1932

Abstract

High-quality evidence indicates that regular use of aspirin is effective in reducing the risk for precancerous colorectal neoplasia and colorectal cancer (CRC). This has led to US and international guidelines recommending aspirin for the primary prevention of CRC in specific populations. In this review, we summarize key questions that require addressing prior to broader adoption of aspirin-based chemoprevention, review recent evidence related to the benefits and harms of aspirin use among specific populations, and offer a rationale for precision prevention approaches. We specifically consider the mechanistic implications of evidence showing differences in aspirin's effects according to age, the potential role of modifiable mechanistic biomarkers for personalizing prevention, and emerging evidence that the gut microbiota may offer novel aspirin-associated preventive targets to reduce high-risk neoplasia.

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2021-01-27
2024-06-13
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Literature Cited

  1. 1. 
    Chan AT, Arber N, Burn J et al. 2012. Aspirin in the chemoprevention of colorectal neoplasia: an overview. Cancer Prev. Res. 5:164–78
    [Google Scholar]
  2. 2. 
    Nishihara R, Lochhead P, Kuchiba A et al. 2013. Aspirin use and risk of colorectal cancer according to BRAF mutation status. JAMA 309:2563–71
    [Google Scholar]
  3. 3. 
    Sutcliffe P, Connock M, Gurung T et al. 2013. Aspirin for prophylactic use in the primary prevention of cardiovascular disease and cancer: a systematic review and overview of reviews. Health Technol. Assess. 17:1–253
    [Google Scholar]
  4. 4. 
    Chan AT, McNeil J. 2018. Aspirin and cancer prevention in the elderly: Where do we go from here. Gastroenterology 156:534–38
    [Google Scholar]
  5. 5. 
    Bibbins-Domingo K. 2016. Aspirin use for the primary prevention of cardiovascular disease and colorectal cancer: U.S. Preventive Services Task Force recommendation statement. Ann. Intern. Med. 164:836–45
    [Google Scholar]
  6. 6. 
    McNeil JJ, Nelson MR, Woods RL et al. 2018. Effect of aspirin on all-cause mortality in the healthy elderly. N. Engl. J. Med. 379:1519–28
    [Google Scholar]
  7. 7. 
    Katona BW, Weiss JM. 2020. Chemoprevention of colorectal cancer. Gastroenterology 158:368–88
    [Google Scholar]
  8. 8. 
    Thun MJ, Jacobs EJ, Patrono C 2012. The role of aspirin in cancer prevention. Nat. Rev. Clin. Oncol. 9:259–67
    [Google Scholar]
  9. 9. 
    Dube C, Rostom A, Lewin G et al. 2007. The use of aspirin for primary prevention of colorectal cancer: a systematic review prepared for the U.S. Preventive Services Task Force. Ann. Intern. Med. 146:365–75
    [Google Scholar]
  10. 10. 
    Cole BF, Logan RF, Halabi S et al. 2009. Aspirin for the chemoprevention of colorectal adenomas: meta-analysis of the randomized trials. J. Natl. Cancer Inst. 101:256–66
    [Google Scholar]
  11. 11. 
    Chubak J, Kamineni A, Buist DSM et al. 2015. Aspirin Use for the Prevention of Colorectal Cancer: An Updated Systematic Evidence Review for the U.S. Preventive Services Task Force Evidence Synthesis No. 133, Rep. No. 15-05228-EF-1 Rockville, MD: Agency Healthc. Res. Quality
    [Google Scholar]
  12. 12. 
    Giovannucci E, Rimm EB, Stampfer MJ et al. 1994. Aspirin use and the risk for colorectal cancer and adenoma in male health professionals. Ann. Intern. Med. 121:241–46
    [Google Scholar]
  13. 13. 
    Chan AT, Giovannucci EL, Meyerhardt JA et al. 2005. Long-term use of aspirin and nonsteroidal anti-inflammatory drugs and risk of colorectal cancer. JAMA 294:914–23
    [Google Scholar]
  14. 14. 
