1. Exposure to cyclo-oxygenase-2 inhibitors and risk of cancer: nested case-control studies IAE world Congress Epidemiology 2011 Edinburgh Yana Vinogradova, Carol Coupland, Julia Hippisley-Cox

2. Background COX2i used for patients intolerant to NSAIDs Lab investigations suggested mechanism for reducing risk of cancer Epidemiological studies –Colorectal, RCT 36% decreased risk –Breast, lung - small studies – decreased risk –THIN (general population) no difference

3. Aim of the study To determine association between selective COX2i and risk of common cancers: –Breast– Prostate –Colorectal– Lung –Blood– Melanoma –Gastric – Bladder –Pancreas– Oesophageal

4. Methods: Source of data QResearch Currently largest database in the UK 602 UK practices > 6 practices in every Strategic Health Authority (administrative area) > 12 million patients including those who died, left and still registered

5. Source of data: QResearch Patient level consolidated database Anonymised data Longitudinal data for 15+ years Derived from GP clinical records Validated against external and internal measures Industry independent

6. Methods: Study design Nested case control study 574 UK general practices Study period Jan 1998-July 2008 aged between 30 and 100 years Up to 5 controls matched by –Age –Sex –Practice –Calendar year

7. Methods: Assessment of Exposure at least 6 years of prescribing data excluding 1 year before the index date use: at least 1 script in prior 13 to 72 months cumulative use: <3m, 3-12m, 13-24m, 25-60m Short-term (<12m), long-term users median dose: low/medium, high different types of COX2i

8. Methods: Confounding factors Socio-economic status (Townsend score) Body mass index Smoking status Morbidities (CVD, HBP, DM, RA, osteoarthritis) Additional confounders (Benign breast disease, family history; Colitis, Crohn’s disease) Other medications (NSAIDs, Aspirin, statins, contraceptive pills, HRT)

9. Methods: Statistical analysis Multiple imputations Conditional logistic regression –Odds ratios + 95% CI –1% significance level

10. Results: Sample 118,780 incident cases of cancer 1998/2008 113,879 cases with primary cancer 88,125 cases with 6 years of medical records 6,901 COX2i users

16. Summary of findings Long-term use of COX2i : 24% reduced risk of colorectal cancer 24% increased risk of breast cancer 38% increased risk of blood cancer

17. Strengths Large sample size and representative population Data electronically collected – unlikely misclassification bias Data collected before the diagnosis – no recall bias Data in the last 12 months before the diagnosis was excluded as might be misleading

18. Limitations Information on prescriptions only Residual confounding Missing data

19. Acknowledgements EMIS

20. Thank you Questions? Y Vinogradova, C Coupland, J Hippisley-Cox “ Exposure to cyclo- oxigenase-2 inhibitors and risk of cancer: nested case-control study” 2011, British Journal of Cancer, 105(3), 452-459