[Picture Credit: Felix Hoffman]

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1 Cancer Assciatin f Suth Africa (CANSA) Fact Sheet and Psitin Statement n Aspirin Intrductin Aspirin is part f a grup f medicatins called nn-steridal anti-inflammatry drugs (NSAIDs), but differs frm mst ther NSAIDs in its mechanism f actin. Thugh it, and thers with similar structure, called the salicylates, have similar effects [antipyretic (reductin f fever), antiinflammatry, and analgesic] t the ther NSAIDs and inhibit the same enzyme cyclxygenase (COX), aspirin des s in an irreversible manner and, unlike thers, affects mre the COX-1 variant than the COX-2 variant f the enzyme (Burke, Smythe & FitzGerald, 2006). The active ingredient f Aspirin was first discvered frm the bark f the willw tree in 1763 by the Reverend Edward Stne (Church f England Rectr) f Wadham Cllege, Oxfrd University. He had discvered salicylic acid, the active metablite f aspirin. Aspirin was first synthesised by Felix Hffman, a chemist with the German cmpany Bayer in [Picture Credit: Felix Hffman] Aspirin is ne f the mst widely used medicatins in the wrld, with an estimated tns f it being cnsumed each year. In cuntries where Aspirin is a registered trademark wned by Bayer, the generic term is acetylsalicylic acid (ASA). It is n the Wrld Health Organizatin s List f Essential Medicines, a list f the mst imprtant medicatins needed in a basic health system. (Wrld Health Organizatin; Wikipedia). A Warning Against the Indiscriminate Use f Aspirin Althugh taking an ccasinal aspirin r tw is safe fr mst adults t use fr headaches, bdy aches r fever, daily use f aspirin can have serius side effects, including internal bleeding. One shuld take a daily aspirin nly if ne s dctr advises t d s. If ne has had a heart attack r strke, a dctr will likely recmmend taking a daily aspirin unless there is evidence f a serius allergy r histry f bleeding. If smene has a high risk f having a first heart attack, a dctr might recmmend aspirin after weighing the risks and benefits. N ne shuld start daily aspirin therapy n their wn (May Clinic). Researched and Authred by Prf Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupatinal Health] Apprved by Ms Elize Jubert, Chief Executive Officer [BA Scial Wrk (cum laude); MA Scial Wrk] March 2017 Page 1

2 One shuld nt use aspirin if ne has a bleeding disrder such as haemphilia, a recent histry f stmach r intestinal bleeding, r if ne is allergic t a nn-steridal anti-inflammatry drug (NSAID) such as Advil, Mtrin, Aleve, Orudis, Indcin, Ldine, Vltaren, Tradl, Mbic, Relafen, Feldene, and thers. Even thugh aspirin is freely available, it shuld nt be given indiscriminately t a child r teenager with a fever, flu symptms, r chicken px as it can cause Reye's syndrme (a rare but serius illness that can affect the brain and liver that ccurs mst cmmnly in kids recvering frm a viral infectin), a serius and smetimes fatal cnditin in children. [Picture Credit: Aspirin Side Effects] T make sure aspirin is safe t use, ne shuld infrm ne s dctr abut: asthma r seasnal allergies stmach ulcers liver disease kidney disease a bleeding r bld cltting disrder heart disease, high bld pressure, r cngestive heart failure gut nasal plyps Aspirin may be harmful t an unbrn baby's heart, and may als reduce birth weight r have ther dangerus effects. Wmen shuld infrm their dctr if they are pregnant r plan t becme pregnant while taking aspirin. Aspirin can pass int breast milk and may harm a nursing baby. Wmen shuld, therefre, nt breast-feed while using this medicine. (Drugs.cm). Aspirin and Nn-Cmmunicable Diseases Nn-cmmunicable diseases (NCDs) accunted fr tw f every three deaths (34,5 millin) wrldwide in An imprtant way t tackle cardivascular diseases (CVD) inclusive f strke preventin is t encurage peple t adpt healthier behaviurs and diets as well as the use f life-lng aspirin (daily, lw dse) fr secndary preventin f CVD as this is well established and included in many evidence-based guidelines (Algra, 2013). This shuld, hwever, nly be dne after cnsultatin with a medical practitiner. Aspirin and Reducing the Risk fr Cancer The fllwing are recrded scientific findings n Aspirin and cancer: Researched and Authred by Prf Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupatinal Health] Apprved by Ms Elize Jubert, Chief Executive Officer [BA Scial Wrk (cum laude); MA Scial Wrk] March 2017 Page 2

