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Tamar Lasky and Laurence Magder

Department of Epidemiology and Preventive Medicine, School of Medicine, University of Maryland at Baltimore, Baltimore, MD 21201-1596 USA

Abstract
The molecular epidemiology of p53 mutations allows the possibility of correlating particular mutations with specific environmental carcinogens 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 their agricultural products. In this paper, we describe a systematic review of the literature and assess the quality of the available data. We found methodologic limitations in the studies. In particular, the key independent variable, aflatoxin exposure, was not assessed in these studies, with the exception of one study that measured a marker of exposure. Instead, nationality, geographic residence, or geographic site of hospital were used as surrogate markers for exposure. Patients from areas 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 high aflatoxin levels had higher proportions of mutations with codon 249 G>T transversions. The differences in proportions with p53 mutations were significant, as were 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 transversion, thus explaining some of the excess liver cancer associated with aflatoxin exposure. However, it is premature to conclude that p53 mutations are established markers for environmental carcinogens. Key words: cancer, epidemiology, gene, hepatocellular carcinoma, meta-analysis, molecular epidemiology, mutation, p53. Environ Health Perspect 105:392-397 (1997)

Address correspondence to T. Lasky, Department of Epidemiology and Preventive Medicine, School of Medicine, University of Maryland at Baltimore, Gray Lab, Room 209, 520 West Lombard Street, Baltimore, MD 21201-1596 USA.

The analysis was supported by a grant from the Heinz Family Foundation. The authors thank Carol Rice and Ellen Silbergeld for their comments. Received 22 October 1996 ; accepted 8 January 1997.