Aspirin, nonsteroidal anti-inflammatory drugs, paracetamol and risk of endometrial cancer: A case–control study, systematic review and meta-analysis
Corresponding Author
Annette S. Neill
Queensland Institute of Medical Research, Genetics and Population Health Division, Herston, Brisbane, Australia
The University of Queensland, School of Population Health, Herston, Brisbane, Australia
Tel.: +61-7-33620281, Fax: +61-7-38453503
Queensland Institute of Medical Research, Genetics and Population Health Division, 300 Herston Road, Herston, Brisbane 4006, AustraliaSearch for more papers by this authorChristina M. Nagle
Queensland Institute of Medical Research, Genetics and Population Health Division, Herston, Brisbane, Australia
Search for more papers by this authorMelinda M. Protani
Queensland Institute of Medical Research, Genetics and Population Health Division, Herston, Brisbane, Australia
Search for more papers by this authorAndreas Obermair
Queensland Centre for Gynaecological Oncology, Royal Brisbane and Women's Hospital, Herston, Brisbane, Australia
Search for more papers by this authorAmanda B. Spurdle
Queensland Institute of Medical Research, Genetics and Population Health Division, Herston, Brisbane, Australia
Search for more papers by this authorPenelope M. Webb
Queensland Institute of Medical Research, Genetics and Population Health Division, Herston, Brisbane, Australia
The ANECS Group comprises Spurdle A.B., Webb P., Young J. (Queensland Institute of Medical Research); Consumer representative: McQuire L.; Clinical Collaborators: NSW: Baron-Hay S., Bell D., Bonaventura A., Brand A., Braye S., Carter J., Chan F., Dalrymple C., Ferrier A. (deceased), Gard G., Hacker N., Hogg R., Houghton R., Marsden D., McIlroy K., Otton G., Pather S., Proietto A., Robertson G., Scurry J., Sharma R., Wain G., Wong F.; Qld: Armes J., Crandon A., Cummings M., Land R., Nicklin J., Perrin L., Obermair A., Ward B.; SA: Davy M., Dodd T., Miller J., Oehler M., Paramasivum S., Pierides J., Whitehead F.; Tas: Blomfield P., Challis D.; Vic: Neesham D., Pyman J., Quinn M., Rome R., Weitzer M.; WA: Brennan B., Hammond I., Leung Y., McCartney A. (deceased), Stewart C., Thompson J.; Project Managers: O'Brien S., Moore S.; Laboratory Manager: Ferguson K.; Pathology Support: Walsh M.; Admin Support: Cicero R., Green L., Griffith J., Jackman L., Ranieri B.; Laboratory Assistants: O'Brien M., Schultz P.; Research Nurses: Alexander B., Baxter C., Croy H., Fitzgerald A., Herron E., Hill C., Jones M., Maidens J., Marshall A., Martin K., Mayhew J., Minehan E., Roffe D., Shirley H., Steane H., Stenlake A., Ward A., Webb S., White J.