3 Lwering the Risk fr Cancer Nt everyne shuld start swallwing a daily aspirin. The drug cmes with sme very real drawbacks - mst ntably an increased risk fr internal bleeding. That is especially true amng lder adults r thse wh drink alchl, have a histry f ulcers, r wh take anticagulant drugs. The risk f bleeding may be t great t recmmend an aspirin regimen, research suggests. While bleeding risks are lwer amng peple taking lw-dse aspirin cmpared t thse n full-strength versins f the drug, aspirin swallwers are still twice as likely t suffer frm lifethreatening bleeding cmpared t thse nt n aspirin. Lw dses f aspirin r baby aspirin are generally 81 milligrams. A daily lw-dse aspirin (81mg) may make sense fr peple at high risk fr certain types f cancer, but the ptential side effects mean aspirin certainly is nt fr everyne. Only ne s dctr can help ne weigh the benefits against the risks. Patients receiving cancer treatment culd increase their chance f survival by up t 20% and help stp their cancer frm spreading by taking a lw-dse f aspirin, new research suggests. In a systematic review f the available scientific literature a team frm Cardiff University's Schl f Medicine fund a significant reductin in mrtality and cancer spread by patients wh tk a lw-level dse f aspirin in additin t their cancer treatment (average study fllw-up length ver 5 years). The researchers fund that there is a grwing bdy f evidence that taking aspirin is f significant benefit in reducing sme cancers. Whilst it is knwn that a lw-dse f aspirin has been shwn t reduce the incidence f cancer, its rle in the treatment f cancer remains uncertain. The team's review lked at all f the available data including five randmised trials and frty tw bservatinal studies f clrectal, breast and prstate cancers. (MD Andersn Cancer Center; Science Daily; Elwd, et al, 2016). Aspirin can lwer cancer mrtality There is sme evidence frm randmised trials that shrt-term (2 3 years) aspirin use can lwer cancer mrtality. When cmpared with cntrls, aspirin use resulted in fewer deaths due t cancer. Aspirin als tended t reduce the incidence f female reprductive cancers and death due t clrectal cancer and lymphma (Yelsengekar & Mahandas, 2012). Aspirin and a decreased risk fr cancer Accrding t Pasche, et al. (2014) an assciatin between intake f aspirin and decreased cancer risk was identified in the past decades. Whether aspirin can be used as an anticancer agent in patients with a diagnsis f cancer was unknwn until recently. Recent studies suggest that aspirin might prvide therapeutic benefit in the adjuvant treatment f certain frms f cancer. Aspirin, lifestyle and cln cancer Lifestyle, including aspirin use, has the effect f mdulating age-assciated DNA methylatin changes in the clnic epithelium and thereby impacts the evlutin f cancer methylmes in cln cancer (Nreen, et al., 2014). Researched and Authred by Prf Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupatinal Health] Apprved by Ms Elize Jubert, Chief Executive Officer [BA Scial Wrk (cum laude); MA Scial Wrk] March 2017 Page 3

