Aspirin and Colorectal Cancer Prevention and Treatment: Is It for Everyone?

Current Colorectal Cancer Reports

Volumn 12, Issue 1, 2016, Pages 27-34

  Coyle, Christopher ^a   Cafferty, Fay Helen ^a   Langley, Ruth Elizabeth ^a  

^a MRC CLINICAL TRIALS UNIT   (United Kingdom)

Author keywords

Acetylsalicylic acid; Adjuvant therapy; Aspirin; Bleeding; BRAF; Chemoprevention; Colorectal cancer; Human leukocyte antigen; NSAID; PIK3CA; Primary prevention; Secondary prevention; Single nucleotide polymorphism

Indexed keywords

ACETYLSALICYLIC ACID; CYCLOOXYGENASE 2; HLA ANTIGEN CLASS 1; TUMOR MARKER;

BLEEDING; BLEEDING TENDENCY; BLOOD CLOTTING DISORDER; BRAIN HEMORRHAGE; CANCER CHEMOTHERAPY; CANCER DIAGNOSIS; CANCER GENETICS; CANCER PREVENTION; CANCER RISK; COLORECTAL ADENOMA; COLORECTAL CANCER; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; DYSPEPSIA; FAMILIAL COLON POLYPOSIS; GASTROINTESTINAL HEMORRHAGE; GENE; GENE MUTATION; HUMAN; MOLECULAR GENETICS; NONHUMAN; PEPTIC ULCER; PERSONALIZED MEDICINE; PIK3CA GENE; PROTEIN EXPRESSION; REVIEW; RISK BENEFIT ANALYSIS; SINGLE NUCLEOTIDE POLYMORPHISM; TREATMENT RESPONSE;

EID: 84957674785     PISSN: 15563790     EISSN: 15563804     Source Type: Journal    
DOI: 10.1007/s11888-016-0306-9     Document Type: Review

References (54)