    Giovannucci E, Egan KM, Hunter DJ et al. 1995. Aspirin and the risk of colorectal cancer in women. N. Engl. J. Med. 333:609–14
    [Google Scholar]
  15. 15. 
    Cook NR, Lee IM, Gaziano JM et al. 2005. Low-dose aspirin in the primary prevention of cancer: the Women's Health Study: a randomized controlled trial. JAMA 294:47–55
    [Google Scholar]
  16. 16. 
    Cook NR, Lee IM, Zhang SM et al. 2013. Alternate-day, low-dose aspirin and cancer risk: long-term observational follow-up of a randomized trial. Ann. Intern. Med. 159:77–85
    [Google Scholar]
  17. 17. 
    Rothwell PM, Price JF, Fowkes FGR et al. 2012. Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials. Lancet 379:1602–12
    [Google Scholar]
  18. 18. 
    Rothwell PM, Wilson M, Elwin CE et al. 2010. Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet 376:1741–50
    [Google Scholar]
  19. 19. 
    Petrucci G, Zaccardi F, Giaretta A et al. 2019. Obesity is associated with impaired responsiveness to once-daily low-dose aspirin and in vivo platelet activation. J. Thromb. Haemost. 17:885–95
    [Google Scholar]
  20. 20. 
    Rothwell PM, Cook NR, Gaziano JM et al. 2018. Effects of aspirin on risks of vascular events and cancer according to bodyweight and dose: analysis of individual patient data from randomised trials. Lancet 392:387–99
    [Google Scholar]
  21. 21. 
    Drew DA, Goh G, Mo A et al. 2016. Colorectal polyp prevention by daily aspirin use is abrogated among active smokers. Cancer Causes Control 27:93–103
    [Google Scholar]
  22. 22. 
    Ishikawa H, Mutoh M, Suzuki S et al. 2014. The preventive effects of low-dose enteric-coated aspirin tablets on the development of colorectal tumours in Asian patients: a randomised trial. Gut 63:1755–59
    [Google Scholar]
  23. 23. 
    Flossmann E, Rothwell PM. 2007. Effect of aspirin on long-term risk of colorectal cancer: consistent evidence from randomised and observational studies. Lancet 369:1603–13
    [Google Scholar]
  24. 24. 
    Burn J, Bishop DT, Mecklin JP et al. 2008. Effect of aspirin or resistant starch on colorectal neoplasia in the Lynch syndrome. N. Engl. J. Med. 359:2567–78
    [Google Scholar]
  25. 25. 
    Burn J, Gerdes AM, Macrae F et al. 2011. Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. Lancet 378:2081–87
    [Google Scholar]
  26. 26. 
    Sandler RS, Halabi S, Baron JA et al. 2003. A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. N. Engl. J. Med. 348:883–90
    [Google Scholar]
  27. 27. 
    Logan RF, Grainge MJ, Shepherd VC et al. 2008. Aspirin and folic acid for the prevention of recurrent colorectal adenomas. Gastroenterology 134:29–38
    [Google Scholar]
  28. 28. 
    Baron JA, Cole BF, Sandler RS et al. 2003. A randomized trial of aspirin to prevent colorectal adenomas. N. Engl. J. Med. 348:891–99
    [Google Scholar]
  29. 29. 
    Hull MA, Sprange K, Hepburn T et al. 2018. Eicosapentaenoic acid and aspirin, alone and in combination, for the prevention of colorectal adenomas (seAFOod Polyp Prevention Trial): a multicentre, randomised, double-blind, placebo-controlled, 2 x 2 factorial trial. Lancet 392:2583–94
    [Google Scholar]
  30. 30. 
    DeCensi A, Gescher A. 2019. An abstract provides “seAFOod” for thought. Cancer Prev. Res. 12:123–24
    [Google Scholar]
  31. 31. 