4 In a study carried ut by researchers frm a number f institutins acrss Eurpe and the US, including Queen Mary University f Lndn, it was fund that peple aged between 50 and 65 wh take aspirin every day fr 10 years culd cut their risk f bwel cancer by 30% and cancers f the thrat and stmach by 25%, accrding t the study published in the Annals f Onclgy. Aspirin is an antiplatelet, which means it reduces the risk f clts frming in yur bld. Platelets may als prtect cancer cells in the bdy, and it has been suggested aspirin's effect n them may hinder this prcess. Hwever, the exact mechanism is nt well understd and mre research is needed. Taking aspirin every day cmes with a serius health warning as it can cause serius side effects such as ulcers and bleeding frm the stmach, particularly in elderly peple. Hwever, the researchers argue the benefits f taking the drug need t be balanced against the harms. Anyne thinking f taking aspirin fr preventin shuld talk t their medical practitiner first (NHS Chices.UK; WebMD). The earliest and strngest evidence that aspirin can prevent cancer emerged frm studies shwing that a daily dse f aspirin reduced the risk f clrectal cancer by 20%. Early n, it appeared that peple had t take aspirin fr at least five years t reduce their risk f develping cancer, but sme f the newer studies suggest that 2 years may als help prevent cancer (Bker). Aspirin as a prmising agent fr cancer preventin and treatment High-quality evidence suggests that aspirin is a prmising agent fr cancer preventin and treatment. Direct inhibitin f cyclxygenase-2 (COX-2) pathway is generally thught t be the main mechanism by which aspirin inhibits cancer develpment. Hwever, either pharmaclgical prperties f aspirin r recent results f epidemilgic studies d nt supprt that mechanism. T address this incnsistency, we hypthesize that antiplatelet effect f aspirin via inhibitin f COX-1 may be ne f ptential mechanisms t inhibit carcingenesis. Aberrant platelet activatin will lead t prmte hstility f tumur micrenvirnment by releasing an abundant array f angigenesis regulatrs. Given the utstanding ability f antiplatelet, aspirin may restre balance f pr- and anti-angigenic factrs released frm platelet t "nrmalise" tumur vasculature and shape tumur micrenvirnment t sme extent, which will nt nly diminish tumur aggressiveness and prgressin, but als enhance the sensitivity t therapeutic treatment. Thus, targeting the platelet activatin leading t alter tumur micrenvirnment may prvide a nvel way t tumur therapy (Su, et al., 2014). Anti-cancer effects f Aspirin Accrding t Alfns, et al., (2104) Salicylates frm plant surces have been used fr centuries by different cultures t treat a variety f ailments such as inflammatin, fever and pain. A chemical derivative f salicylic acid, aspirin, was synthesised and mass prduced by the end f the 19th century and is ne f the mst widely used drugs in the wrld. Its cardiprtective prperties are well established; hwever, recent evidence shws that it can als act as a chem-preventive agent. Its antithrmbtic and anti-inflammatry actins ccur thrugh the inhibitin f cyclxygenases. The precise mechanisms leading t its anticancer effects are nt clearly established, althugh multiple mechanisms affecting enzyme activity, transcriptin factrs, cellular signalling and mitchndrial functins have been prpsed. This review presents a brief accunt f the majr COX-dependent and independent pathways described in cnnectin with aspirin's anticancer effects. Aspirin's unique ability t acetylate bimlecules besides COX has nt been thrughly investigated nr have all the targets f its primary metablite, salicylic acid been identified. Recent reprts n the ability Researched and Authred by Prf Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupatinal Health] Apprved by Ms Elize Jubert, Chief Executive Officer [BA Scial Wrk (cum laude); MA Scial Wrk] March 2017 Page 4

5 f aspirin t acetylate multiple cellular prteins warrant a cmprehensive study t investigate the rle f this psttranslatinal mdificatin in its anticancer effects. In this review, we als raise the intriguing pssibility that aspirin may interact and acetylate cellular mlecules such as RNA, and metablites such as CA, leading t a change in their functin. Aspirin and esphageal cancer Aspirin is the mst widely used amng all nnsteridal anti-inflammatry drugs (NSAIDs), which is cheap and acceptable t patients. Several bservatinal results prvide the further investigatin f preventin and therapy f aspirin r similar drugs in esphageal cancer. Data frm case cntrl studies, chrt studies and randmized cntrlled trials (RCTs) als give sme supprt f a beneficial rle f aspirin n esphageal squamus cell carcinma (ESCC). Experimental data suggest that aspirin may prevent carcingenesis f ESCC by favurably affecting prliferatin, apptsis, r ther as yet unidentified grwth-regulating prcesses. But the mechanism by which aspirin influence n esphageal squamus cell carcinma needs further investigatin (Li, Cheng & Zhang, 2014). Aspirin and varian cancer Taking aspirin daily may cut a wman s risk f varian cancer by 20%, accrding t a study published February 6, 2014 in the Jurnal f the Natinal Cancer Institute. This new research adds t the large number f studies cnducted in recent years shwing aspirin may help prevent certain types f cancers (American Cancer Sciety). Aspirin and Pancreatic Cancer Regular use f aspirin by peple living in Shanghai, China, was assciated with decreased risk fr develping pancreatic cancer, accrding t data published in Cancer Epidemilgy, Bimarkers & Preventin, a jurnal f the American Assciatin fr Cancer Research. Data frm this new study and meta-analysis f data frm 18 ther studies suggest that ver the past tw decades, as the general ppulatin's use f aspirin has increased, the effect f aspirin in decreasing pancreatic cancer risk has becme mre prnunced (Science Daily). The Daily Aspirin Dse Matters A standard dse f aspirin (ne pill) is typically 325 mgs, and a lw-dse r baby aspirin is 81mg. Althugh called baby aspirin, children under 12 shuld nt take aspirin due t the risk f Reye s Syndrme. In a study that cmpared daily use f very lw dse aspirin (30mg) t a daily dse f 283mg fr preventing vascular events, researchers fund n significant difference in cancer deaths between the tw grups. In six studies f daily lw-dse aspirin use (75 t 100 mg) fr preventing vascular events, aspirin reduced the risk fr cancer by almst 25% after at least 3 years f aspirin therapy. Daily aspirin use appeared t be particularly beneficial in reducing the risk fr certain cancers f the female reprductive rgans. Fr instance, there were significantly fewer cases f uterine cancer amng the wmen taking aspirin every day than amng the wmen wh did nt take aspirin (zer cases amng wmen taking aspirin as cmpared t 9 cases in the nn-aspirin grup). [Picture Credit: Aspirin] Researched and Authred by Prf Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupatinal Health] Apprved by Ms Elize Jubert, Chief Executive Officer [BA Scial Wrk (cum laude); MA Scial Wrk] March 2017 Page 5

