Epidemiological evidence for the role of nitroso compounds in human cancer

Human exposure to N-nitroso compounds (NOC) is not to single compounds but to highly complex mixtures such as food or tobacco products which may contain various NOC, NOC precursors and modulators of NOC metabolism in addition to other known carcinogens. Aetiological models also stress the importance of other cofactors. The interrelationship of these cofactors with relevant NOC exposures and the possible influence of confounding factors need to be considered in order to evaluate the risk related to NOC. This task is made more difficult because the levels of human NOC exposure are often low, and some of the relevant exposure is likely to be from endogenously formed NOC. Nonetheless, current hypotheses reviewed here propose a role for NOC in the aetiology of tobacco-related cancers and of cancers of the bladder, stomach, oesophagus and brain. Data implicating tobacco-specific nitrosamines in the aetiology of cancers of the oral cavity among snuff dippers is most convincing. Evidence from epidemiological studies in support of other NOC/cancer hypotheses is circumstantial and much work remains to be done to define the role of NOC and develop strategies for prevention of these tumours.