Search for more papers by this authorfor the Australian National Endometrial Cancer Study Group
Search for more papers by this authorCorresponding Author
Annette S. Neill
Queensland Institute of Medical Research, Genetics and Population Health Division, Herston, Brisbane, Australia
The University of Queensland, School of Population Health, Herston, Brisbane, Australia
Tel.: +61-7-33620281, Fax: +61-7-38453503
Queensland Institute of Medical Research, Genetics and Population Health Division, 300 Herston Road, Herston, Brisbane 4006, AustraliaSearch for more papers by this authorChristina M. Nagle
Queensland Institute of Medical Research, Genetics and Population Health Division, Herston, Brisbane, Australia
Search for more papers by this authorMelinda M. Protani
Queensland Institute of Medical Research, Genetics and Population Health Division, Herston, Brisbane, Australia
Search for more papers by this authorAndreas Obermair
Queensland Centre for Gynaecological Oncology, Royal Brisbane and Women's Hospital, Herston, Brisbane, Australia
Search for more papers by this authorAmanda B. Spurdle
Queensland Institute of Medical Research, Genetics and Population Health Division, Herston, Brisbane, Australia
Search for more papers by this authorPenelope M. Webb
Queensland Institute of Medical Research, Genetics and Population Health Division, Herston, Brisbane, Australia
The ANECS Group comprises Spurdle A.B., Webb P., Young J. (Queensland Institute of Medical Research); Consumer representative: McQuire L.; Clinical Collaborators: NSW: Baron-Hay S., Bell D., Bonaventura A., Brand A., Braye S., Carter J., Chan F., Dalrymple C., Ferrier A. (deceased), Gard G., Hacker N., Hogg R., Houghton R., Marsden D., McIlroy K., Otton G., Pather S., Proietto A., Robertson G., Scurry J., Sharma R., Wain G., Wong F.; Qld: Armes J., Crandon A., Cummings M., Land R., Nicklin J., Perrin L., Obermair A., Ward B.; SA: Davy M., Dodd T., Miller J., Oehler M., Paramasivum S., Pierides J., Whitehead F.; Tas: Blomfield P., Challis D.; Vic: Neesham D., Pyman J., Quinn M., Rome R., Weitzer M.; WA: Brennan B., Hammond I., Leung Y., McCartney A. (deceased), Stewart C., Thompson J.; Project Managers: O'Brien S., Moore S.; Laboratory Manager: Ferguson K.; Pathology Support: Walsh M.; Admin Support: Cicero R., Green L., Griffith J., Jackman L., Ranieri B.; Laboratory Assistants: O'Brien M., Schultz P.; Research Nurses: Alexander B., Baxter C., Croy H., Fitzgerald A., Herron E., Hill C., Jones M., Maidens J., Marshall A., Martin K., Mayhew J., Minehan E., Roffe D., Shirley H., Steane H., Stenlake A., Ward A., Webb S., White J.
Search for more papers by this authorfor the Australian National Endometrial Cancer Study Group
Search for more papers by this authorAbstract
Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with reduced risk of a number of cancer types, however, previous studies of endometrial cancer have yielded inconclusive results. We analyzed data from the Australian National Endometrial Cancer Study (ANECS), a population-based case–control study (1,398 cases, 740 controls). We systematically reviewed all the evidence linking aspirin/NSAIDs use with endometrial cancer and conducted a meta-analysis. For ANECS, unconditional logistic regression was used to estimate odds ratios (OR) adjusting for potential confounders. For the systematic review, we searched Pubmed, Embase, Web of Science and conducted a review of citations from retrieved articles. The meta-analysis risk estimates were pooled using a random-effects model. In our case–control study, women who had ever used aspirin in the last 5 years had a significantly lower risk of endometrial cancer OR = 0.78 [95% confidence interval (CI): 0.63-0.97]. There was a significant inverse dose–response (p-trend <0.001) such that women who reported using ≥2 aspirin/week had almost half the risk OR = 0.54 (0.38–0.78). No significant associations were observed between use of half-aspirin/day, non-aspirin NSAIDs or paracetamol and endometrial cancer risk. The results were similar when examined by cancer subtype. Nine studies were included in the meta-analysis. The overall pooled risk estimate for any versus no use of aspirin was 0.87 (0.79–0.96) with no evidence of heterogeneity. The pooled risk estimate for obese women (BMI ≥ 30 kg/m2) was 0.72 (0.58–0.90) but there was no association for non-obese women. Overall these results suggest that aspirin may reduce the risk of endometrial cancer, particularly among obese women.
Abstract
What's new?
The authors report that aspirin may reduce the risk of endometrial cancer by as much as half, particularly among obese women. Similar results were not observed for non-aspirin NSAIDs or paracetamol (acetaminophen). This may be because aspirin can influence cellular processes such as apoptosis and angiogenesis, which are crucial for the development and growth of malignancies.
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References
- 1 Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127: 2893–917.
- 2 Dossus L, Allen N, Kaaks R, et al. Reproductive risk factors and endometrial cancer: the European Prospective Investigation into Cancer and Nutrition. Int J Cancer 2009; 127: 442–51.
- 3 Purdie DM, Green AC. Epidemiology of endometrial cancer. Best Pract Res Clin Obstet Gynaecol 2001; 15: 341–54.
- 4 Modugno F, Ness RB, Chen C, et al. Inflammation and endometrial cancer: a hypothesis. Cancer Epidemiol Biomarkers Prev 2005; 14: 2840–7.
