Objective To examine whether anti-inflammatory drug treatment protects against the commoner cancers in the United Kingdom.

Design Case-control study using the general practice research database.

Setting Practices throughout United Kingdom providing data to the database.

Subjects Patients who had a first diagnosis of five gastrointestinal (oesophagus, stomach, colon, rectum, and pancreas) cancers and four non-gastrointestinal (bladder, breast, lung, and prostate) cancers in 1993-5 for whom prescription data were available for the at least the previous 36 months. Each case was matched for age, sex, and general practice with three controls.

Main outcome measure Risk of cancer.

Results In 12 174 cancer cases and 34 934 controls overall risk of the nine cancers was not significantly reduced among those who had received at least seven prescriptions in the 13-36 months before cancer diagnosis (odds ratio 0.98, 95% confidence interval 0.89 to 1.07). Findings were nevertheless compatible with protective effects from anti-inflammatory drugs against cancers of the oesophagus (0.64, 0.41 to 0.98), stomach (0.51, 0.33 to 0.79), colon (0.76, 0.58 to 1.00), and rectum (0.75, 0.49 to 1.14) with dose related trends. The risk of pancreatic cancer (1.49, 1.02 to 2.18) and prostatic cancer (1.33, 1.07 to 1.64) was increased among patients who had received at least seven prescriptions, but the trend was dose related for only pancreatic cancer.

Conclusions Anti-inflammatory drugs may protect against oesophageal and gastric cancer as well as colon and rectal cancer. The increased risks of pancreatic and prostatic cancer could be due to chance or to undetected biases and warrant further investigation.

Introduction

Epidemiological evidence has consistently shown that people who have taken aspirin or other non-steroidal anti-inflammatory drugs are at reduced risk of developing or dying from colon cancer.[1 2] The extent to which treatment protects against other cancers is unclear, although in epidemiological studies fewer fatal cases of gastric and oesophageal cancer than expected have been found[2] and the occurrence of experimentally induced bladder, breast, and colon cancer in animals has been reduced by giving non-steroidal anti-inflammatory drugs concurrently with carcinogens.[3-5]

The extent to which treatment might protect against different varieties of cancer in humans could be investigated by separate case-control or case-cohort studies, but this time consuming and labour intensive method can be avoided by examining information held on automated databases that record drug prescriptions and clinical outcomes. We used the general practice research database to examine information about previous prescription of aspirin and other nonsteroidal anti-inflammatory drugs and occurrence of the common cancers in the United Kingdom.

Methods

The general practice research database is a national dataset managed for the Department of Health containing anonymised patient records on about four million UK residents. Contributing general practices, which are distributed throughout the United Kingdom, record standard data on demography, morbidity, and prescriptions and selected other information. The quality of data is regularly assessed.[6] With ethics committee approval we identified practices with at least four years of information meeting the required standard and abstracted data on all patients with a first diagnosis of five gastrointestinal cancers (oesophagus, stomach, pancreas, colon, and rectum) and four non-gastrointestinal cancers (bladder, breast, lung, and prostate) during 1993-5. Each case was then individually matched for age (within five years), sex, and general practice with three controls. Controls were patients without a diagnosis of the case’s type of cancer at the time the case was diagnosed. We also obtained information on recorded current smoking habits.

Data on prescriptions for aspirin and other non-steroidal anti-inflammatory drugs (all drugs listed in British National Formulary subsection 10.1.1) were extracted for each case and control for the 13-36 months before cancer diagnosis (and equivalent data were extracted for controls). Information on smoking habits was used to classify patients as ever smokers or never smokers. Conditional logistic regression was used to analyse associations between numbers of prescriptions and risk of cancer for all sites together and each separately. Odds ratios (adjusted for smoking habits and age) were calculated with 95% confidence intervals, and dose-response relations were tested for trend. In the primary analyses we examined overall cancer incidence in relation to drug use and compared risks of gastrointestinal and non-gastrointestinal cancers.

Results

We identified 12 174 patients with a first diagnosis of the study cancers in 1993-5 who had prescription data available for the previous 36 months. Eighteen patients with multiple cancers were excluded from analyses of individual sites, with their controls. Table 1 shows, for each cancer site, the numbers of cases and matched controls by sex and the numbers who had ever received prescriptions for aspirin or other nonsteroidal anti-inflammatory drugs.