    Burn J, Sheth H, Elliott F et al. 2020. Cancer prevention with aspirin in hereditary colorectal cancer (Lynch syndrome), 10-year follow-up and registry-based 20-year data in the CAPP2 study: a double-blind, randomised, placebo-controlled trial. Lancet 395:1855–63
    [Google Scholar]
  32. 32. 
    NICE (Natl. Inst. Health Care Excellence) 2020. Colorectal cancer NICE Guideline, Jan. 29. https://www.nice.org.uk/guidance/ng151/resources/colorectal-cancer-pdf-66141835244485
    [Google Scholar]
  33. 33. 
    McNeil JJ, Gibbs P, Orchard SG et al. 2020. Effect of aspirin on cancer incidence and mortality in older adults. J. Natl. Cancer Inst. In press. https://doi.org/10.1093/jnci/djaa114
    [Crossref] [Google Scholar]
  34. 34. 
    Perez RF, Tejedor JR, Bayon GF et al. 2018. Distinct chromatin signatures of DNA hypomethylation in aging and cancer. Aging Cell 17:e12744
    [Google Scholar]
  35. 35. 
    Christensen BC, Houseman EA, Marsit CJ et al. 2009. Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context. PLOS Genet 5:e1000602
    [Google Scholar]
  36. 36. 
    Hannum G, Guinney J, Zhao L et al. 2013. Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol. Cell 49:359–67
    [Google Scholar]
  37. 37. 
    Nawa T, Kato J, Kawamoto H et al. 2008. Differences between right- and left-sided colon cancer in patient characteristics, cancer morphology and histology. J. Gastroenterol. Hepatol. 23:418–23
    [Google Scholar]
  38. 38. 
    Jess P, Hansen IO, Gamborg M et al. 2013. A nationwide Danish cohort study challenging the categorisation into right-sided and left-sided colon cancer. BMJ Open 3:e002608
    [Google Scholar]
  39. 39. 
    Gonsalves WI, Mahoney MR, Sargent DJ et al. 2014. Patient and tumor characteristics and BRAF and KRAS mutations in colon cancer, NCCTG/Alliance N0147. J. Natl. Cancer Inst. 106:dju106
    [Google Scholar]
  40. 40. 
    Ang PW, Loh M, Liem N et al. 2010. Comprehensive profiling of DNA methylation in colorectal cancer reveals subgroups with distinct clinicopathological and molecular features. BMC Cancer 10:227
    [Google Scholar]
  41. 41. 
    Serebriiskii IG, Connelly C, Frampton G et al. 2019. Comprehensive characterization of RAS mutations in colon and rectal cancers in old and young patients. Nat. Commun. 10:3722
    [Google Scholar]
  42. 42. 
    Amitay EL, Carr PR, Jansen L et al. 2019. Association of aspirin and nonsteroidal anti-inflammatory drugs with colorectal cancer risk by molecular subtypes. J. Natl. Cancer Inst. 111:475–83
    [Google Scholar]
  43. 43. 
    Nishihara R, Lochhead P, Kuchiba A et al. 2013. Aspirin use and risk of colorectal cancer according to BRAF mutation status. JAMA 309:2563–71
    [Google Scholar]
  44. 44. 
    Low EE, Demb J, Liu L et al. 2020. Risk factors for early-onset colorectal cancer. Gastroenterology 159:492–501
    [Google Scholar]
  45. 45. 
    Wolf AMD, Fontham ETH, Church TR et al. 2018. Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society. CA Cancer J. Clin. 68:250–81
    [Google Scholar]
  46. 46. 
    Sansom OJ, Stark LA, Dunlop MG, Clarke AR 2001. Suppression of intestinal and mammary neoplasia by lifetime administration of aspirin in ApcMin/+ and ApcMin/+, Msh2–/– mice. Cancer Res 61:7060–64
    [Google Scholar]
  47. 47. 
    Lanas A, Wu P, Medin J, Mills EJ 2011. Low doses of acetylsalicylic acid increase risk of gastrointestinal bleeding in a meta-analysis. Clin. Gastroenterol. Hepatol. 9:762–68.e6
    [Google Scholar]
  48. 48. 
