Genetic and environmental factors in the etiology of human brain tumors

Experimental studies in rodents using chemical carcinogens and viral oncogenes show a high susceptibility to malignant transformation. Analytical epidemiological studies have revealed an increased risk of human brain tumor development in association with certain occupations but, with the exception of therapeutic X-irradiation, attempts to identify a specific exposure or causative environmental agent have so far been unsuccessful. Thus, endogenous mutations and genetic factors may play a more important role. This view is supported by recent studies on the nature of DNA alterations in human brain tumors. More than 70% of p53 mutations observed during glioma progression are G:C --> A:T transitions, predominantly at CpG sites, i.e. likely to be produced by deamination of 5-meC or related spontaneous mechanisms. No specific mutations or mutational hot spots were found which could be suggestive of environmental carcinogens operative in the etiology of human brain tumors. A similar pattern of mutation is found in colon cancer, sarcomas, and lymphomas, i.e. neoplasms with largely unknown etiology. This is similarly true for p53 germline mutations which again show a strong preference for G:C --> A:T transitions at CpG sites.