6 At dses as lw as 75mg, daily aspirin nt nly lwered the risk f heart attack and strke, but it appears t have prevented many types f cancer, including cln cancer and uterine cancer, as well as slwed the spread f cancer t distant rgans. The usual dse that is prescribed is 81mg daily. Higher aspirin dses, which increase the risk f ulcer and internal bleeding, did nt appear t wrk any better. While these studies are exciting and reveal aspirin t be mre f a wnder drug than we ever imagined, it is imprtant t remember that aspirin therapy is NOT fr everyne. Aspirin belngs t a grup f medicatins knwn as bld thinners. These drugs prevent the bdy frm making ptentially harmful clts that can blck bld vessels and cause heart attacks and strkes. Patients already taking bld thinners wh take aspirin may be at an increased risk fr internal bleeding, ranging frm mild t life-threatening. Thse with severe liver and kidney disease are warned against using aspirin given the ptentially txic effects n these rgans. In additin, asthma patients may be particularly sensitive t aspirin and can, as a result, experience asthma-related cmplicatins (Bker). Nt all ver-the-cunter pain relievers cntain aspirin. If a health care prvider prescribes daily aspirin t lwer the risk f a heart attack and clt-related strke, r t assist in lwering the risk fr cancer, read the labels carefully t make sure it is the right prduct. Sme drugs cmbine aspirin with ther pain relievers r ther ingredients and shuld nt be used fr lng-term aspirin therapy (US Fd and Drug Administratin). CANSA s Psitin n Aspirin Even thugh Aspirin (salicylic acid) is cheap and freely available, CANSA believes that: Aspirin is, indeed, a wnder drug, hwever, it shuld be used with cautin Althugh taking an ccasinal aspirin r tw wuld be safe fr mst adults t use t treat headaches, bdy aches r fever, daily use f aspirin can have serius side effects, including internal bleeding and allergic reactin especially in individuals wh are inclined t allergies r suffer frm asthma Aspirin shuld always be used within a safe dsage range The prpsed safe dsage range f aspirin, fr lwering the risk f certain cancers in patients wh have cnsulted with their medical practitiner, is 81mg per day The safe dsage range fr adults (in cases f fever and/r pain) is 325mg t 650mg rally r rectally every 4 hurs as needed, but intake shuld nt exceed 4g per 24 hurs It shuld nt be indiscriminately given t children and teenagers because f the risk f Reyes syndrme, allergies and pssible internal bleeding Even thugh there may be scientific evidence that aspirin is advantageus against sme nn-cmmunicable diseases like cardivascular incidents and even in lwering the risk f sme cancers, it shuld NOT be used n a cntinuus (lng-term) basis withut prir cnsultatin with a medical practitiner Medical Disclaimer This Fact Sheet and Psitin Statement is intended t prvide general infrmatin nly and, as such, shuld nt be cnsidered as a substitute fr advice, medically r therwise, cvering any specific situatin. Users shuld seek apprpriate advice befre taking r refraining frm taking any actin in reliance n any infrmatin cntained in this Fact Sheet and Psitin Statement. S far as permissible by law, the Cancer Assciatin f Researched and Authred by Prf Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupatinal Health] Apprved by Ms Elize Jubert, Chief Executive Officer [BA Scial Wrk (cum laude); MA Scial Wrk] March 2017 Page 6

