbiol 36:2258–2263.

    PubMed  CAS  Google Scholar 

  • Yang B, House MG, Guo M, Herman JG, Clark DP (2005) Promoter methylation profiles of tumor suppressor genes in intrahepatic and extrahepatic cholangiocarcinoma. Mod Pathol 18(3):412–420.

    Google Scholar 

  • Yang L and Carbone DP (2004) Tumor-host immune interactions and dendritic cell dysfunction. Adv Cancer Res 92:13–27.

    PubMed  CAS  Google Scholar 

  • Yao Y, Tao H, Park DI, Sepulveda JL, Sepulveda AR (2006) Demonstration and characterization of mutations induced by Helicobacter pylori organisms in gastric epithelial cells. Helicobacter 11:272–286.

    PubMed  CAS  Google Scholar 

  • Yermilov V, Rubio J, Becchi M, Friesen MD, Pignatelli B, Ohshima H (1995) Formation of 8-nitroguanine by the reaction of guanine with peroxynitrite in vitro. Carcinogenesis 16:2045–2050.

    PubMed  CAS  Google Scholar 

  • Yin J, Harpaz N, Tong Y, Huang Y, Laurin J, Greenwald BD, Hontanosas M, Newkirk C, Meltzer SJ (1993) p53 point mutations in dysplastic and cancerous ulcerative colitis lesions. Gastroenterology 104:1633–1639.

    PubMed  CAS  Google Scholar 

  • Yoder JA, Walsh CP, Bestor TH (1997) Cytosine methylation and the ecology of intragenomic parasites. Trends Genet 13:335–340.

    PubMed  CAS  Google Scholar 

  • Yoshitaka T, Matsubara N, Ikeda M, Tanino M, Hanafusa H, Tanaka N, Shimizu K (1996) Mutations of E2F-4 trinucleotide repeats in colorectal cancer with microsatellite instability. Biochem Biophys Res Commun 227:553–557.

    PubMed  CAS  Google Scholar 

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  1. Hospital of the University of Pennsylvania, Pennsylvania, PA, USA

    Antonia R. Sepulveda

  2. Division of Gastroenterology/650 CRB, 415 Curie Blvd., Philadelphia, PA, USA

    John P. Lynch

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    Andrei Thomas-Tikhonenko

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Sepulveda, A.R., Lynch, J.P. (2010). Genetic Instability and Chronic Inflammation in Gastrointestinal Cancers. In: Thomas-Tikhonenko, A. (eds) Cancer Genome and Tumor Microenvironment. Cancer Genetics. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0711-0_16

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