HEPATOCELLULAR-CARCINOMA P53 G-GREATER-THAN-T TRANSVERSIONS AT CODON-249 - THE FINGERPRINT OF AFLATOXIN EXPOSURE

The molecular epidemiology of p53 mutations allows the possibility of correlating particular mutations with specific environmental carcinoge ns and establishing one step in the causal pathway between exposure to carcinogens and the development of cancer. A striking example is the G>T transversion at the third base pair of codon 249 observed in liver cancer patients possibly exposed to high levels of aflatoxins in thei r agricultural products. In this paper, we describe a systematic revie w of the literature and assess the quality of the available data. We f ound methodologic limitations in the studies. In particular, the key i ndependent variable, aflatoxin exposure, was not assessed in these stu dies, with the exception of one study that measured a marker of exposu re. Instead, nationality, geographic residence, or geographic site of hospital were used as surrogate markers for exposure. Patients from ar eas with high aflatoxin levels were more likely to have p53 mutations than were patients from areas with low aflatoxin levels. In the group with p53 mutations, patients from areas with hgh aflatoxin levels had higher proportions of mutations with codon 249 G>T transversions. The differences in proportions with p53 mutations were significant, as wer e the differences in proportions of codon 249 G>T transversions among patients with p53 mutations. Aflatoxin may increase the proportion of p53 mutations by causing a single mutation, the codon 249 G>T transver sion, thus explaining some of the excess liver cancer associated with aflatoxin exposure. However, it is premature to conclude that p53 muta tions are established markers for environmental carcinogens.