Aspirin in Bladder and Prostate Cancer

Professor Dalgleish stressed that there is considerable evidence that aspirin can prevent bladder cancer. This is based on epidemiological studies and on rat bladder cancer models, in which aspirin blocks the formation of cancer-inducing compounds.

aspirin has been known to inhibit bladder metastases for many years. A prospective Harvard study of 47,000 subjects showed that aspirin had no significant effect on the incidence of bladder cancer but it possibly helped prevent metastatic spread. A French study showed that other NSAIDs also do this, even more effectively than aspirin. An Ohio study of more than 400 patients showed a 66% reduction of tumour in both the aspirin and other NSAIDs groups. Oakland showed a RR of 0.76 in people taking more than 6 aspirins a day for a year. A Canadian study in 2000 showed a similar reduction. The fact that other NSAIDs may protect against bladder cancer even more effectively than aspirin, may point to a novel non-COX-2 pathway as the underlying mechanism. Phenacetin, in contrast to aspirin and NSAIDs, seems to promote bladder cancer.

The role of aspirin in prostate cancer is more controversial. Some studies suggest a clear protective role for aspirin against the development of prostate cancer: others show no statistical benefit. Some claim that aspirin may reduce metastatic (distant) spread, but will not prevent the initiation of prostate cancer. Yet other studies suggest that dose is critically important for blocking prostate cancer progression. One of the most recent studies suggests that low dose aspirin may be more effective than the larger anti-inflammatory doses, suggesting that the benefit may be because it reduces clotting within the prostate. Other studies report that anticoagulants, such as heparin are beneficial in cancer: this may be the same for aspirin. Most of the trials have suggested that anticoagulants prevent the distant spread of prostate cancer, but the need to prevent serious bleeding during such treatment has prevented their widespread use.

Cancers and chronic inflammation.
The evidence that chronic inflammation leads to cancer is strong. Patients with ulcerative colitis and intestinal polyps develop colon cancer. Schistosomiasis leads to bladder cancer. Prostatitis may lead to prostate cancer. There are similar links between bronchitis and lung cancer, oesophagitis and oesophageal cancer, gastritis and stomach cancer, and hepatitis B and C and liver cancer. Common to all of them are chronic immune alteration and inflammation.

Cell mediated (Th-1) and humoral mediated (Th-2) systems are normally in balance. Chronic inflammation leads to suppression of cell mediated immunity with down regulation of Th-1. Cancer is caused by mutation of growth and differentiation cells. A carcinogen initiates changes, which lead to promotion of tumour growth, and eventually a tumour with internal hypoxia. Angiogenesis is present early, even before the switch to carcinogenesis. The changes in relative Th-1 and Th-2 response can be reversed using a non-specific stimulation of the immune system, but prostate cancer patients have reduced immune responses.

Chronic inflammation activation is important in early tumours. aspirin should be useful at this stage. It inhibits inflammation and clotting independently and may give protection in the prostate by blocking oncogenic (cancer-promoting) signalling pathways. It inhibits angiogenesis and suppresses cell mediated immune surveillance.

Finally, Professor Dalgleish stressed that it may be wrong to reject aspirin for the 'superaspirins' that block only COX-2 because they may not work in the same way.

Professor John Burn, Clinical Director of the NHS Northern Genetics Service and Medical Director of the University of Newcastle upon Tyne Institute of Human Genetics, then described his work on preventing bowel cancer with aspirin.