Abstract
Aspirin has been associated to a reduced risk of colorectal, and possibly of a few other common cancers. Epidemiological studies on aspirin and cancer risk published up to December 2005 have been reviewed, and pooled relative risks (RR) for several cancers have been provided. Besides a reduction in the risk of cancer of the colorectum (RR = 0.71, 95% confidence interval, CI: 0.67–0.75), there is evidence—although more limited, and mainly from case–control studies—that aspirin has a favourable effect on cancers of the esophagus (RR = 0.72, 95% CI: 0.62–0.84), stomach (RR = 0.84, 95% CI: 0.76–0.93), breast (RR = 0.91, 95% CI: 0.88–0.95), ovary (RR = 0.89, 95% CI: 0.78–1.02) and lung (RR = 0.94, 95% CI: 0.89–1.00). The role of aspirin on other cancers, such as pancreatic, prostate, bladder cancer, and non-Hodgkins’ lymphomas is less clear, and an increase of risk has been suggested for kidney cancer. For most cancer sites, however, significant heterogeneity between studies, and particularly across study design, was found, with a reduction in risk generally stronger in case–control than in cohort studies. Further, notwithstanding the large amount of epidemiological evidence, substantial uncertainties remain about the proper aspirin dose and duration of treatment.
Similar content being viewed by others
References
Berkel HJ, Holcombe RF, Middlebrooks M, Kannan K (1996) Nonsteroidal antiinflammatory drugs and colorectal cancer. Epidemiol Rev 18:205–217
Greenberg ER, Baron JA (1996) Aspirin and other nonsteroidal anti-inflammatory drugs as cancer-preventive agents. In: Stewart BW, McGregor D, Kleihies P (eds) Principles of chemoprevention. IARC Scientific Publications No. 139. International Agency for Research on Cancer, Lyon
IARC Handbooks of Cancer Prevention (1997) Non-steroidal anti-inflammatory drugs, vol 1. International Agency for Research on Cancer, Lyon
Taketo MM (1998) Cyclooxygenase-2 inhibitors in cancerogenesis (Part I). J Natl Cancer Inst 90:1529–1536
Taketo MM (1998) Cyclooxygenase-2 inhibitors in cancerogenesis (Part II). J Natl Cancer Inst 90:1609–1620
Fiorucci S, Antonelli E (2001) Cyclo-oxygenase isoenzymes. Structural basis for selective inhibition of cyclo-oxygenases by inflammatory agents. Digest Liver Dis 33:S2–S7
Thun MJ, Henley SJ, Patrono C (2002) Nonsteroidal anti-inflammatory drugs as anticancer agents: mechanistic, pharmacologic, and clinical issues. J Natl Cancer Inst 94:252–266
Bosetti C, Gallus S, La Vecchia C (2002) Aspirin and cancer risk: an update to 2001. Eur J Cancer Prev 11:535–542
González Pérez A, García Rodríguez LA, Lopez-Ridaura R (2003) Effects of non-steroidal anti-inflammatory drugs on cancer sites other than the colon and rectum: a meta-analysis. BMC Cancer 3:28
Greenland S (1987) Quantitative methods in the review of epidemiological literature. Epidemiol Rev 9:1–30
Isomäki HA, Hakulinen T, Joutsenlahti U (1978) Excess of lymphomas, leukemia, and myeloma in patients with rheumatoid arthritis. J Chron Dis 31:691–696
Gridley G, McLaughlin JK, Ekbom A, et al (1993) Incidence of cancer among patients with rheumatoid arthritis. J Natl Cancer Inst 85:307–311
Kauppi M, Pukkala E, Isomäki H (1996) Low incidence of colorectal cancer in patients with rheumatoid arthritis. Clin Exp Rheumatol 14:551–553
