Intervention studies on cancer

This paper (and an extensive supplementary report) considers how far cancer /risk factor associations based on epidemiology have been confirmed by evid ence from 226 studies involving interventions other than smoking. Many are small, uncontrolled, of unrepresentative populations, concern cancer marker s not cancer, and may involve combinations of agents. Many agents suspected of causing cancer are untested by intervention trials. For seven of 16 age nts tested (fibre, folic acid, low-fat diet, riboflavin, zinc, vitamin Bs, and vitamin D), the evidence is clearly inadequate to confirm or deny the e pidemiology, while the evidence relating to calcium only concerns biomarker s. For other agents, the evidence relating to cancer itself is weak In stud ies where cancer is the endpoint, only three effects have been replicated: (a) selenium supplementation and decreased liver cancer incidence, (b) trea tment by the retinoid etretinate and reduced bladder tumours in susceptible individuals, and (c) beta-carotene supplementation and increased lung canc er incidence. Studies involving pre-cancerous conditions as the endpoint, w hich have a number of practical advantages, more frequently report benefits of intervention. Thus, oral pre-cancerous lesions can certainly be reduced by beta-carotene, vitamin A, and other retinoids, and possibly by vitamin E. It also seems that retinoids can reduce pre-cancerous cervix, skin and l ung lesions, that vitamin C and the NSAID sulindac can reduce colonic polyp s, and that sunscreens can reduce solar keratoses. Our findings clearly sho w that the great majority of causal relationships suggested by epidemiology have not been validated by intervention trials. This may be partly due to lack of suitable studies of adequate size or duration, or to using single d ietary compounds as agents that are by themselves not responsible for the e pidemiologically-observed associations between diet and cancer. However, th is lack of validation must cause concern in view of the markedly conflictin g evidence on beta-carotene and lung cancer between epidemiological and int ervention studies. More intervention studies are needed, but in their absen ce, caution in interpreting epidemiological findings is warranted. (C) 1999 Lippincott Williams & Wilkins.