    Mahady SE, Margolis KL, Chan A et al. 2020. Major GI bleeding in older persons using aspirin: incidence and risk factors in the ASPREE randomised controlled trial. Gut In press
    [Google Scholar]
  49. 49. 
    Serebruany VL, Steinhubl SR, Berger PB et al. 2005. Analysis of risk of bleeding complications after different doses of aspirin in 192,036 patients enrolled in 31 randomized controlled trials. Am. J. Cardiol. 95:1218–22
    [Google Scholar]
  50. 50. 
    Rothwell PM, Wilson M, Price JF et al. 2012. Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials. Lancet 379:1591–601
    [Google Scholar]
  51. 51. 
    Whitlock EP, Williams SB, Burda BUet al 2015. Aspirin Use in Adults: Cancer, All-Cause Mortality, and Harms: A Systematic Evidence Review for the U.S. Preventive Services Task Force. Evidence Synthesis No. 132, Rep. No. 13–05193-EF-1 Rockville, MD: Agency Healthc. Res. Quality
    [Google Scholar]
  52. 52. 
    Jacobs EJ, Thun MJ, Bain EB et al. 2007. A large cohort study of long-term daily use of adult-strength aspirin and cancer incidence. J. Natl. Cancer Inst. 99:608–15
    [Google Scholar]
  53. 53. 
    Cao Y, Nishihara R, Wu K et al. 2016. Population-wide impact of long-term use of aspirin and the risk for cancer. JAMA Oncol 2:762–69
    [Google Scholar]
  54. 54. 
    Simon TG, Ma Y, Ludvigsson JF et al. 2018. Association between aspirin use and risk of hepatocellular carcinoma. JAMA Oncol 4:1683–90
    [Google Scholar]
  55. 55. 
    Rothwell PM, Price JF, Fowkes FG et al. 2012. Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials. Lancet 379:1602–12
    [Google Scholar]
  56. 56. 
    Rothwell PM, Fowkes FG, Belch JF et al. 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
    [Google Scholar]
  57. 57. 
    Loomans-Kropp HA, Pinsky P, Cao Y, Chan AT, Umar A 2019. Association of aspirin use with mortality risk among older adult participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. JAMA Netw. . Open 2:e1916729
    [Google Scholar]
  58. 58. 
    Simon TG, Duberg AS, Aleman S et al. 2020. Association of aspirin with hepatocellular carcinoma and liver-related mortality. N. Engl. J. Med. 382:1018–28
    [Google Scholar]
  59. 59. 
    Drew DA, Cao Y, Chan AT 2016. Aspirin and colorectal cancer: the promise of precision chemoprevention. Nat. Rev. Cancer 16:173–86
    [Google Scholar]
  60. 60. 
    Chan AT, Ogino S, Fuchs CS 2007. Aspirin and the risk of colorectal cancer in relation to the expression of COX-2. N. Engl. J. Med. 356:2131–42
    [Google Scholar]
  61. 61. 
    Fink SP, Yamauchi M, Nishihara R et al. 2014. Aspirin and the risk of colorectal cancer in relation to the expression of 15-hydroxyprostaglandin dehydrogenase (HPGD). Sci. Transl. Med. 6:233re2
    [Google Scholar]
  62. 62. 
    Bezawada N, Song M, Wu K et al. 2014. Urinary PGE-M levels are associated with risk of colorectal adenomas and chemopreventive response to anti-inflammatory drugs. Cancer Prev. Res. 7:758–65
    [Google Scholar]
  63. 63. 
    Fedirko V, Bradshaw PT, Figueiredo JC et al. 2015. Urinary metabolites of prostanoids and risk of recurrent colorectal adenomas in the Aspirin/Folate Polyp Prevention Study (AFPPS). Cancer Prev. Res. 8:1061–68
    [Google Scholar]
  64. 64. 
    Franceschi C, Campisi J. 2014. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J. Gerontol. A Biol. Sci. Med. Sci. 69:Suppl. 1S4–S9
    [Google Scholar]
  65. 65. 