Friis S, Sorensen HT, McLaughlin JK, Johnsen SP, Blot WJ, Olsen JH (2003) A population-based cohort study of the risk of colorectal and other cancers among users of low-dose aspirin. Br J Cancer 88:684–688
Herendeen JM, Lindley C (2003) Use of NSAIDs for the chemoprevention of colorectal cancer. Ann Pharmacother 37:1664–1674
Kune GA, Kune S, Watson LF (1988) Colorectal cancer risk, chronic illnesses, operations, and medications: case–control results from the Melbourne colorectal cancer study. Cancer Res 48:4399–4404
Rosenberg L, Palmer JR, Zauer AG, et al (1991) A hypothesis: nonsteroidal anti-inflammatory drugs reduce the incidence of large-bowel cancer. J Natl Cancer Inst 83:355–358
Suh O, Mettlin C, Petrelli NJ (1993) Aspirin use, cancer, and polyps of the large bowel. Cancer 72:1171–1177
Muscat JE, Stellman SD, Wynder EL (1994) Nonsteroidal antiinflammatory drugs and colorectal cancer. Cancer 74:1847–1854
Peleg II, Maibach HT, Brown SH, Wilcox CM (1994) Aspirin and nonsteroidal anti-inflammatory drug use and the risk of subsequent colorectal cancer. Arch Intern Med 154:394–399
Reeves MJ, Newcomb PA, Trentham-Dietz A, Storer BE, Remington PL (1996) Nonsteroidal anti-inflammatory drug use and protection against colorectal cancer in women. Cancer Epidemiol Biomarkers Prev 5:955–960
La Vecchia C, Negri E, Franceschi S, et al (1997) Aspirin and colorectal cancer. Br J Cancer 76:675–677
Rosenberg L, Louik C, Shapiro S (1998) Nonsteroidal antiinflammatory drug use and reduced risk of large bowel carcinoma. Cancer 82:2326–2333
Friedman GD, Coates AO, Potter JD, Slattery ML (1998) Drugs and colon cancer. Pharmacoepidemiol Drug Saf 7:99–106
Neugut AI, Rosenberg DJ, Ahsan H, et al (1998) Association between coronary heart disease and cancers of the breast, prostate, and colon. Cancer Epidemiol Biomarkers Prev 7:869–873
Juarranz M, Calle-Purón ME, González-Navarro A, et al (2002) Physical exercise, use of Plantago ovata and aspirin, and reduced risk of colon cancer. Eur J Cancer Prev 11:465–472
Sansbury LB, Millikan RC, Schroeder JC, Moorman PG, North KE, Sandler RS (2005) Use of nonsteroidal antiinflammatory drugs and risk of colon cancer in a population-based, case–control study of African Americans and Whites. Am J Epidemiol 162:548–558
Paganini-Hill A, Chao A, Ross RK, Henderson BE (1989) Aspirin use and chronic diseases: a cohort study of the elderly. Br Med J 299:1247–1250
Thun MJ, Namboodiri MM, Heath CW Jr (1991) Aspirin use and reduced risk of fatal colon cancer. N Engl J Med 325:1593–1596
Thun MJ, Namboodiri MM, Calle EE, Flanders WD, Heath CW Jr (1993) Aspirin use and risk of fatal cancer. Cancer Res 53:1322–1327
Schreinemachers DM, Everson RB (1994) Aspirin use and lung, colon, and breast cancer incidence in a prospective study. Epidemiology 5:138–146
Giovannucci E, Rimm EB, Stampfer MJ, Colditz GA, Ascherio A, Willett WC (1994) Aspirin use and the risk for colorectal cancer and adenoma in male health professionals. Ann Int Med 121:241–246
Giovannucci E, Egan KM, Hunter DJ, et al (1995) Aspirin and the risk of colorectal cancer in women. N Engl J Med 333:609–614
García-Rodríguez LA, Huerta-Alvarez C (2001) Reduced risk of colorectal cancer among long-term users of aspirin and nonaspirin nonsteroidal antiinflammatory drugs. Epidemiology 12:88–93
Ratnasinghe LD, Graubard BI, Kahle L, Tangrea JA, Taylor PR, Hawk E (2004) Aspirin use and mortality from cancer in a prospective cohort study. Anticancer Res 24:3177–3184