1. Cole BF, Logan RF, Halabi S, Benamouzig R, Sandler RS, Grainge MJ, et al. Aspirin for the chemoprevention of colorectal adenomas: meta-analysis of the randomized trials. JNCI J Natl Cancer Inst. 2009;101(4):256–66.
2. Cook NR, Lee IM, Zhang SM, Moorthy MV, Buring JE. Alternate-day, low-dose aspirin and cancer risk: long-term observational follow-up of a randomized trial. Ann Intern Med. 2013;159(2):77–85. This study reports long-term follow-up data from the Women’s Health Study. Importantly, it shows that long-term follow-up is necessary to detect the anti-cancer effects of aspirin.
3. Rothwell PM, Wilson M, Elwin CE, Norrving B, Algra A, Warlow CP, et al. Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet. 2010;376(9754):1741–50.
4. Langley RE, Burdett S, Tierney JF, Cafferty F, Parmar MK, Venning G. Aspirin and cancer: has aspirin been overlooked as an adjuvant therapy? Br J Cancer. 2011;105(8):1107–13.
5. Langley RE. Clinical evidence for the use of aspirin in the treatment of cancer. Ecancermedicalscience. 2013;(7). This review gives an update on the evidence supporting aspirin use in the adjuvant setting.
6. Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, Peto R, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373(9678):1849–60.
7. Thorat MA, Cuzick J. Prophylactic use of aspirin: systematic review of harms and approaches to mitigation in the general population. Eur J Epidemiol. 2015;30(1):5–18. This is the most recent systematic review of the harms of aspirin use in the general population, and describes potential strategies to mitigate the risks of adverse effects.
8. Craven PA, DeRubertis FR. Effects of aspirin on 1,2-dimethylhydrazine-induced colonic carcinogenesis. Carcinogenesis. 1992;13(4):541–6.
9. Reddy BS, Rao CV, Rivenson A, Kelloff G. Inhibitory effect of aspirin on azoxymethane-induced colon carcinogenesis in F344 rats. Carcinogenesis. 1993;14(8):1493–7.
10. Barnes CJ, Lee M. Chemoprevention of spontaneous intestinal adenomas in the adenomatous polyposis coli Min mouse model with aspirin. Gastroenterology. 1998;114(5):873–7.
11. Kune GA, Kune S, Watson LF. Colorectal cancer risk, chronic illnesses, operations, and medications: case control results from the Melbourne Colorectal Cancer Study. Cancer Res. 1988;48(15):4399–404.
12. Bosetti C, Rosato V, Gallus S, Cuzick J, La Vecchia C. Aspirin and cancer risk: a quantitative review to 2011. Ann Oncol. 2012;23(6):1403–15.
13. Ruder EH, Laiyemo AO, Graubard BI, Hollenbeck AR, Schatzkin A, Cross AJ. Non-steroidal anti-inflammatory drugs and colorectal cancer risk in a large, prospective cohort. Am J Gastroenterol. 2011;106(7):1340–50.
14. Friis S, Riis AH, Erichsen R, Baron JA, Sorensen HT. Low-Dose Aspirin or Nonsteroidal Anti-inflammatory Drug Use and Colorectal Cancer Risk: A Population-Based, Case-Control Study. Ann Intern Med. 2015. This is the most recent study supporting the role of aspirin in the prevention of colorectal cancer.
15. Burn J, Gerdes AM, Macrae F, Mecklin JP, Moeslein G, Olschwang S, et al. Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. Lancet. 2012;378(9809):2081–7.
16. Movahedi M, Bishop DT, Macrae F, Mecklin JP, Moeslein G, Olschwang S, et al. Obesity, Aspirin, and Risk of Colorectal Cancer in Carriers of Hereditary Colorectal Cancer: A Prospective Investigation in the CAPP2 Study. J Clin Oncol. 2015. This sub-analysis of the CAPP2 trial shows that obesity may identify those who stand to benefit most from aspirin use in those with Lynch syndrome.
17. Burn J, Bishop DT, Chapman PD, Elliott F, Bertario L, Dunlop MG, et al. A randomized placebo-controlled prevention trial of aspirin and/or resistant starch in young people with familial adenomatous polyposis. Cancer Prev Res (Phila). 2011;4(5):655–65.
18. Kelloff GJ, Schilsky RL, Alberts DS, Day RW, Guyton KZ, Pearce HL, et al. Colorectal adenomas: a prototype for the use of surrogate end points in the development of cancer prevention drugs. Clin Cancer Res. 2004;10(11):3908–18.
19. Nan H, Morikawa T, Suuriniemi M, Imamura Y, Werner L, Kuchiba A, et al. Aspirin Use, 8q24 Single Nucleotide Polymorphism rs6983267, and Colorectal Cancer According to CTNNB1 Alterations. J Natl Cancer Inst. 2013. This recent study reported that a particular SNP may identify those who benefit from aspirin use for the chemoprevention of colorectal cancer.