    Franceschi C, Zaikin A, Gordleeva S et al. 2018. Inflammaging 2018: an update and a model. Semin. Immunol. 40:1–5
    [Google Scholar]
  66. 66. 
    Wang D, DuBois RN. 2018. Role of prostanoids in gastrointestinal cancer. J. Clin. Investig. 128:2732–42
    [Google Scholar]
  67. 67. 
    Nusse YM, Savage AK, Marangoni P et al. 2018. Parasitic helminths induce fetal-like reversion in the intestinal stem cell niche. Nature 559:109–13
    [Google Scholar]
  68. 68. 
    Yui S, Azzolin L, Maimets M et al. 2018. YAP/TAZ-dependent reprogramming of colonic epithelium links ECM remodeling to tissue regeneration. Cell Stem. Cell 22:35–49.e7
    [Google Scholar]
  69. 69. 
    Roulis M, Kaklamanos A, Schernthanner M et al. 2020. Paracrine orchestration of intestinal tumorigenesis by a mesenchymal niche. Nature 580:524–29
    [Google Scholar]
  70. 70. 
    Wang Y, Chiang IL, Ohara TE et al. 2019. Long-term culture captures injury-repair cycles of colonic stem cells. Cell 179:1144–59.e15
    [Google Scholar]
  71. 71. 
    Qiu W, Wang X, Leibowitz B et al. 2010. Chemoprevention by nonsteroidal anti-inflammatory drugs eliminates oncogenic intestinal stem cells via SMAC-dependent apoptosis. PNAS 107:20027–32
    [Google Scholar]
  72. 72. 
    Moon CM, Kwon JH, Kim JS et al. 2014. Nonsteroidal anti-inflammatory drugs suppress cancer stem cells via inhibiting PTGS2 (cyclooxygenase 2) and NOTCH/HES1 and activating PPARG in colorectal cancer. Int. J. Cancer 134:519–29
    [Google Scholar]
  73. 73. 
    Mihaylova MM, Cheng CW, Cao AQ et al. 2018. Fasting activates fatty acid oxidation to enhance intestinal stem cell function during homeostasis and aging. Cell Stem. Cell 22:769–78.e4
    [Google Scholar]
  74. 74. 
    Pentinmikko N, Iqbal S, Mana M et al. 2019. Notum produced by Paneth cells attenuates regeneration of aged intestinal epithelium. Nature 571:398–402
    [Google Scholar]
  75. 75. 
    Balducci L, Ershler WB. 2005. Cancer and ageing: a nexus at several levels. Nat. Rev. Cancer 5:655–62
    [Google Scholar]
  76. 76. 
    Blokzijl F, de Ligt J, Jager M et al. 2016. Tissue-specific mutation accumulation in human adult stem cells during life. Nature 538:260–64
    [Google Scholar]
  77. 77. 
    Tomasetti C, Vogelstein B. 2015. Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science 347:78–81
    [Google Scholar]
  78. 78. 
    Tomasetti C, Li L, Vogelstein B 2017. Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention. Science 355:1330–34
    [Google Scholar]
  79. 79. 
    Ershler WB, Stewart JA, Hacker MP et al. 1984. B16 murine melanoma and aging: slower growth and longer survival in old mice. J. Natl. Cancer Inst. 72:161–64
    [Google Scholar]
  80. 80. 
    Signer RA, Montecino-Rodriguez E, Witte ON et al. 2007. Age-related defects in B lymphopoiesis underlie the myeloid dominance of adult leukemia. Blood 110:1831–39
    [Google Scholar]
  81. 81. 
    Ishikawa TO, Herschman HR. 2006. Conditional knockout mouse for tissue-specific disruption of the cyclooxygenase-2 (Cox-2) gene. Genesis 44:143–49
    [Google Scholar]
  82. 82. 
