Non‐steroidal anti‐inflammatory drugs and cancer risk in women: Results from the Women's Health Initiative

The use of non‐steroidal anti‐inflammatory drugs (NSAIDs) has been associated with reduced risks of cancers at several sites in some studies; however, we recently reported no association between their use and total cancer risk in women in a prospective study. Here we examine the association between NSAIDs and total and site‐specific cancer incidence in the large, prospective Women's Health Initiative (WHI). Women (129,013) were recruited to participate in the WHI at 40 US clinical centers from 1993 to 1998 and followed prospectively. After 9.7 years of follow‐up, 12,998 incident, first primary, invasive cancers were diagnosed. NSAID use was systematically collected at study visits. We used Cox proportional hazards regression models to estimate multivariable‐adjusted hazard ratios (HR) and 95% confidence intervals (CI) for associations between NSAIDs use and total and site‐specific cancer risk. Relative to non‐use, consistent use (i.e., use at baseline and year 3 of follow‐up) of any NSAID was not associated with total cancer risk (HR 1.00, 95% CI: 0.94–1.06). Results for individual NSAIDs were similar to the aggregate measure. In site‐specific analyses, NSAIDs were associated with reduced risks of colorectal cancer, ovarian cancer, and melanoma. Our study confirms a chemopreventive benefit for colorectal cancer in women and gives preliminary evidence for a reduction of the risk of some rarer cancers. NSAIDs' benefit on cancer risk was therefore limited to specific sites and not evident when total cancer risk was examined. This information may be of importance when NSAIDs are considered as chemopreventive agents.

[1]  J. Cerhan,et al.  Association of aspirin and nonaspirin nonsteroidal anti-inflammatory drugs with cancer incidence and mortality. , 2007, Journal of the National Cancer Institute.

[2]  N. Cook,et al.  Alternate-Day, Low-Dose Aspirin and Cancer Risk: Long-Term Observational Follow-up of a Randomized Trial , 2013, Annals of Internal Medicine.

[3]  E. Feuer,et al.  SEER Cancer Statistics Review, 1975-2003 , 2006 .

[4]  J. Y. Park,et al.  Aspirin use and risk for lung cancer: a meta-analysis. , 2011, Annals of oncology : official journal of the European Society for Medical Oncology.

[5]  J. Meyerhardt,et al.  Long-term use of aspirin and nonsteroidal anti-inflammatory drugs and risk of colorectal cancer. , 2005, JAMA.

[6]  R. Chlebowski,et al.  The Women's Health Initiative Dietary Modification trial: overview and baseline characteristics of participants. , 2003, Annals of epidemiology.

[7]  H T Sørensen,et al.  Risk of cancer in a large cohort of nonaspirin NSAID users: a population-based study , 2003, British Journal of Cancer.

[8]  Shan Li,et al.  Association between non-steroidal anti-inflammatory drug use and melanoma risk: a meta-analysis of 13 studies , 2013, Cancer Causes & Control.

[9]  P. Rothwell,et al.  Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials , 2012, The Lancet.

[10]  A. LaCroix,et al.  The Women's Health Initiative calcium-vitamin D trial: overview and baseline characteristics of participants. , 2003, Annals of epidemiology.

[11]  J. Potter,et al.  Non-steroidal anti-inflammatory drugs and cancer incidence by sex in the VITamins And Lifestyle (VITAL) cohort , 2012, Cancer Causes & Control.

[12]  Garnet L Anderson,et al.  The Women's Health Initiative recruitment methods and results. , 2003, Annals of epidemiology.

[13]  J. Cuzick,et al.  Aspirin and cancer risk: a quantitative review to 2011. , 2012, Annals of oncology : official journal of the European Society for Medical Oncology.

[14]  Martin Krapcho,et al.  SEER Cancer Statistics Review, 1975–2009 (Vintage 2009 Populations) , 2012 .

[15]  JoAnn E. Manson,et al.  Design of the Women's Health Initiative clinical trial and observational study. The Women's Health Initiative Study Group. , 1998, Controlled clinical trials.

[16]  R. DuBois,et al.  The role of COX-2 in intestinal inflammation and colorectal cancer , 2010, Oncogene.

[17]  J. Gaziano,et al.  Low-Dose Aspirin in the Primary Prevention of Cancer. The Women’s Health Study: A Randomized Controlled Trial , 2005 .

