Cancer and inflammation: An old intuition with rapidly evolving new concepts

Annual Review of Immunology

Volumn 30, Issue , 2012, Pages 677-706

  Trinchieri, Giorgio ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

Author keywords

Colorectal cancer; DNA damage; Energy metabolism; Microbiota; Obesity

Indexed keywords

ACETYLSALICYLIC ACID; B RAF KINASE; CXCL1 CHEMOKINE; CXCL2 CHEMOKINE; CYCLOOXYGENASE 1; CYCLOOXYGENASE 2; CYCLOOXYGENASE 2 INHIBITOR; EPIDERMAL GROWTH FACTOR RECEPTOR 2; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 11; INTERLEUKIN 1BETA CONVERTING ENZYME; INTERLEUKIN 6; MITOGEN ACTIVATED PROTEIN KINASE; NITRIC OXIDE SYNTHASE; NONSTEROID ANTIINFLAMMATORY AGENT; PROSTAGLANDIN E2; PROTEIN MLH1; PROTEIN RET; PROTEIN TYROSINE KINASE; REACTIVE NITROGEN SPECIES; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; STAT3 PROTEIN; STRESS ACTIVATED PROTEIN KINASE; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 4; TRYPSINOGEN; VASCULOTROPIN;

ADAPTIVE IMMUNITY; ADIPOSE TISSUE; ANOREXIA; BLADDER CARCINOMA; BODY MASS; CACHEXIA; CANCER INCIDENCE; CANCER MORTALITY; CANCER SUSCEPTIBILITY; CARCINOGENESIS; CARDIOVASCULAR DISEASE; CELL AGING; CELL PROLIFERATION; CELL TRANSFORMATION; CEREBROVASCULAR DISEASE; CHRONIC INFLAMMATION; COLITIS; COLON CANCER; COLORECTAL CANCER; COMMENSAL; CROHN DISEASE; DIGESTIVE SYSTEM CANCER; DISEASE ASSOCIATION; DNA DAMAGE; DNA REPAIR; DOWN REGULATION; ENDOPLASMIC RETICULUM STRESS; ENERGY METABOLISM; ENTERITIS; ENZYME ACTIVATION; EPIGENETICS; GENE EXPRESSION; GENE MUTATION; GENE OVEREXPRESSION; GENE REARRANGEMENT; GENETIC ASSOCIATION; HELICOBACTER PYLORI; HOMEOSTASIS; HUMAN; IMMUNE RESPONSE; INDWELLING CATHETER; INFECTION; INFLAMMATION; INNATE IMMUNITY; INSULIN RESISTANCE; INTESTINE FLORA; LIVER CELL CARCINOMA; LUNG CANCER; MESOTHELIOMA; METABOLIC SYNDROME X; MULTIPLE MYELOMA; NEOPLASM; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHODGKIN LYMPHOMA; NONHUMAN; OBESITY; ONCOGENE; ONCOGENE K RAS; ONCOGENE MYC; ONCOGENE RAS; OXIDATIVE STRESS; PANCREAS CARCINOMA; PARACRINE SIGNALING; PHENOTYPE; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; RECTUM CANCER; REVIEW; SENESCENCE; SKIN CARCINOGENESIS; SYSTEMIC INFLAMMATORY RESPONSE SYNDROME; THYROID CARCINOMA; TISSUE INJURY; TUMOR MICROENVIRONMENT; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED PERIODIC SYNDROME; TUMOR PROMOTION; ULCERATIVE COLITIS; UPREGULATION; WART VIRUS; WNT SIGNALING PATHWAY;

ANIMALS; DISEASE SUSCEPTIBILITY; HUMANS; INFLAMMATION; NEOPLASMS;

EID: 84859401430     PISSN: 07320582     EISSN: 15453278     Source Type: Book Series    
DOI: 10.1146/annurev-immunol-020711-075008     Document Type: Review

References (189)

1. Hanahan D, Weinberg RA. 2000. The hallmarks of cancer. Cell 100:57-70
2. Hanahan D, Weinberg RA. 2011. Hallmarks of cancer: the next generation. Cell 144:646-74
3. Pierce GB, Speers WC. 1988. Tumors as caricatures of the process of tissue renewal: prospects for therapy by directing differentiation. Cancer Res. 48:1996-2004
4. Bissell MJ, Hines WC. 2011. Why don't we get more cancer? A proposed role of the microenvironment in restraining cancer progression. Nat. Med. 17:320-29
5. Dolberg DS, Hollingsworth R, Hertle M, Bissell MJ. 1985. Wounding and its role in RSV-mediated tumor formation. Science 230:676-78
6. Reedy J. 1975. Galen on cancer and related diseases. Clio Med. 10:227-38
7. Balkwill F, Mantovani A. 2001. Inflammation and cancer: back to Virchow? Lancet 357:539-45
8. Dvorak HF. 1986. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N. Engl. J. Med. 315:1650-59
9. Coussens LM, Werb Z. 2002. Inflammation and cancer. Nature 420:860-67
10. Schetter AJ, Heegaard NH, Harris CC. 2010. Inflammation and cancer: interweaving microRNA, free radical, cytokine and p53 pathways. Carcinogenesis 31:37-49
11. Johansson M, Denardo DG, Coussens LM. 2008. Polarized immune responses differentially regulate cancer development. Immunol. Rev. 222:145-54
12. Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A. 2009. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis 30:1073-81
13. Grivennikov SI, Greten FR, Karin M. 2010. Immunity, inflammation, and cancer. Cell 140:883-99