    Manieri NA, Mack MR, Himmelrich MD et al. 2015. Mucosally transplanted mesenchymal stem cells stimulate intestinal healing by promoting angiogenesis. J. Clin. Invest. 125:3606–18
    [Google Scholar]
  83. 83. 
    Jain U, Lai CW, Xiong S et al. 2018. Temporal regulation of the bacterial metabolite deoxycholate during colonic repair is critical for crypt regeneration. Cell Host Microbe 24:353–63.e5
    [Google Scholar]
  84. 84. 
    Miyoshi H, VanDussen KL, Malvin NP et al. 2017. Prostaglandin E2 promotes intestinal repair through an adaptive cellular response of the epithelium. EMBO J 36:5–24
    [Google Scholar]
  85. 85. 
    Montrose DC, Nakanishi M, Murphy RC et al. 2015. The role of PGE2 in intestinal inflammation and tumorigenesis. Prostaglandins Other Lipid Mediat 116–117:26–36
    [Google Scholar]
  86. 86. 
    Silla IO, Rueda D, Rodriguez Y et al. 2014. Early-onset colorectal cancer: a separate subset of colorectal cancer. World J. Gastroenterol. 20:17288–96
    [Google Scholar]
  87. 87. 
    Ruschoff J, Wallinger S, Dietmaier W et al. 1998. Aspirin suppresses the mutator phenotype associated with hereditary nonpolyposis colorectal cancer by genetic selection. PNAS 95:11301–6
    [Google Scholar]
  88. 88. 
    Perea J, Rueda D, Canal A et al. 2014. Age at onset should be a major criterion for subclassification of colorectal cancer. J. Mol. Diagn. 16:116–26
    [Google Scholar]
  89. 89. 
    Giraldez MD, Lopez-Doriga A, Bujanda L et al. 2012. Susceptibility genetic variants associated with early-onset colorectal cancer. Carcinogenesis 33:613–19
    [Google Scholar]
  90. 90. 
    Goel A, Nagasaka T, Spiegel J et al. 2010. Low frequency of Lynch syndrome among young patients with non-familial colorectal cancer. Clin. Gastroenterol. Hepatol. 8:966–71
    [Google Scholar]
  91. 91. 
    Loomans-Kropp HA, Umar A. 2019. Cancer prevention and screening: the next step in the era of precision medicine. NPJ Precis. Oncol. 3:3
    [Google Scholar]
  92. 92. 
    Chan AT, Giovannucci EL. 2010. Primary prevention of colorectal cancer. Gastroenterology 138:2029–43.e10
    [Google Scholar]
  93. 93. 
    Song M, Garrett WS, Chan AT 2015. Nutrients, foods, and colorectal cancer prevention. Gastroenterology 148:1244–60.e16
    [Google Scholar]
  94. 94. 
    Collins F. 2015. Precision medicine: who benefits from aspirin to prevent colorectal cancer. NIH Director's Blog Mar. 24. https://directorsblog.nih.gov/2015/03/24/precision-medicine-who-benefits-from-aspirin-to-prevent-colorectal-cancer/
    [Google Scholar]
  95. 95. 
    Mehta RS, Song M, Bezawada N et al. 2014. A prospective study of macrophage inhibitory cytokine-1 (MIC-1/GDF15) and risk of colorectal cancer. J. Natl. Cancer Inst. 106:dju016
    [Google Scholar]
  96. 96. 
    Cai Q, Gao YT, Chow WH et al. 2006. Prospective study of urinary prostaglandin E2 metabolite and colorectal cancer risk. J. Clin. Oncol. 24:5010–16
    [Google Scholar]
  97. 97. 
    Johnson JC, Schmidt CR, Shrubsole MJ et al. 2006. Urine PGE-M: a metabolite of prostaglandin E2 as a potential biomarker of advanced colorectal neoplasia. Clin. Gastroenterol. Hepatol. 4:1358–65
    [Google Scholar]
  98. 98. 
    Cui Y, Shu XO, Li HL et al. 2017. Prospective study of urinary prostaglandin E2 metabolite and pancreatic cancer risk. Int. J. Cancer 141:2423–29
    [Google Scholar]
  99. 99. 