Chan AT, Giovannucci EL, Meyerhardt JA, Schernhammer ES, Curhan GC, Fuchs CS (2005) Long-term use of aspirin and nonsteroidal anti-inflammatory drugs and risk of colorectal cancer. JAMA 294:914–923
Levi F, Lucchini F, Negri E, Boyle P, La Vecchia C (2004) Cancer mortality in Europe, 1995–1999, and an overview of trends since 1960. Int J Cancer 110:155–169
Asano TK, McLeod RS (2004) Nonsteroidal anti-inflammatory drugs and aspirin for the prevention of colorectal adenomas and cancer: a systematic review. Dis Colon Rectum 47:665–673
Greenberg ER, Baron JA, Freeman DH Jr, Mandet JS, Haile R, for the Polyp Prevention Study Group (1993) Reduced risk of large-bowel adenomas among aspirin users. The Polyp Prevention Study Group. J Natl Cancer Inst 85:912–916
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 348:883–890
Baron JA, Cole BF, Sandler RS, Haile RW, et al (2003) A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med 348:891–899
Benamouzig R, Deyra J, Martin A, et al (2003) Daily soluble aspirin and prevention of colorectal adenoma recurrence: one-year results of the APACC trial. Gastroenterology 125:328–336
Gann PH, Manson JE, Glynn RJ, Buring JE, Hennekens CH (1993) Low-dose aspirin and incidence of colorectal cancers in a randomized trial. J Natl Cancer Inst 85:1220–1224
Stürmer T, Glynn RJ, Lee I-M, Manson JE, Buring JE, Hennekens CH (1998) Aspirin use and colorectal cancer: post-trial follow-up data from the Physicians’ Health Study. Ann Intern Med 128:713–720
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
Derry S, Loke YK (2000) Risk of gastrointestinal haemorrhage with long term use of aspirin: meta-analysis. BMJ 321:1183–1187
Farrow DC, Vaughan TL, Hansten PD, et al (1998) Use of aspirin and other nonsteroidal anti-inflammatory drugs and risk of esophageal and gastric cancer. Cancer Epidemiol Biomarkers Prev 7:97–102
Sharp L, Chilvers CE, Cheng KK, et al (2001) Risk factors for squamous cell carcinoma of the esophagus in women: a case–control study. Br J Cancer 85:1667–1670
Funkhouser EM, Sharp GB (1995) Aspirin and reduced risk of esophageal carcinoma. Cancer 76:1116–1119
Lindblad M, Lagergren J, García Rodríguez LA (2005) Nonsteroidal anti-inflammatory drugs and risk of esophageal and gastric cancer. Cancer Epidemiol Biomarkers Prev 14:444–450
Zaridze D, Borisova E, Maximovitch D, Chkhikvadze V (1999) Aspirin protects against gastric cancer: results of a case–control study from Moscow, Russia. Int J Cancer 82:473–476
Akre K, Ekstrom AM, Signorello LB, Hansson LE, Nyren O (2001) Aspirin and risk for gastric cancer: a population-based case–control study in Sweden. Br J Cancer 84:965–968
Menezes RJ, Huber KR, Mahoney MC, Moysich KB (2002) Regular use of aspirin and pancreatic cancer risk. BMC Public Health 2:18
Anderson KE, Johnson TW, Lazovich D, Folsom AR (2002) Association between nonsteroidal anti-inflammatory drug use and the incidence of pancreatic cancer. J Natl Cancer Inst 94:1168–1171
Schernhammer ES, Kang JH, Chan AT, et al (2004) A prospective study of aspirin use and the risk of pancreatic cancer in women. J Natl Cancer Inst 96:22–28
Jacobs EJ, Connell CJ, Rodriguez C, Patel AV, Calle EE, Thun MJ (2004) Aspirin use and pancreatic cancer mortality in a large United States cohort. J Natl Cancer Inst 96:524–528