14. Vesely MD, Kershaw MH, Schreiber RD, Smyth MJ. 2011. Natural innate and adaptive immunity to cancer. Annu. Rev. Immunol. 29:235-71
15. Parkin DM. 2006. The global health burden of infection-associated cancers in the year 2002. Int. J. Cancer 118:3030-44
16. Pedersen N, Duricova D, Elkjaer M, Gamborg M, Munkholm P, Jess T. 2010. Risk of extra-intestinal cancer in inflammatory bowel disease: meta-analysis of population-based cohort studies. Am. J. Gastroenterol. 105:1480-87
17. Bernstein CN, Blanchard JF, Rawsthorne P, Yu N. 2001. The prevalence of extraintestinal diseases in inflammatory bowel disease: a population-based study. Am. J. Gastroenterol. 96:1116-22
18. Adami J, Gabel H, Lindelof B, Ekstrom K, Rydh B, et al. 2003. Cancer risk following organ transplantation: a nationwide cohort study in Sweden. Br. J. Cancer 89:1221-27
19. Wall BM, Dmochowski RR, Malecha M, Mangold T, Bobal MA, Cooke CR. 2001. Inducible nitric oxide synthase in the bladder of spinal cord injured patients with a chronic indwelling urinary catheter. J. Urol. 165:1457-61
20. Ameille J, Brochard P, Letourneux M, Paris C, Pairon JC. 2011. Asbestos-related cancer risk in patients with asbestosis or pleural plaques. Rev. Mal. Respir. 28:e11-17
21. Rebours V, Boutron-Ruault MC, Jooste V, Bouvier AM, Hammel P, et al. 2009. Mortality rate and risk factors in patients with hereditary pancreatitis: uni-and multidimensional analyses. Am. J. Gastroenterol. 104:2312-17
22. de Martel C, Franceschi S. 2009. Infections and cancer: established associations and new hypotheses. Crit. Rev. Oncol. Hematol. 70:183-94
23. Larsson SC, Wolk A. 2008. Excess body fatness: an important cause of most cancers. Lancet 371:536-37
24. Coebergh JW, Martin-Moreno JM, Soerjomataram I, Renehan AG. 2010. The long road towards cancer prevention: 4 steps backward and 8 forward. Eur. J. Cancer 46:2660-62
25. Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. 2008. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 371:569-78
26. Renehan AG, Soerjomataram I, Tyson M, Egger M, Zwahlen M, et al. 2010. Incident cancer burden attributable to excess body mass index in 30 European countries. Int. J. Cancer 126:692-702
27. Calle EE, RodriguezC, Walker-Thurmond K, ThunMJ. 2003. Overweight, obesity, andmortality from cancer in a prospectively studied cohort of US adults. N. Engl. J. Med. 348:1625-38
28. Donohoe CL, Doyle SL, Reynolds JV. 2011. Visceral adiposity, insulin resistance and cancer risk. Diabetol. Metab. Syndr. 3:12
29. Despres JP, Lemieux I. 2006. Abdominal obesity and metabolic syndrome. Nature 444:881-87
30. Renehan AG, Roberts DL, Dive C. 2008. Obesity and cancer: pathophysiological and biological mechanisms. Arch. Physiol. Biochem. 114:71-83
31. Hotamisligil GS. 2006. Inflammation and metabolic disorders. Nature 444:860-67
32. Gregor MF, Hotamisligil GS. 2011. Inflammatory mechanisms in obesity. Annu. Rev. Immunol. 29:415-45
33. Wellen KE, Thompson CB. 2010. Cellular metabolic stress: considering how cells respond to nutrient excess. Mol. Cell 40:323-32
34. Hotamisligil GS, Shargill NS, Spiegelman BM. 1993. Adipose expression of tumor necrosis factor-α: direct role in obesity-linked insulin resistance. Science 259:87-91
35. Ouchi N, Parker JL, Lugus JJ, Walsh K. 2011. Adipokines in inflammation and metabolic disease. Nat. Rev. Immunol. 11:85-97
36. Lumeng CN, Bodzin JL, Saltiel AR. 2007. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J. Clin. Investig. 117:175-84
37. Lumeng CN, DelProposto JB, Westcott DJ, Saltiel AR. 2008. Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes. Diabetes 57:3239-46
38. Feuerer M, Herrero L, Cipolletta D, Naaz A, Wong J, et al. 2009. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat. Med. 15:930-39
39. Engel A, Barton GM. 2010. Unfolding new roles for XBP1 in immunity. Nat. Immunol. 11:365-67
40. Hummasti S, Hotamisligil GS. 2010. Endoplasmic reticulum stress and inflammation in obesity and diabetes. Circ. Res. 107:579-91
41. Kamp DW, Shacter E, Weitzman SA. 2011. Chronic inflammation and cancer: the role of the mitochondria. Oncology 25:400-10, 13
42. Naik E, Dixit VM. 2011. Mitochondrial reactive oxygen species drive proinflammatory cytokine production. J. Exp. Med. 208:417-20