    Zhao J, Wang J, Du J et al. 2015. Urinary prostaglandin E2 metabolite and pancreatic cancer risk: case-control study in urban Shanghai. PLOS ONE 10:e0118004
    [Google Scholar]
  100. 100. 
    Dong LM, Shu XO, Gao YT et al. 2009. Urinary prostaglandin E2 metabolite and gastric cancer risk in the Shanghai women's health study. Cancer Epidemiol. Biomarkers. Prev. 18:3075–78
    [Google Scholar]
  101. 101. 
    Wang T, Cai H, Zheng W et al. 2017. A prospective study of urinary prostaglandin E2 metabolite, Helicobacter pylori antibodies, and gastric cancer risk. Clin. Infect. Dis. 64:1380–86
    [Google Scholar]
  102. 102. 
    Murphey LJ, Williams MK, Sanchez SC et al. 2004. Quantification of the major urinary metabolite of PGE2 by a liquid chromatographic/mass spectrometric assay: determination of cyclooxygenase-specific PGE2 synthesis in healthy humans and those with lung cancer. Anal. Biochem. 334:266–75
    [Google Scholar]
  103. 103. 
    Cui Y, Shu XO, Gao YT et al. 2014. Urinary prostaglandin E2 metabolite and breast cancer risk. Cancer Epidemiol. Biomarkers. Prev. 23:2866–73
    [Google Scholar]
  104. 104. 
    Kim S, Taylor JA, Milne GL, Sandler DP 2013. Association between urinary prostaglandin E2 metabolite and breast cancer risk: a prospective, case-cohort study of postmenopausal women. Cancer Prev. Res. 6:511–18
    [Google Scholar]
  105. 105. 
    Drew DA, Chin SM, Gilpin KK et al. 2017. ASPirin Intervention for the REDuction of colorectal cancer risk (ASPIRED): a study protocol for a randomized controlled trial. Trials 18:50
    [Google Scholar]
  106. 106. 
    Drew DA, Schuck MM, Magicheva-Gupta MV et al. 2020. Effect of low-dose and standard-dose aspirin on PGE2 biosynthesis among individuals with colorectal adenomas: a randomized clinical trial. Cancer Prev. Res. 13:877–88
    [Google Scholar]
  107. 107. 
    Reyes-Uribe L, Wu W, Gelincik O et al. 2020. Naproxen chemoprevention promotes immune activation in Lynch syndrome colorectal mucosa. Gut In press
    [Google Scholar]
  108. 108. 
    Ricciotti E, FitzGerald GA. 2011. Prostaglandins and inflammation. Arterioscler Thromb. Vasc. Biol. 31:986–1000
    [Google Scholar]
  109. 109. 
    Kalinski P. 2012. Regulation of immune responses by prostaglandin E2. J. Immunol. 188:21–28
    [Google Scholar]
  110. 110. 
    Roberts HR, Smartt HJ, Greenhough A et al. 2011. Colon tumour cells increase PGE2 by regulating COX-2 and 15-PGDH to promote survival during the microenvironmental stress of glucose deprivation. Carcinogenesis 32:1741–47
    [Google Scholar]
  111. 111. 
    Wang D, Fu L, Sun H et al. 2015. Prostaglandin E2 promotes colorectal cancer stem cell expansion and metastasis in mice. Gastroenterology 149:1884–95.e4
    [Google Scholar]
  112. 112. 
    Bellamkonda K, Chandrashekar NK, Osman J et al. 2016. The eicosanoids leukotriene D4 and prostaglandin E2 promote the tumorigenicity of colon cancer-initiating cells in a xenograft mouse model. BMC Cancer 16:425
    [Google Scholar]
  113. 113. 
    Jia W, Xie G, Jia W 2018. Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis. Nat. Rev. Gastroenterol. Hepatol. 15:111–28
    [Google Scholar]
  114. 114. 