- 5 Wallace AE, Gibson DA, Saunders PT, et al. Inflammatory events in endometrial adenocarcinoma. J Endocrinol 2010; 206: 141–57.
- 6 O'Byrne KJ, Dalgleish AG. Chronic immune activation and inflammation as the cause of malignancy. Br J Cancer 2001; 85: 473–83.
- 7 Dubois RN, Abramson SB, Crofford L, et al. Cyclooxygenase in biology and disease. FASEB J 1998; 12: 1063–73.
- 8 Ghosh N, Chaki R, Mandal V, et al. COX-2 as a target for cancer chemotherapy. Pharmacol Rep 2010; 62: 233–44.
- 9 Langley RE, Burdett S, Tierney JF, et al. Aspirin and cancer: has aspirin been overlooked as an adjuvant therapy? Br J Cancer 2011; 105: 1107–13.
- 10 Cuzick J, Otto F, Baron JA, et al. Aspirin and non-steroidal anti-inflammatory drugs for cancer prevention: an international consensus statement. The lancet oncology 2009; 10: 501–7.
- 11 Bosetti C, Bravi F, Talamini R, et al. Aspirin and risk of endometrial cancer: a case-control study from Italy. Eur J Cancer Prev 2010; 19: 401–3.
- 12 Danforth KN, Gierach GL, Brinton LA, et al. Nonsteroidal anti-inflammatory drug use and endometrial cancer risk in the NIH-AARP Diet and Health Study. Cancer Prev Res (Phila) 2009; 2: 466–72.
- 13 Fortuny J, Sima C, Bayuga S, et al. Risk of endometrial cancer in relation to medical conditions and medication use. Cancer Epidemiol Biomarkers Prev 2009; 18: 1448–56.
- 14 Moysich KB, Baker JA, Rodabaugh KJ, et al. Regular analgesic use and risk of endometrial cancer. Cancer Epidemiol Biomarkers Prev 2005; 14: 2923–8.
- 15 Prizment AE, Folsom AR, Anderson KE. Nonsteroidal anti-inflammatory drugs and risk for ovarian and endometrial cancers in the Iowa Women's Health Study. Cancer Epidemiol Biomarkers Prev 2010; 19: 435–42.
- 16 Schreinemachers DM, Everson RB. Aspirin use and lung, colon, and breast cancer incidence in a prospective study. Epidemiology 1994; 5: 138–46.
- 17 Bodelon C, Doherty JA, Chen C, et al. Use of nonsteroidal antiinflammatory drugs and risk of endometrial cancer. Am J Epidemiol 2009; 170: 1512–7.
- 18 Viswanathan AN, Feskanich D, Schernhammer ES, et al. Aspirin, NSAID, and acetaminophen use and the risk of endometrial cancer. Cancer Res 2008; 68: 2507–13.
- 19 Botting RM. Mechanism of action of acetaminophen: is there a cyclooxygenase 3? Clin Infect Dis 2000; 31( Suppl 5): S202–10.
- 20 Silverberg S, Kurman, RJ, Nogales F, et al. Tumours of the uterine corpus. In: F Tavassoli, P Devilee, eds. World Health Organization Classification of Tumours. Pathology and genetics of tumours of the breast and female genital organs. Lyon: IRAC Press, 2003.
- 21 Cleophas TJ, Zwinderman AH. Random effects models in clinical research. Int J Clin Pharmacol Ther 2008; 46: 421–7.
- 22 UBM Medica Australia. MIMS Abbreviated Prescribing Information. St Leonards, NSW: MIMS Australia, 1996–2010.
- 23 Cook NR, Lee IM, Gaziano JM, et al. Low-dose aspirin in the primary prevention of cancer: the Women's Health Study: a randomized controlled trial. JAMA 2005; 294: 47–55.
- 24 Rothwell PM, Wilson M, Elwin CE, et al. Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet 2010; 376: 1741–50.
- 25 Harvey AE, Lashinger LM, Hursting SD. The growing challenge of obesity and cancer: an inflammatory issue. Ann N Y Acad Sci 2011; 1229: 45–52.