43. Vijay-Kumar M, Aitken JD, Carvalho FA, Cullender TC, Mwangi S, et al. 2010. Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science 328:228-31
44. Samuel BS, Shaito A, Motoike T, Rey FE, Backhed F, et al. 2008. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc. Natl. Acad. Sci. USA 105:16767-72
45. Backhed F, Manchester JK, Semenkovich CF, Gordon JI. 2007. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc. Natl. Acad. Sci. USA 104:979-84
46. Backhed F, DingH, Wang T, Hooper LV, Koh GY, et al. 2004. The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl. Acad. Sci. USA 101:15718-23
47. Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. 2006. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444:1027-31
48. Turnbaugh PJ, HamadyM, Yatsunenko T, Cantarel BL, Duncan A, et al. 2009. A core gut microbiome in obese and lean twins. Nature 457:480-84
49. Turnbaugh PJ, Ridaura VK, Faith JJ, Rey FE, Knight R, Gordon JI. 2009. The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci. Transl. Med. 1:6ra14
50. Turnbaugh PJ, Backhed F, Fulton L, Gordon JI. 2008. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe 3:213-23
51. Guerra C, Schuhmacher AJ, Canamero M, Grippo PJ, Verdaguer L, et al. 2007. Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice. Cancer Cell 11:291-302
52. Khasawneh J, Schulz MD, Walch A, Rozman J, Hrabe de Angelis M, et al. 2009. Inflammation and mitochondrial fatty acid beta-oxidation link obesity to early tumor promotion. Proc. Natl. Acad. Sci. USA 106:3354-59
53. Park EJ, Lee JH, Yu GY, HeG, Ali SR, et al. 2010. Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression. Cell 140:197-208
54. Donohoe CL, Ryan AM, Reynolds JV. 2011. Cancer cachexia: mechanisms and clinical implications. Gastroenterol. Res. Pract. 2011:601434
55. Lira FS, Rosa JC, Yamashita AS, Koyama CH, Batista ML Jr, Seelaender M. 2009. Endurance training induces depot-specific changes in IL-10/TNF- αratio in rat adipose tissue. Cytokine 45:80-85
56. Tan BH, Fearon KC. 2010. Cytokine gene polymorphisms and susceptibility to cachexia. Curr. Opin. Support Palliat. Care 4:243-48
57. Deans DA, Tan BH, Wigmore SJ, Ross JA, de Beaux AC, et al. 2009. The influence of systemic inflammation, dietary intake and stage of disease on rate of weight loss in patients with gastro-oesophageal cancer. Br. J. Cancer 100:63-69
58. Braun TP, MarksDL. 2010. Pathophysiology and treatment of inflammatory anorexia in chronic disease. J. Cachex. Sarcopenia Muscle 1:135-45
59. Ruud J, Backhed F, Engblom D, Blomqvist A. 2010. Deletion of the gene encoding MyD88 protects from anorexia in a mouse tumor model. Brain Behav. Immun. 24:554-57
60. Coquerel Q, Sinno MH, Boukhettala N, Cöeffier M, Terashi M, et al. 2012. Intestinal inflammation influences alpha-MSH reactive autoantibodies: relevance to food intake and body weight. Psychoneuroendocrinology 37:94-106
61. Armougom F, Henry M, Vialettes B, Raccah D, Raoult D. 2009. Monitoring bacterial community of human gut microbiota reveals an increase in Lactobacillus in obese patients and Methanogens in anorexic patients. PLo S ONE 4:e7125
62. Samuel BS, Hansen EE, Manchester JK, Coutinho PM, Henrissat B, et al. 2007. Genomic and metabolic adaptations of Methanobrevibacter smithii to the human gut. Proc. Natl. Acad. Sci. USA 104:10643-48
63. Wang D, Dubois RN. 2010. Eicosanoids and cancer. Nat. Rev. Cancer 10:181-93
64. McAdam BF, Catella-Lawson F, Mardini IA, Kapoor S, Lawson JA, FitzGerald GA. 1999. Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: the human pharmacology of a selective inhibitor of COX-2. Proc. Natl. Acad. Sci. USA 96:272-77
65. Konstantinopoulos PA, Lehmann DF. 2005. The cardiovascular toxicity of selective and nonselective cyclooxygenase inhibitors: comparisons, contrasts, and aspirin confounding. J. Clin. Pharmacol. 45:742-50
66. Eberhart CE, Coffey RJ, Radhika A, Giardiello FM, Ferrenbach S, DuBois RN. 1994. Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology 107:1183-88
67. Sinicrope FA, Lemoine M, Xi L, Lynch PM, Cleary KR, et al. 1999. Reduced expression of cyclooxygenase 2 proteins in hereditary nonpolyposis colorectal cancers relative to sporadic cancers. Gastroenterology 117:350-58