Corley DA, Kerlikowske K, Verma R, Buffler P (2003) Protective association of aspirin/NSAIDs and esophageal cancer: a systematic review and meta-analysis. Gastroenterology 124:47–56
Wang WH, Huang JQ, Zheng GF, Lam SK, Karlberg J, Wong BC (2003) Non-steroidal anti-inflammatory drug use and the risk of gastric cancer: a systematic review and meta-analysis. J Natl Cancer Inst 95:1784–1791
Bosetti C, Talamini R, Franceschi S, Negri E, Garavello W, La Vecchia C (2003) Aspirin use and cancers of the upper aerodigestive tract. Br J Cancer 88:672–674
Moysich KB, Menezes RJ, Ronsani A, et al (2002) Regular aspirin use and lung cancer risk. BMC Cancer 2:31
Muscat JE, Chen SQ, Richie JP Jr, et al (2003) Risk of lung carcinoma among users of nonsteroidal antiinflammatory drugs. Cancer 97:1732–1736
Akhmedkhanov A, Toniolo P, Zeleniuch-Jacquotte A, Koenig KL, Shore RE (2002) Aspirin and lung cancer in women. Br J Cancer 87:49–53
Holick CN, Michaud DS, Leitzmann MF, Willett WC, Giovannucci E (2003) Aspirin use and lung cancer in men. Br J Cancer 89:1705–1708
Harris RE, Namboodiri KK, Farrar WB (1996) Nonsteroidal antiinflammatory drugs and breast cancer. Epidemiology 7:203–205
Coogan PF, Rao SR, Rosenberg L, et al (1999) The relationship of nonsteroidal anti-inflammatory drug use to the risk of breast cancer. Prev Med 29:72–76
Cotterchio M, Kreiger N, Sloan M, Steingart A (2001) Nonsteroidal anti-inflammatory drug use and breast cancer risk. Cancer Epidemiol Biomarkers Prev 10:1213–1217
Terry MB, Gammon MD, Zhang FF, et al (2004) Association of frequency and duration of aspirin use and hormone receptor status with breast cancer risk. JAMA 291:2433–2440
Swede H, Mirand AL, Menezes RJ, Moysich KB (2005) Association of regular aspirin use and breast cancer risk. Oncology 68:40–47
Zhang Y, Coogan PF, Palmer JR, Strom BL, Rosenberg L (2005) Use of nonsteroidal antiinflammatory drugs and risk of breast cancer: the Case–control Surveillance Study revisited. Am J Epidemiol 162:165–170
Friedman GD, Ury HK (1980) Initial screening for carcinogenicity of commonly used drugs. J Natl Cancer Inst 85:723–733
Egan KM, Stampfer MJ, Giovannucci E, Rosner BA, Colditz GA (1996) Prospective study of regular aspirin use and the risk of breast cancer. J Natl Cancer Inst 88:988–993
Harris RE, Kasbari S, Farrar WB (1999) Prospective study of nonsteroidal anti-inflammatory drugs and breast cancer. Oncol Rep 6:71–73
Johnson TW, Anderson KE, Lazovich D, Folsom AR (2002) Association of aspirin and nonsteroidal anti-inflammatory drug use with breast cancer. Cancer Epidemiol Biomarkers Prev 11:1586–1591
Harris RE, Chlebowski RT, Jackson RD, et al. (2003) Breast cancer and nonsteroidal anti-inflammatory drugs: prospective results from the Women’s Health Initiative. Cancer Res 63:6096–6101
García Rodríguez LA, González Pérez A (2004) Risk of breast cancer among users of aspirin and other anti-inflammatory drugs. Br J Cancer 91:525–529
Jacobs EJ, Thun MJ, Connell CJ, et al (2005) Aspirin and other nonsteroidal anti-inflammatory drugs and breast cancer incidence in a large U.S. cohort. Cancer Epidemiol Biomarkers Prev 14:261–264
Marshall SF, Bernstein L, Anton-Culver H, et al (2005) Nonsteroidal anti-inflammatory drug use and breast cancer risk by stage and hormone receptor status. J Natl Cancer Inst 97:805–812
Tzonou A, Polychronopoulou A, Hsieh CC, Rebelakos A, Karakatsani A, Trichopoulos D (1993) Hair dyes, analgesics, tranquilizers and perineal talc application as risk factors for ovarian cancer. Int J Cancer 55:408–410