- 26 Simmons DL, Botting RM, Hla T. Cyclooxygenase isozymes: the biology of prostaglandin synthesis and inhibition. Pharmacol Rev 2004; 56: 387–437.
- 27 Arango HA, Icely S, Roberts WS, et al. Aspirin effects on endometrial cancer cell growth. Obstet Gynecol 2001; 97: 423–7.
- 28 Gao J, Niwa K, Sun W, et al. Non-steroidal anti-inflammatory drugs inhibit cellular proliferation and upregulate cyclooxygenase-2 protein expression in endometrial cancer cells. Cancer Sci 2004; 95: 901–7.
- 29 Bardia A, Olson JE, Vachon CM, et al. Effect of aspirin and other NSAIDs on postmenopausal breast cancer incidence by hormone receptor status: results from a prospective cohort study. Breast Cancer Res Treat 2011; 126: 149–55.
- 30 Gierach GL, Lacey JV, Jr, Schatzkin A, et al. Nonsteroidal anti-inflammatory drugs and breast cancer risk in the National Institutes of Health-AARP Diet and Health Study. Breast Cancer Res 2008; 10: R38.
- 31 Mahmud SM, Franco EL, Aprikian AG. Use of nonsteroidal anti-inflammatory drugs and prostate cancer risk: a meta-analysis. Int J Cancer 2010; 127: 1680–91.
- 32 Jacobs EJ, Rodriguez C, Mondul AM, et al. A large cohort study of aspirin and other nonsteroidal anti-inflammatory drugs and prostate cancer incidence. J Natl Cancer Inst 2005; 97: 975–80.
- 33 Akhmedkhanov A, Toniolo P, Zeleniuch-Jacquotte A, et al. Aspirin and lung cancer in women. Br J Cancer 2002; 87: 49–53.
- 34 Oh SW, Myung SK, Park JY, et al. Aspirin use and risk for lung cancer: a meta-analysis. Ann Oncol 2011; 22: 2456–65.
- 35 Abnet CC, Freedman ND, Kamangar F, et al. Non-steroidal anti-inflammatory drugs and risk of gastric and oesophageal adenocarcinomas: results from a cohort study and a meta-analysis. Br J Cancer 2009; 100: 551–7.
- 36 Tian W, Zhao Y, Liu S, et al. Meta-analysis on the relationship between nonsteroidal anti-inflammatory drug use and gastric cancer. Eur J Cancer Prev 2010; 19: 288–98.
- 37 Corley DA, Kerlikowske K, Verma R, et al. Protective association of aspirin/NSAIDs and esophageal cancer: a systematic review and meta-analysis. Gastroenterology 2003; 124: 47–56.
- 38 Sadeghi S, Bain CJ, Pandeya N, et al. Aspirin, nonsteroidal anti-inflammatory drugs, and the risks of cancers of the esophagus. Cancer Epidemiol Biomarkers Prev 2008; 17: 1169–78.
- 39 Tan XL, Reid-Lombardo KM, Bamlet WR, et al. Aspirin, nonsteroidal anti-inflammatory drugs (NSAID), acetaminophen, and pancreatic cancer risk: a clinic-based case-control study. Cancer Prev Res (Phila) 2011; 4: 1835–41.
- 40 Curiel-Lewandrowski C, Nijsten T, Gomez ML, et al. Long-term use of nonsteroidal anti-inflammatory drugs decreases the risk of cutaneous melanoma: results of a United States case-control study. J Invest Dermatol 2011; 131: 1460–8.
- 41 Cheema AA. Should people on aspirin avoid Ibuprofen? A review of the literature. Cardiol Rev 2004; 12: 174–6.
- 42 Jankowski JA, Limburg PJ. Aspirin therapy for cancer: it is never too late. Br J Cancer 2011; 105: 1105–6.
- 43 Rostom A, Dube C, Lewin G. Use of aspirin and NSAIDs to prevent colorectal cancer: an evidence synthesis prepared for the agency for healthcare research and quality by the University of Ottawa evidence-based practice center at the University of Ottawa, Ottawa Canada, under Contract No. 290-02-0021. AHRQ Publication No. 07–0596-EF-1. Rockville, Maryland: Agency for Healthcare Research and Quality, 2007.
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