68. Sheehan KM, Sheahan K, O'Donoghue DP, MacSweeney F, Conroy RM, et al. 1999. The relationship between cyclooxygenase-2 expression and colorectal cancer. JAMA 282:1254-57
69. Oshima M, Dinchuk JE, Kargman SL, Oshima H, Hancock B, et al. 1996. Suppression of intestinal polyposis in ApcΔ716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell 87:803-9
70. Castellone MD, Teramoto H, Williams BO, Druey KM, Gutkind JS. 2005. Prostaglandin E2 promotes colon cancer cell growth through a Gs-axin-β-catenin signaling axis. Science 310:1504-10
71. Wang D, Buchanan FG, Wang H, Dey SK, DuBois RN. 2005. Prostaglandin E2 enhances intestinal adenoma growth via activation of the Ras-mitogen-activated protein kinase cascade. Cancer Res. 65:1822-29
72. Salcedo R, Zhang X, Young HA, Michael N, Wasserman K, et al. 2003. Angiogenic effects of prostaglandin E2 are mediated by up-regulation of CXCR4 on human microvascular endothelial cells. Blood 102:1966-77
73. Pai R, Szabo IL, Soreghan BA, Atay S, Kawanaka H, Tarnawski AS. 2001. PGE(2) stimulates VEGF expression in endothelial cells viaERK2/JNK1 signaling pathways. Biochem. Biophys. Res. Commun. 286:923-28
74. Sheibanie AF, Yen JH, Khayrullina T, Emig F, Zhang M, et al. 2007. The proinflammatory effect of prostaglandin E2 in experimental inflammatory bowel disease is mediated through the IL-23->IL-17 axis. J. Immunol. 178:8138-47
75. Arber N, Eagle CJ, Spicak J, Racz I, Dite P, et al. 2006. Celecoxib for the prevention of colorectal adenomatous polyps. N. Engl. J. Med. 355:885-95
76. Bertagnolli MM, Eagle CJ, Zauber AG, RedstonM, Solomon SD, et al. 2006. Celecoxib for the prevention of sporadic colorectal adenomas. N. Engl. J. Med. 355:873-84
77. Rostom A, Dube C, LewinG, Tsertsvadze A, Barrowman N, et al. 2007. Nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors for primary prevention of colorectal cancer: a systematic review prepared for the US Preventive Services Task Force. Ann. Intern. Med. 146:376-89
78. Menter DG, Schilsky RL, DuBois RN. 2010. Cyclooxygenase-2 and cancer treatment: understanding the risk should be worth the reward. Clin. Cancer Res. 16:1384-90
79. Bertagnolli MM, Eagle CJ, Zauber AG, RedstonM, Breazna A, et al. 2009. Five-year efficacy and safety analysis of the Adenoma Prevention with Celecoxib Trial. Cancer Prev. Res. 2:310-21
80. Rothwell PM, Fowkes FG, Belch JF, Ogawa H, Warlow CP, Meade TW. 2011. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet 377:31-41
81. Williams CS, Watson AJ, Sheng H, Helou R, Shao J, DuBois RN. 2000. Celecoxib prevents tumor growth in vivo without toxicity to normal gut: lack of correlation between in vitro and in vivo models. Cancer Res. 60:6045-51
82. Matzinger P. 2007. Friendly and dangerous signals: is the tissue in control Nat. Immunol. 8:11-13
83. Allavena P, Garlanda C, Borrello MG, Sica A, Mantovani A. 2008. Pathways connecting inflammation and cancer. Curr. Opin. Genet. Dev. 18:3-10
84. Addadi Y, Moskovits N, Granot D, Lozano G, Carmi Y, et al. 2010. p53 status in stromal fibroblasts modulates tumor growth in an SDF1-dependent manner. Cancer Res. 70:9650-58
85. Herbert BS, Chanoux RA, Liu Y, Baenziger PH, Goswami CP, et al. 2010. A molecular signature of normal breast epithelial and stromal cells from Li-Fraumeni syndrome mutation carriers. Oncotarget 1:405-22
86. Hussain SP, Amstad P, Raja K, Ambs S, Nagashima M, et al. 2000. Increased p53 mutation load in noncancerous colon tissue from ulcerative colitis: a cancer-prone chronic inflammatory disease. Cancer Res. 60:3333-37
87. Chen N, Ma WY, She QB, Wu E, Liu G, et al. 2001. Transactivation of the epidermal growth factor receptor is involved in 12-O-tetradecanoylphorbol-13- acetate-induced signal transduction. J. Biol. Chem. 276:46722-28
88. Rundhaug JE, Fischer SM. 2010. Molecular mechanisms of mouse skin tumor promotion. Cancers 2:436-82
89. Matzinger P, Kamala T. 2011. Tissue-based class control: the other side of tolerance. Nat. Rev. Immunol. 11:221-30
90. Schreiber RD, Old LJ, Smyth MJ. 2011. Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science 331:1565-70