7 Suth Africa (CANSA) des nt accept any liability t any persn (r his/her dependants/estate/heirs) relating t the use f any infrmatin cntained in this Fact Sheet and Psitin Statement. Whilst CANSA has taken every precautin in cmpiling this Fact Sheet and Psitin Statement, neither it, nr any cntributr(s) t this Fact Sheet and Psitin Statement can be held respnsible fr any actin (r the lack theref) taken by any persn r rganisatin wherever they shall be based, as a result, direct r therwise, f infrmatin cntained in, r accessed thrugh, this Fact Sheet and Psitin Statement. Researched and Authred by Prf Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupatinal Health] Apprved by Ms Elize Jubert, Chief Executive Officer [BA Scial Wrk (cum laude); MA Scial Wrk] March 2017 Page 7

8 Surces and References Alfns, L., Ai, G., Spitale, R.C. & Bhat, G.J Mlecular targets f aspirin and cancer preventin. Br J Cancer Jul 1;111(1):61-7. di: /bjc Epub 2014 May 29. Algra, A.M Twards a glbal brief n aspirin. The Lancet, 381: %20Lancet2013_glbal_brief_n_aspirin.pdf American Cancer Sciety Aspirin Aspirin Side Effects Bker, N.W. Aspirin: Culd it reduce yur risk fr cancer? Burke, A., Smyth, E. & FitzGerald, G. A : Analgesic antipyretic and antiinflammatry agents. Gdman and Gilman's the pharmaclgical basis f therapeutics (11 th ed.). New Yrk: McGraw-Hill. pp Drugs.cm Elwd, P.C., Mrgan, G., Pickering, J.E., Galante, J., Weightman, A.L., Mrris, D., Kelsn, M. & Dlwani, S Aspirin in the Treatment f Cancer: Reductins in Metastatic Spread and in Mrtality: A Systematic Review and Meta-Analyses f Published Studies. PLOS ONE, 2016; 11 (4): e DOI: /jurnal.pne Felix Hffman Langley, R.E. & Rthwell, P.M Aspirin in gastrintestinal nclgy: new data n an ld friend. Curr Opin Oncl Jul;26(4): di: /CCO Li, P., Cheng, R. & Zhang, S Aspirin and esphageal squamus cell carcinma: bedside t bench. Chin Med J (Engl). 2014;127(7): May Clinic MD Andersn Cancer Center Researched and Authred by Prf Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupatinal Health] Apprved by Ms Elize Jubert, Chief Executive Officer [BA Scial Wrk (cum laude); MA Scial Wrk] March 2017 Page 8

9 Nreen, F., Röösli, M., Gaj, P., Pietrzak, J., Weis, S., Urfer, P., Regula, J., Schär, P. & Truninger, K Mdulatin f age- and cancer-assciated DNA methylatin change in the healthy cln by aspirin and lifestyle. Natl Cancer Inst. Jun 28:106(7). pii: dju161. di: /jnci/dju161. Print 2014 Jul. NHS Chices.UK Pasche, B., Wang, M., Pennisn, M. & Jimenez, H Preventin and treatment f cancer with aspirin: where d we stand? Semin Oncl. Jun: 41(3): Di: /j.seminncl Epub 2014 April 24. Science Daily Su, B.B., Chen, J.H., Shi, H., Chen, Q.Q. & Wan, J Aspirin may mdify tumr micrenvirnment via antiplatelet effect. Med Hyptheses. Aug:83(2): di: /j.mehy Epub 2014 May 20. US Fd and Drug Administratin standingover-the-cuntermedicines/safedailyusefaspirin/ucm htm WebMD Wikipedia Wrld Health Organizatin Yelsengekar, A. & Mhandas, K.M Can daily aspirin help t reduce the incidence and mrtality due t cancer? Researched and Authred by Prf Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupatinal Health] Apprved by Ms Elize Jubert, Chief Executive Officer [BA Scial Wrk (cum laude); MA Scial Wrk] March 2017 Page 9