Cramer DW, Harlow BL, Titus-Ernstoff L, Bohlke K, Welch WR, Greenberg ER (1998) Over-the-counter analgesics and risk of ovarian cancer. Lancet 351:104–107
Tavani A, Gallus S, La Vecchia C, Conti E, Montella M, Franceschi S (2000) Aspirin and ovarian cancer: an Italian case–control study. Ann Oncol 11:1171–1173
Rosenberg L, Palmer JR, Rao RS, et al (2000) A case–control study of analgesic use and ovarian cancer. Cancer Epidemiol Biomarkers Prev 9:933–937
Moysich KB, Mettlin C, Piver MS, Natarajan N, Menezes RJ, Swede H (2001) Regular use of analgesic drugs and ovarian cancer risk. Cancer Epidemiol Biomarkers Prev 10:903–906
Akhmedkhanov A, Toniolo P, Zeleniuch-Jacquotte A, Kato I, Koenig KL, Shore RE (2001) Aspirin and epithelial ovarian cancer. Prev Med 33:682–687
Fairfield KM, Hunter DJ, Fuchs CS, Colditz GA, Hankinson SE (2002) Aspirin, other NSAIDs, and ovarian cancer risk (United States). Cancer Causes Control 13:535–342
Lacey JV Jr, Sherman ME, Hartge P, Schatzkin A, Schairer C (2004) Medication use and risk of ovarian carcinoma: a prospective study. Int J Cancer 108:281–286
Khuder SA, Mutgi AB (2001) Breast cancer and NSAID use: a meta-analysis. Br J Cancer 84:1188–1192
Goss PE, Ingle JN, Martino S, et al (2003) A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med 349:1793–1802
Ness RB, Cottreau C (1999) Possible role of ovarian epithelial inflammation in ovarian cancer. J Natl Cancer Inst 91:1459–1467
Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow? Lancet 357:359–345
Norrish AE, Jackson RT, McRae CU (1998) Non-steroidal anti-inflammatory drugs and prostate cancer progression. Int J Cancer 77:511–515
Menezes RJ, Swede H, Mettlin C, Moysich KB (2002) Regular aspirin use and risk of prostate cancer. Proceedings of the American association for cancer research annual meeting. San Francisco, USA 43:933
Irani J, Ravery V, Pariente JL, et al (2002) Effect of nonsteroidal anti-inflammatory agents and finasteride on prostate cancer risk. J Urol 168:1985–1988
Bosetti C, Talamini R, Negri E, Franceschi S, Montella M, La Vecchia C (2006) Aspirin and the risk of prostate cancer. Eur J Cancer Prev 15:43–45
Leitzmann MF, Stampfer MJ, Ma J, et al (2002) Aspirin use in relation to risk of prostate cancer. Cancer Epidemiol Biomarkers Prev 11:1108–1111
Habel LA, Zhao W, Stanford JL (2002) Daily aspirin use and prostate cancer risk in a large, multiracial cohort in the US. Cancer Causes Control 13:427–434
Perron L, Bairati I, Moore L, Meyer F (2003) Dosage, duration and timing of nonsteroidal antiinflammatory drug use and risk of prostate cancer. Int J Cancer 106:409–415
García Rodríguez LA, González Pérez A (2004) Inverse association between nonsteroidal anti-inflammatory drugs and prostate cancer. Cancer Epidemiol Biomarkers Prev 13:649–653
Platz EA, Rohrmann S, Pearson JD, et al (2005) Nonsteroidal anti-inflammatory drugs and risk of prostate cancer in the Baltimore Longitudinal Study of Aging. Cancer Epidemiol Biomarkers Prev 14:390–396
Jacobs EJ, Rodriguez C, Mondul AM, et al (2005) A large cohort study of aspirin and other nonsteroidal anti-inflammatory drugs and prostate cancer incidence. J Natl Cancer Inst 97:975–980
Mahmud S, Franco E, Aprikian A (2004) Prostate cancer and use of nonsteroidal anti-inflammatory drugs: systematic review and meta-analysis. Br J Cancer 90:93–99