91. Zitvogel L, Apetoh L, Ghiringhelli F, Andre F, Tesniere A, Kroemer G. 2008. The anticancer immune response: indispensable for therapeutic success? J. Clin. Investig. 118:1991-2001
92. Bindea G, Mlecnik B, Fridman WH, Galon J. 2011. The prognostic impact of anti-cancer immune response: a novel classification of cancer patients. Semin. Immunopathol. 33:335-40
93. Bowcock AM. 2010. Genome-wide association studies and infectious disease. Crit. Rev. Immunol. 30:305-9
94. Vannberg FO, Chapman SJ, Hill AV. 2011. Human genetic susceptibility to intracellular pathogens. Immunol. Rev. 240:105-16
95. Lee JC, Parkes M. 2011. Genome-wide association studies and Crohn's disease. Brief Funct. Genomics 10:71-76
96. BolandCR. 2010. Chronic inflammation, colorectal cancer and gene polymorphisms. Dig. Dis. 28:590-95
97. Martin B, Ji S, Maudsley S, Mattson MP. 2010. "Control" laboratory rodents are metabolically morbid: why it matters. Proc. Natl. Acad. Sci. USA 107:6127-33
98. Lira FS, Rosa JC, Pimentel GD, Souza HA, Caperuto EC, et al. 2010. Endotoxin levels correlate positively with a sedentary lifestyle and negatively with highly trained subjects. Lipids Health Dis. 9:82
99. Takeuchi O, Akira S. 2010. Pattern recognition receptors and inflammation. Cell 140:805-20
100. Marichal T, Ohata K, Bedoret D, Mesnil C, Sabatel C, et al. 2011. DNA released from dying host cells mediates aluminum adjuvant activity. Nat. Med. 17:996-1002
101. Barbalat R, Ewald SE, Mouchess ML, BartonGM. 2011. Nucleic acid recognition by the innate immune system. Annu. Rev. Immunol. 29:185-214
102. Borrello MG, Degl'Innocenti D, Pierotti MA. 2008. Inflammation and cancer: the oncogene-driven connection. Cancer Lett. 267:262-70
103. Liu J, Yang G, Thompson-Lanza JA, Glassman A, Hayes K, et al. 2004. A genetically defined model for human ovarian cancer. Cancer Res. 64:1655-63
104. Ancrile B, Lim KH, Counter CM. 2007. Oncogenic Ras-induced secretion of IL6 is required for tumorigenesis. Genes Dev. 21:1714-19
105. Sparmann A, Bar-SagiD. 2004. Ras-induced interleukin-8 expression plays a critical role in tumor growth and angiogenesis. Cancer Cell 6:447-58
106. Wislez M, Fujimoto N, Izzo JG, Hanna AE, Cody DD, et al. 2006. High expression of ligands for chemokine receptor CXCR2 in alveolar epithelial neoplasia induced by oncogenic kras. Cancer Res. 66:4198-207
107. Yuspa SH. 1998. The pathogenesis of squamous cell cancer: lessons learned from studies of skin carcinogenesis. J. Dermatol. Sci. 17:1-7
108. Cataisson C, Ohman R, Patel G, Pearson A, Tsien M, et al. 2009. Inducible cutaneous inflammation reveals a protumorigenic role for keratinocyte CXCR2 in skin carcinogenesis. Cancer Res. 69:319-28
109. Cataisson C, Pearson AJ, TsienMZ, Mascia F, Gao JL, et al. 2006. CXCR2 ligands and G-CSF mediate PKCα-induced intraepidermal inflammation. J. Clin. Investig. 116:2757-66
110. Mascia F, Cataisson C, Lee TC, Threadgill D, Mariani V, et al. 2010. EGFR regulates the expression of keratinocyte-derived granulocyte/macrophage colony-stimulating factor in vitro and in vivo. J. Investig. Dermatol. 130:682-93
111. Liang S, Sharma A, Peng HH, Robertson G, Dong C. 2007. Targeting mutant (V600E) B-Raf in melanoma interrupts immunoediting of leukocyte functions and melanoma extravasation. Cancer Res. 67:5814-20
112. Shchors K, Shchors E, Rostker F, Lawlor ER, Brown-Swigart L, Evan GI. 2006. The Myc-dependent angiogenic switch in tumors is mediated by interleukin 1β. Genes Dev. 20:2527-38
113. Soucek L, Lawlor ER, Soto D, Shchors K, Swigart LB, Evan GI. 2007. Mast cells are required for angiogenesis and macroscopic expansion of Myc-induced pancreatic islet tumors. Nat. Med. 13:1211-18
114. Borrello MG, Alberti L, Fischer A, Degl'innocenti D, Ferrario C, et al. 2005. Induction of a proinflammatory program in normal human thyrocytes by the RET/PTC1 oncogene. Proc. Natl. Acad. Sci. USA 102:14825-30
115. Melillo RM, Castellone MD, Guarino V, De Falco V, Cirafici AM, et al. 2005. The RET/PTC-RASBRAF linear signaling cascade mediates the motile and mitogenic phenotype of thyroid cancer cells. J. Clin. Investig. 115:1068-81