20. Nan H, Hutter CM, Lin Y, Jacobs EJ, Ulrich CM, White E, et al. Association of aspirin and NSAID use with risk of colorectal cancer according to genetic variants. JAMA. 2015;313(11):1133–42. This recent study reports that two further single-nucleotide polymorphisms may identify those who benefit from aspirin use for the chemoprevention of colorectal cancer.
21. Tang X, Sun YJ, Half E, Kuo MT, Sinicrope F. Cyclooxygenase-2 overexpression inhibits death receptor 5 expression and confers resistance to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in human colon cancer cells. Cancer Res. 2002;62(17):4903–8.
22. Elder DJ, Hague A, Hicks DJ, Paraskeva C. Differential growth inhibition by the aspirin metabolite salicylate in human colorectal tumor cell lines: enhanced apoptosis in carcinoma and in vitro-transformed adenoma relative to adenoma relative to adenoma cell lines. Cancer Res. 1996;56(10):2273–6.
23. Cardwell CR, Kunzmann AT, Cantwell MM, Hughes C, Baron JA, Powe DG, et al. Low-dose Aspirin Use After Diagnosis of Colorectal Cancer Does not Increase Survival: a Case-Control Analysis of a Population-Based Cohort. Gastroenterology. 2013. This case-control study utilising UK General Practice data does not show the trend seen in other studies towards an improvement in colorectal cancer outcomes with aspirin use.
24. Chan AT, Ogino S, Fuchs CS. Aspirin use and survival after diagnosis of colorectal cancer. JAMA. 2009;302(6):649–58.
25. Bains S, Mahic M, Cvancarova M, Yaqub S, Dørum ML, Bjørnbeth BA, et al. Impact of aspirin as secondary prevention in an unselected cohort of 25,644 patients with colorectal cancer: a population-based study. J Clin Oncol 2015;33(suppl; abstr 3504).
26. Bastiaannet E, Sampieri K, Dekkers OM, de Craen AJ, van Herk-Sukel MP, Lemmens V, et al. Use of aspirin postdiagnosis improves survival for colon cancer patients. Br J Cancer. 2012;106(9):1564–70.
27. McCowan C, Munro AJ, Donnan PT, Steele RJ. Use of aspirin post-diagnosis in a cohort of patients with colorectal cancer and its association with all-cause and colorectal cancer specific mortality. Eur J Cancer. 2013;49(5):1049–57.
28. Ng K, Meyerhardt JA, Chan AT, Sato K, Chan JA, Niedzwiecki D, et al. Aspirin and COX-2 inhibitor use in patients with stage III colon cancer. J Natl Cancer Inst. 2015;107(1):345. This is the most recent study to suggest that aspirin has a role in the adjuvant treatment of cancer.
29. Walker AJ, Grainge MJ, Card TR. Aspirin and other non-steroidal anti-inflammatory drug use and colorectal cancer survival: a cohort study. Br J Cancer. 2012;107(9):1602–7.
30. Rothwell PM, Wilson M, Price JF, Belch JF, Meade TW, Mehta Z. Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials. Lancet. 2012;379(9826):1591–601.
31. Tiano HF, Loftin CD, Akunda J, Lee CA, Spalding J, Sessoms A, et al. Deficiency of either cyclooxygenase (COX)-1 or COX-2 alters epidermal differentiation and reduces mouse skin tumorigenesis. Cancer Res. 2002;62(12):3395–401.
32. Thun MJ, Jacobs EJ, Patrono C. The role of aspirin in cancer prevention. Nat Rev Clin Oncol. 2012;9(5):259–67.
33. Reimers MS, Bastiaannet E, Langley RE, van Eijk R, van Vlierberghe RL, Lemmens VE, et al. Expression of HLA Class-I Antigen, Aspirin Use, and Survival After a Diagnosis of Colon Cancer. JAMA Intern Med. 2014. This recent study is the first to investigate the role of HLA class I expression on colorectal cancer outcomes in relation to aspirin use.
34. Holmes MD, Chen WY, Schnitt SJ, Collins L, Colditz GA, Hankinson SE, et al. COX-2 expression predicts worse breast cancer prognosis and does not modify the association with aspirin. Breast Cancer Res Treat. 2011;130(2):657–62.
35. Placke T, Orgel M, Schaller M, Jung G, Rammensee HG, Kopp HG, et al. Platelet-derived MHC class I confers a pseudonormal phenotype to cancer cells that subverts the antitumor reactivity of natural killer immune cells. Cancer Res. 2012;72(2):440–8.
36. Liao X, Lochhead P, Nishihara R, Morikawa T, Kuchiba A, Yamauchi M, et al. Aspirin use, tumor PIK3CA mutation, and colorectal-cancer survival. N Engl J Med. 2012;367(17):1596–606.
