Introduction Selective cyclo-oxygenase-2 (COX2) inhibitors are a widely used analgesic for patients with intolerance to traditional non-steroidal anti-inflammatory drugs and it is unclear how long-term use affects cancer risk.

Methods A series of nested case-control studies were conducted using data from 574 UK general practices in the QResearch primary care database. All patients diagnosed with cancer between 1998 and 2008 were matched with up to 5 controls. Associations of COX2 inhibitors with risk of all cancers and 10 site-specific cancers (breast, prostate, lung, colorectal, haematological, bladder, melanoma, gastric, pancreatic and oesophageal) were estimated using conditional logistic regression adjusted for co-morbidities, smoking status, socio-economic status and use of non-steroidal anti-inflammatory drugs, aspirin and statins.

Results 88 125 cases with cancer and 362 254 matched controls with at least 6 years of records were analysed. Use of COX2 inhibitors for more than a year was associated with significantly increased overall risk of cancer (OR 1.06, 95% CI 1.03 to 1.09), particularly breast cancer (OR 1.24, 95% CI 1.08 to 1.42) and haematological malignancies (OR 1.38, 95% CI 1.12 to 1.69). Risk of colorectal cancer was significantly decreased (OR 0.76, 95% CI 0.63 to 0.92) for COX2 inhibitor usage of more than a year. There were no other significant associations.

Conclusion In this large population-based case-control study, prolonged use of COX2 inhibitors was associated with increased risk of breast and haematological cancers and decreased risk of colorectal cancer. These findings need to be confirmed using other data sources.