116. Iliopoulos D, Hirsch HA, Struhl K. 2009. An epigenetic switch involving NF-κB, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation. Cell 139:693-706
117. Iliopoulos D, Jaeger SA, Hirsch HA, BulykML, Struhl K. 2010. STAT3 activation of miR-21 and miR-181b-1 via PTEN and CYLD are part of the epigenetic switch linking inflammation to cancer. Mol. Cell 39:493-506
118. Hartman ZC, Yang XY, Glass O, Lei G, Osada T, et al. 2011. HER2 overexpression elicits a proinflammatory IL-6 autocrine signaling loop that is critical for tumorigenesis. Cancer Res. 71:4380-91
119. Costinean S, Zanesi N, Pekarsky Y, Tili E, Volinia S, et al. 2006. Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in E(mu)-miR155 transgenic mice. Proc. Natl. Acad. Sci. USA 103:7024-29
120. Tili E, Michaille JJ, Wernicke D, Alder H, Costinean S, et al. 2011. Mutator activity induced by microRNA-155 (miR-155) links inflammation and cancer. Proc. Natl. Acad. Sci. USA 108:4908-13
121. Campisi J. 2011. Cellular senescence: putting the paradoxes in perspective. Curr. Opin. Genet. Dev. 21:107-12
122. Rodier F, Mũ noz DP, Teachenor R, Chu V, Le O, et al. 2011. DNA-SCARS: distinct nuclear structures that sustain damage-induced senescence growth arrest and inflammatory cytokine secretion. J. Cell Sci. 124:68-81
123. Rodier F, Copṕe JP, Patil CK, Hoeijmakers WA, Mũ noz DP, et al. 2009. Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion. Nat. Cell Biol. 11:973-79
124. Orjalo AV, Bhaumik D, Gengler BK, Scott GK, Campisi J. 2009. Cell surface-bound IL-1α is an upstream regulator of the senescence-associated IL-6/IL-8 cytokine network. Proc. Natl. Acad. Sci. USA 106:17031-36
125. Kuilman T, Michaloglou C, Vredeveld LC, Douma S, van Doorn R, et al. 2008. Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network. Cell 133:1019-31
126. Sharpless NE, DePinho RA. 2005. Cancer: crime and punishment. Nature 436:636-37
127. Halazonetis TD, Gorgoulis VG, Bartek J. 2008. An oncogene-induced DNA damage model for cancer development. Science 319:1352-55
128. Guerra C, ColladoM, Navas C, Schuhmacher AJ, Herńandez-Porras I, et al. 2011. Pancreatitis-induced inflammation contributes to pancreatic cancer by inhibiting oncogene-induced senescence. Cancer Cell 19:728-39
129. Barbie DA, Tamayo P, Boehm JS, Kim SY, Moody SE, et al. 2009. Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1. Nature 462:108-12
130. LiuF, Wu S, Ren H, GuJ. 2011. Klotho suppressesRIG-I-mediated senescence-associated inflammation. Nat. Cell Biol. 13:254-62
131. Ralph SJ, Rodríguez-Enríquez S, Neuzil J, Saavedra E, Moreno-Śanchez R. 2010. The causes of cancer revisited: "mitochondrial malignancy" and ROS-induced oncogenic transformation-whymitochondria are targets for cancer therapy. Mol. Aspects Med. 31:145-70
132. KC S, Ćarcamo JM, Golde DW. 2006. Antioxidants prevent oxidative DNA damage and cellular transformation elicited by the over-expression of c-MYC. Mutat. Res. 593:64-79
133. Weinberg F, Hamanaka R, WheatonWW, Weinberg S, Joseph J, et al. 2010. Mitochondrial metabolism and ROS generation are essential forKras-mediated tumorigenicity. Proc. Natl. Acad. Sci. USA 107:8788-93
134. Yoon JC, Ng A, Kim BH, Bianco A, Xavier RJ, Elledge SJ. 2010. Wnt signaling regulates mitochondrial physiology and insulin sensitivity. Genes Dev. 24:1507-18
135. Rabiet MJ, Huet E, Boulay F. 2005. Human mitochondria-derived N-formylated peptides are novel agonists equally active on FPR and FPRL1, while Listeria monocytogenes-derived peptides preferentially activate FPR. Eur. J. Immunol. 35:2486-95
136. Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, et al. 2010. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature 464:104-7
137. Iyer SS, Pulskens WP, Sadler JJ, Butter LM, Teske GJ, et al. 2009. Necrotic cells trigger a sterile inflammatory response through the Nlrp3 inflammasome. Proc. Natl. Acad. Sci. USA 106:20388-93
138. Zhou R, Yazdi AS, Menu P, Tschopp J. 2011. A role for mitochondria in NLRP3 inflammasome activation. Nature 469:221-25
139. Nakahira K, Haspel JA, Rathinam VA, Lee SJ, Dolinay T, et al. 2011. Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nat. Immunol. 12:222-30