37. Domingo E, Church DN, Sieber O, Ramamoorthy R, Yanagisawa Y, Johnstone E, et al. Evaluation of PIK3CA mutation as a predictor of benefit from nonsteroidal anti-inflammatory drug therapy in colorectal cancer. J Clin Oncol. 2013;31(34):4297–305. This study investigated the role of PIK3CA mutation status on colorectal cancer outcomes and was the first to corroborate the effect seen in the study by Liao et.al.
38. Kothari N, Kim R, Jorissen RN, Desai J, Tie J, Wong HL, et al. Impact of regular aspirin use on overall and cancer-specific survival in patients with colorectal cancer harboring a PIK3CA mutation. Acta Oncol. 2015;54(4):487–92. This is the most recent study to investigate the effects of aspirin in PIK3CA mutant colorectal cancer. No significant improvement in overall survival or cancer-specific survival was observed with aspirin use in those with PIK3CA-mutated colorectal cancer.
39. Nishihara R, Lochhead P, Kuchiba A, Jung S, Yamauchi M, Liao X, et al. Aspirin use and risk of colorectal cancer according to BRAF mutation status. JAMA. 2013;309(24):2563–71. This study examined the role of colorectal cancer BRAF mutation status in relation to aspirin use and found that users had a lower risk of developing a BRAF wild-type tumour.
40. Jack DB. One hundred years of aspirin. Lancet. 1997;350(9075):437–9.
41. Electronic Medicines Compendium (eMC) SPC aspirin tablets BP 75 mg. 2014. http://www.medicines.org.uk/emc/medicine/26656/SPC.
42. Cayla G, Collet JP, Silvain J, Thiefin G, Woimant F, Montalescot G. Prevalence and clinical impact of upper gastrointestinal symptoms in subjects treated with low dose aspirin: the UGLA survey. Int J Cardiol. 2012;156(1):69–75.
43. Fletcher EH, Johnston DE, Fisher CR, Koerner RJ, Newton JL, Gray CS. Systematic review: Helicobacter pylori and the risk of upper gastrointestinal bleeding risk in patients taking aspirin. Aliment Pharmacol Ther. 2010;32(7):831–9.
44. Arisawa T, Tahara T, Shibata T, Nagasaka M, Nakamura M, Kamiya Y, et al. Association between genetic polymorphisms in the cyclooxygenase-1 gene promoter and peptic ulcers in Japan. Int J Mol Med. 2007;20(3):373–8.
45. Pilotto A, Seripa D, Franceschi M, Scarcelli C, Colaizzo D, Grandone E, et al. Genetic susceptibility to nonsteroidal anti-inflammatory drug-related gastroduodenal bleeding: role of cytochrome P450 2C9 polymorphisms. Gastroenterology. 2007;133(2):465–71.
46. Martinez C, Blanco G, Ladero JM, Garcia-Martin E, Taxonera C, Gamito FG, et al. Genetic predisposition to acute gastrointestinal bleeding after NSAIDs use. Br J Pharmacol. 2004;141(2):205–8.
47. US Preventative Services Task Force. Aspirin to Prevent Cardiovascular Disease and Cancer. 2016. Available from: http://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryDraft/aspirin-to-prevent-cardiovascular-disease-and-cancer?ds=1&s=aspirin.
48. Floyd CN, Ferro A. Mechanisms of aspirin resistance. Pharmacol Ther. 2014;141(1):69–78.
49. Santilli F, Rocca B, De Cristofaro R, Lattanzio S, Pietrangelo L, Habib A, et al. Platelet cyclooxygenase inhibition by low-dose aspirin is not reflected consistently by platelet function assays. J Am Coll Cardiol. 2009;53(8):667–77.
50. Dawson J, Quinn T, Rafferty M, Higgins P, Ray G, Lees KR, et al. Aspirin resistance and compliance with therapy. Cardiovasc Ther. 2010.
51. Rocca B, Santilli F, Pitocco D, Mucci L, Petrucci G, Vitacolonna E, et al. The recovery of platelet cyclooxygenase activity explains interindividual variability in responsiveness to low-dose aspirin in patients with and without diabetes. J Thromb Haemost. 2012;10(7):1220–30.
52. Cuzick J, Thorat MA, Bosetti C, Brown PH, Burn J, Cook NR, et al. Estimates of benefits and harms of prophylactic use of aspirin in the general population. Ann Oncol. 2014. This article extensively reviews the overall risk-benefit profile of aspirin for the primary prevention of colorectal cancer.
53. Simon R. Advances in clinical trial designs for predictive biomarker discovery and validation. Curr Breast Cancer Rep. 2009;1(4):216–21.
54. Goh CH, Leong WQ, Chew MH, Pan YS, Tony LK, Chew L, et al. Post-operative aspirin use and colorectal cancer-specific survival in patients with stage I-III colorectal cancer. Anticancer Res. 2014;34(12):7407–14. This study assessed the effects of aspirin on colorectal cancer specific survival in a predominantly Asian population and found a trend towards benefit with aspirin use.