Castelao JE, Yuan JM, Gago-Dominguez M, Yu MC, Ross RK (2000) Non-steroidal anti-inflammatory drugs and bladder cancer prevention. Br J Cancer 82:1364–1369
McLaughlin JK, Blot WJ, Mehl ES, Fraumeni JF (1985) Relation of analgesic use to renal cancer: population-based findings. Natl Cancer Inst Monogr 69:217–222
McCredie M, Ford JM, Stewart JH (1988) Risk factors for cancer of the renal parenchyma. Int J Cancer 42:13–16
Mellemgaard A, Niwa S, Mehl ES, Engholm G, McLaughlin JK, Olsen JH (1994) Risk factors for renal cell carcinoma in Denmark: role of medication and medical history. Int J Epidemiol 23:923–930
McCredie M, Pommer W, McLaughlin JK, et al (1995) International renal-cell cancer study. II. Analgesics. Int J Cancer 60:345–349
Gago-Dominguez M, Yuan JM, Castelao JE, Ross RK, Yu MC (1999) Regular use of analgesics is a risk factor for renal cell carcinoma. Br J Cancer 81:542–548
IARC Working Group on the Evaluation of Carcinogenic Risks to Humans (1987) IARC monographs on the evaluation of carcinogenic risks to humans. Overall evaluations of carcinogenicity: an updating of IARC monographs, vols 1 to 42. Suppl. 7. International Agency for Research on Cancer, Lyon
Bernstein L, Ross RK (1992) Prior medication use and health history as risk factors for non-Hodgkin’s lymphoma: preliminary results from a case–control study in Los Angeles County. Cancer Res 52:5510s–5515s
Kato I, Koenig KL, Shore RE, et al (2002) Use of anti-inflammatory and non-narcotic analgesic drugs and risk of non-Hodgkin’s lymphoma (NHL) (United States). Cancer Causes Control 13:965–974
Zhang Y, Holford TR, Leaderer B, et al (2004) Prior medical conditions and medication use and risk of non-Hodgkin lymphoma in Connecticut United States women. Cancer Causes Control 15:419–428
Chang ET, Zheng T, Weir EG, et al (2004) Aspirin and the risk of Hodgkin’s lymphoma in a population-based case–control study. J Natl Cancer Inst 96:305–315
Baker JA, Weiss JR, Czuczman MS, Menezes RJ, Ambrosone CB, Moysich KB (2005) Regular use of aspirin or acetaminophen and risk of non-Hodgkin lymphoma. Cancer Causes Control 16:301–308
Cerhan JR, Anderson KE, Janney CA, Vachon CM, Witzig TE, Habermann TM (2003) Association of aspirin and other non-steroidal anti-inflammatory drug use with incidence of non-Hodgkin lymphoma. Int J Cancer 106:784–788
Kasum CM, Blair CK, Folsom AR, Ross JA (2003) Non-steroidal anti-inflammatory drug use and risk of adult leukemia. Cancer Epidemiol Biomarkers Prev 12:534–537
Signorello LB, McLaughlin JK, Lipworth L, Friis S, Sorensen HT, Blot WJ (2003) Confounding by indication: implications for implant research. J Long Term Eff Med Implants 13:63–68
Acknowledgment
The authors thank Mrs I. Garimoldi for editorial assistance.
Author information
Authors and Affiliations
Corresponding author
Additional information
This work was conducted with the contribution of the Italian Association for Cancer Research, the Italian League Against Cancer, and the Italian Ministry of Education (PRIN 2005).
Rights and permissions
About this article
Cite this article
Bosetti, C., Gallus, S. & La Vecchia, C. Aspirin and cancer risk: an updated quantitative review to 2005. Cancer Causes Control 17, 871–888 (2006). https://doi.org/10.1007/s10552-006-0033-7
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s10552-006-0033-7