[18]  Vilmundur Gudnason,et al.  C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. , 2004, The New England journal of medicine.

[19]  Scott Davis,et al.  Implementation of the Women's Health Initiative study design. , 2003, Annals of epidemiology.

[20]  P. Rothwell,et al.  Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials , 2011, The Lancet.

[21]  S. Hankinson,et al.  Analgesic Use and Sex Steroid Hormone Concentrations in Postmenopausal Women , 2010, Cancer Epidemiology, Biomarkers & Prevention.

[22]  J. Baron,et al.  Aspirin for the chemoprevention of colorectal adenomas: meta-analysis of the randomized trials. , 2009, Journal of the National Cancer Institute.

[23]  V. McCormack,et al.  Aspirin and NSAID use and lung cancer risk: a pooled analysis in the International Lung Cancer Consortium (ILCCO) , 2011, Cancer Causes & Control.

[24]  A. Algra,et al.  Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials , 2010, The Lancet.

[25]  C. Shapiro,et al.  Translational studies on aromatase, cyclooxygenases, and enzyme inhibitors in breast cancer , 2005, The Journal of Steroid Biochemistry and Molecular Biology.

[26]  S. Ogino,et al.  Aspirin Use and Survival After Diagnosis of Colorectal Cancer , 2009 .

[27]  Susan R. Johnson,et al.  The Women's Health Initiative postmenopausal hormone trials: overview and baseline characteristics of participants. , 2003, Annals of epidemiology.

[28]  T. Luo,et al.  Aspirin use and breast cancer risk: a meta-analysis , 2011, Breast Cancer Research and Treatment.

[29]  G. Anderson,et al.  Migraine History, Nonsteroidal Anti-inflammatory Drug Use, and Risk of Postmenopausal Endometrial Cancer , 2012, Hormones and Cancer.

[30]  R. Langer,et al.  The Women's Health Initiative Observational Study: baseline characteristics of participants and reliability of baseline measures. , 2003, Annals of epidemiology.

[31]  F. Cicuttini,et al.  Associations between serum levels of inflammatory markers and change in knee pain over 5 years in older adults: a prospective cohort study , 2012, Annals of the rheumatic diseases.

[32]  A. Spurdle,et al.  Aspirin, nonsteroidal anti‐inflammatory drugs, paracetamol and risk of endometrial cancer: A case–control study, systematic review and meta‐analysis , 2013, International journal of cancer.

[33]  G. Anderson,et al.  Breast cancer and nonsteroidal anti-inflammatory drugs: prospective results from the Women's Health Initiative. , 2003, Cancer research.

[34]  J. Olsen,et al.  A population-based cohort study of the risk of colorectal and other cancers among users of low-dose aspirin , 2003, British Journal of Cancer.

[35]  C. Ulrich,et al.  Correlates of circulating C-reactive protein and serum amyloid A concentrations in breast cancer survivors , 2009, Breast Cancer Research and Treatment.

[36]  M. Banach,et al.  The influence of atorvastatin on parameters of inflammation and function of the left ventricle in patients with dilated cardiomyopathy. , 2009, Medical science monitor : international medical journal of experimental and clinical research.

[37]  S. Friis,et al.  Nonsteroidal anti‐inflammatory drugs and risk of ovarian cancer: systematic review and meta‐analysis of observational studies , 2013, Acta obstetricia et gynecologica Scandinavica.

[38]  P. Rothwell,et al.  Effects of regular aspirin on long-term cancer incidence and metastasis: a systematic comparison of evidence from observational studies versus randomised trials. , 2012, The Lancet. Oncology.

[39]  R. Everson,et al.  Aspirin Use and Lung, Colon, and Breast Cancer Incidence in a Prospective Study , 1994, Epidemiology.

[40]  R. Langer,et al.  The association between aspirin use and the incidence of colorectal cancer in women. , 2006, American journal of epidemiology.

[41]  M. Desai,et al.  Aspirin is associated with lower melanoma risk among postmenopausal Caucasian women , 2013, Cancer.

[42]  M. Thun,et al.  A large cohort study of long-term daily use of adult-strength aspirin and cancer incidence. , 2007, Journal of the National Cancer Institute.

[43]  C. Kooperberg,et al.  Outcomes ascertainment and adjudication methods in the Women's Health Initiative. , 2003, Annals of epidemiology.

[44]  Gianni Tognoni,et al.  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 , 2012, The Lancet.