    Fu T, Coulter S, Yoshihara E et al. 2019. FXR regulates intestinal cancer stem cell proliferation. Cell 176:1098–112.e18
    [Google Scholar]
  115. 115. 
    Kaiko GE, Ryu SH, Koues OI et al. 2016. The colonic crypt protects stem cells from microbiota-derived metabolites. Cell 165:1708–20
    [Google Scholar]
  116. 116. 
    Ahn J, Sinha R, Pei Z et al. 2013. Human gut microbiome and risk for colorectal cancer. J. Natl. Cancer Inst. 105:1907–11
    [Google Scholar]
  117. 117. 
    Brennan CA, Garrett WS. 2016. Gut microbiota, inflammation, and colorectal cancer. Annu. Rev. Microbiol. 70:395–411
    [Google Scholar]
  118. 118. 
    Maier L, Pruteanu M, Kuhn M et al. 2018. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature 555:623–28
    [Google Scholar]
  119. 119. 
    Rogers MAM, Aronoff DM. 2016. The influence of non-steroidal anti-inflammatory drugs on the gut microbiome. Clin. Microbiol. Infect. 22:178.e1–e9
    [Google Scholar]
  120. 120. 
    Imhann F, Bonder MJ, Vich Vila A et al. 2016. Proton pump inhibitors affect the gut microbiome. Gut 65:740–48
    [Google Scholar]
  121. 121. 
    Jackson MA, Goodrich JK, Maxan ME et al. 2016. Proton pump inhibitors alter the composition of the gut microbiota. Gut 65:749–56
    [Google Scholar]
  122. 122. 
    Forslund K, Hildebrand F, Nielsen T et al. 2015. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature 528:262–66
    [Google Scholar]
  123. 123. 
    Flowers SA, Evans SJ, Ward KM et al. 2017. Interaction between atypical antipsychotics and the gut microbiome in a bipolar disease cohort. Pharmacotherapy 37:261–67
    [Google Scholar]
  124. 124. 
    Biarc J, Nguyen IS, Pini A et al. 2004. Carcinogenic properties of proteins with pro-inflammatory activity from Streptococcus infantarius (formerly S. bovis). Carcinogenesis 25:1477–84
    [Google Scholar]
  125. 125. 
    Ellmerich S, Scholler M, Duranton B et al. 2000. Promotion of intestinal carcinogenesis by Streptococcus bovis. . Carcinogenesis 21:753–56
    [Google Scholar]
  126. 126. 
    Wang X, Huycke MM. 2007. Extracellular superoxide production by Enterococcus faecalis promotes chromosomal instability in mammalian cells. Gastroenterology 132:551–61
    [Google Scholar]
  127. 127. 
    Kostic AD, Gevers D, Pedamallu CS et al. 2012. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res 22:292–98
    [Google Scholar]
  128. 128. 
    Zhu Q, Gao R, Wu W, Qin H 2013. The role of gut microbiota in the pathogenesis of colorectal cancer. Tumour Biol 34:1285–300
    [Google Scholar]
  129. 129. 
    Zhao R, Coker OO, Wu J et al. 2020. Aspirin reduces colorectal tumor development in mice and gut microbes reduce its bioavailability and chemopreventive effects. Gastroenterology 159:3969–83
    [Google Scholar]
  130. 130. 
    Prizment AE, Staley C, Onyeaghala GC et al. 2020. Randomised clinical study: oral aspirin 325 mg daily vs placebo alters gut microbial composition and bacterial taxa associated with colorectal cancer risk. Aliment. Pharmacol. Ther. In press
    [Google Scholar]
  131. 131. 
    Drew DA, Chan AT. 2018. Towards a cancer-chemopreventive diet. Nat. Biomed. Eng. 2:6–7
    [Google Scholar]
  132. 132. 
    Ho CL, Tan HQ, Chua KJ et al. 2018. Engineered commensal microbes for diet-mediated colorectal-cancer chemoprevention. Nat. Biomed. Eng. 2:27–37
    [Google Scholar]
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