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Exposure to cyclo-oxygenase-2 inhibitors and risk of cancer: nested case-control studies . Yana Vinogradova , Carol Coupland, Julia Hippisley-Cox. IAE world Congress Epidemiology 2011 Edinburgh. Background. COX2i used for patients intolerant to NSAIDs
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Exposure to cyclo-oxygenase-2 inhibitors and risk of cancer:nested case-control studies Yana Vinogradova, Carol Coupland, Julia Hippisley-Cox IAE world Congress Epidemiology 2011 Edinburgh
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
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
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
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
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
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
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)
Methods: Statistical analysis Multiple imputations Conditional logistic regression Odds ratios + 95% CI 1% significance level
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
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
Limitations Information on prescriptions only Residual confounding Missing data
Acknowledgements EMIS
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