140. Bulua AC, Simon A, Maddipati R, Pelletier M, Park H, et al. 2011. Mitochondrial reactive oxygen species promote production of proinflammatory cytokines and are elevated in TNFR1-associated periodic syndrome (TRAPS). J. Exp. Med. 208:519-33
141. Vandanmagsar B, Youm YH, Ravussin A, Galgani JE, Stadler K, et al. 2011. TheNLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat. Med. 17:179-88
142. Hussain SP, Harris CC. 2007. Inflammation and cancer: an ancient link with novel potentials. Int. J. Cancer 121:2373-80
143. Hakem R. 2008. DNA-damage repair: the good, the bad, and the ugly. EMBO J. 27:589-605
144. Dong CX, Deng DJ, Pan KF, Zhang L, Zhang Y, et al. 2009. Promoter methylation of p16 associated with Helicobacter pylori infection in precancerous gastric lesions: a population-based study. Int. J. Cancer 124:434-39
145. Das PM, Singal R. 2004. DNA methylation and cancer. J. Clin. Oncol. 22:4632-42
146. Fleisher AS, Esteller M, Harpaz N, Leytin A, Rashid A, et al. 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. 60:4864-68
147. Endo Y, Marusawa H, Kou T, Nakase H, Fujii S, et al. 2008. Activation-induced cytidine deaminase links between inflammation and the development of colitis-associated colorectal cancers. Gastroenterology 135:889-98. e3
148. Koblish HK, Hunter CA, Wysocka M, Trinchieri G, Lee WM. 1998. Immune suppression by recombinant interleukin (rIL)-12 involves interferon γ induction of nitric oxide synthase 2 (iNOS) activity: inhibitors ofNOgeneration reveal the extent of rIL-12 vaccine adjuvant effect. J. Exp. Med. 188:1603-10
149. Karin M, Greten FR. 2005. NF-κB: linking inflammation and immunity to cancer development and progression. Nat. Rev. Immunol. 5:749-59
150. Ben-Neriah Y, Karin M. 2011. Inflammation meets cancer, with NF-κB as the matchmaker. Nat. Immunol. 12:715-23
151. El Kasmi KC, Smith AM, Williams L, Neale G, Panopoulos AD, et al. 2007. Cutting edge: A transcriptional repressor and corepressor induced by the STAT3-regulated anti-inflammatory signaling pathway. J. Immunol. 179:7215-19
152. Yu H, Kortylewski M, Pardoll D. 2007. Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nat. Rev. Immunol. 7:41-51
153. Kamangar F, Dores GM, Anderson WF. 2006. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J. Clin. Oncol. 24:2137-50
154. Tomatis L, ed. 1990. Cancer, Causes, Occurrence and Control. Lyon: IARC Press
155. WCRF/AICR. 2007. Expert Report, Food, Nutrition, Physical Activity and the Prevention of Cancer: A Global Perspective. Washington, DC: Am. Inst. Cancer Res.
156. Apidianakis Y, Pitsouli C, PerrimonN, Rahme L. 2009. Synergy between bacterial infection and genetic predisposition in intestinal dysplasia. Proc. Natl. Acad. Sci. USA 106:20883-88
157. Cordero JB, Macagno JP, Stefanatos RK, Strathdee KE, Cagan RL, Vidal M. 2010. Oncogenic Ras diverts a host TNF tumor suppressor activity into tumor promoter. Dev. Cell 18:999-1011
158. Terzíc J, Grivennikov S, Karin E, Karin M. 2010. Inflammation and colon cancer. Gastroenterology 138:2101-14. e5
159. Saleh M, Trinchieri G. 2011. Innate immune mechanisms of colitis and colitis-associated colorectal cancer. Nat. Rev. Immunol. 11:9-20
160. Uronis JM, Muhlbauer M, Herfarth HH, Rubinas TC, Jones GS, Jobin C. 2009. Modulation of the intestinal microbiota alters colitis-associated colorectal cancer susceptibility. PLo S ONE 4:e6026
161. Vannucci L, Stepankova R, Kozakova H, Fiserova A, Rossmann P, Tlaskalova-Hogenova H. 2008. Colorectal carcinogenesis in germ-free and conventionally reared rats: different intestinal environments affect the systemic immunity. Int. J. Oncol. 32:609-17
162. Yang L, Pei Z. 2006. Bacteria, inflammation, and colon cancer. World J. Gastroenterol. 12:6741-46
163. Maddocks OD, Short AJ, Donnenberg MS, Bader S, Harrison DJ. 2009. Attaching and effacing Escherichia coli downregulate DNA mismatch repair protein in vitro and are associated with colorectal adenocarcinomas in humans. PLo S ONE 4:e5517
164. Wu S, Rhee KJ, Albesiano E, Rabizadeh S, Wu X, et al. 2009. A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat. Med. 15:1016-22
165. Sears CL. 2009. Enterotoxigenic Bacteroides fragilis: a rogue among symbiotes. Clin. Microbiol. Rev. 22:349-69
166. Garrett WS, Punit S, Gallini CA, MichaudM, Zhang D, et al. 2009. Colitis-associated colorectal cancer driven by T-bet deficiency in dendritic cells. Cancer Cell 16:208-19
167. Garrett WS, Gallini CA, Yatsunenko T, Michaud M, DuBois A, et al. 2010. Enterobacteriaceae act in concert with the gut microbiota to induce spontaneous and maternally transmitted colitis. Cell Host Microbe 8:292-300
168. Rakoff-Nahoum S, Medzhitov R. 2007. Regulation of spontaneous intestinal tumorigenesis through the adaptor protein MyD88. Science 317:124-27
169. Salcedo R, WorschechA, CardoneM, Jones Y, Gyulai Z, et al. 2010. MyD88-mediated signaling prevents development of adenocarcinomas of the colon: role of interleukin 18. J. Exp. Med. 207:1625-36
170. Allen IC, TeKippe EM, Woodford RM, Uronis JM, Holl EK, et al. 2010. The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer. J. Exp. Med. 207:1045-56
171. Elinav E, Strowig T, Kau AL, Henao-Mejia J, Thaiss CA, et al. 2011. NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell 145:745-57
172. JiangW, Lederman MM, Hunt P, Sieg SF, HaleyK, et al. 2009. Plasma levels of bacterialDNAcorrelate with immune activation and the magnitude of immune restoration in persons with antiretroviral-treated HIV infection. J. Infect. Dis. 199:1177-85
173. Brenchley JM, Price DA, Schacker TW, Asher TE, Silvestri G, et al. 2006. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat. Med. 12:1365-71
174. Jedrychowski W, Perera F, Maugeri U, Mroz E, Flak E, et al. 2011. Wheezing and asthma may be enhanced by broad spectrum antibiotics used in early childhood. Concept and results of a pharmacoepidemiology study. J. Physiol. Pharmacol. 62:189-95
175. Bercik P, Denou E, Collins J, JacksonW, Lu J, et al. 2011. The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology 141:599-609
176. Collins SM, Bercik P. 2009. The relationship between intestinal microbiota and the central nervous system in normal gastrointestinal function and disease. Gastroenterology 136:2003-14
177. Ochoa-Reṕaraz J, Mielcarz DW, Ditrio LE, Burroughs AR, Foureau DM, et al. 2009. Role of gut commensal microflora in the development of experimental autoimmune encephalomyelitis. J. Immunol. 183:6041-50
178. Brandon JA, Jennings CD, Kaplan AM, Bryson JS. 2011. Murine syngeneic graft-versus-host disease is responsive to broad-spectrum antibiotic therapy. J. Immunol. 186:3726-34
179. Wen L, Ley RE, Volchkov PY, Stranges PB, Avanesyan L, et al. 2008. Innate immunity and intestinal microbiota in the development of Type 1 diabetes. Nature 455:1109-13
180. WuHJ, Ivanov II, Darce J, Hattori K, Shima T, et al. 2010. Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity 32:815-27
181. Ivanov II, Atarashi K, Manel N, Brodie EL, Shima T. 2009. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139:485
182. Ichinohe T, Pang IK, Kumamoto Y, Peaper DR, Ho JH, et al. 2011. Microbiota regulates immune defense against respiratory tract influenza A virus infection. Proc. Natl. Acad. Sci. USA 108:5354-59
183. Fox JG, Feng Y, Theve EJ, Raczynski AR, Fiala JL, et al. 2010. Gut microbes define liver cancer risk in mice exposed to chemical and viral transgenic hepatocarcinogens. Gut 59:88-97
184. Rao VP, Poutahidis T, Ge Z, Nambiar PR, Boussahmain C, et al. 2006. Innate immune inflammatory response against enteric bacteria Helicobacter hepaticus induces mammary adenocarcinoma inmice. Cancer Res. 66:7395-400
185. Rossini A, Rumio C, Sfondrini L, Tagliabue E, Morelli D, et al. 2006. Influence of antibiotic treatment on breast carcinoma development in proto-neu transgenic mice. Cancer Res. 66:6219-24
186. Ness RB, Cauley JA. 2004. Antibiotics and breast cancer-what's the meaning of this? JAMA 291:880-81
187. Westbrook AM, Wei B, Braun J, Schiestl RH. 2009. Intestinal mucosal inflammation leads to systemic genotoxicity in mice. Cancer Res. 69:4827-34
188. Westbrook AM, Wei B, Braun J, Schiestl RH. 2011. Intestinal inflammation induces genotoxicity to extraintestinal tissues and cell types in mice. Int. J. Cancer 129:1815-25
189. Redon CE, Dickey JS, Nakamura AJ, Kareva IG, Naf D, et al. 2010. Tumors induce complex DNA damage in distant proliferative tissues in vivo. Proc. Natl. Acad. Sci. USA 107:17992-97