Chronic low dose UV exposure and p53 mutation: tilting the odds in early epidermal preneoplasia?

This review addresses how mutation of the TP53 gene (p53) and ultraviolet light alter the behavior of normal progenitor cells in early epidermal preneoplasia.

Cancer is thought to evolve from single mutant cells, which expand into clones and ultimately into tumors. While the mutations in malignant lesions have been studied intensively, less is known about the earliest stages of preneoplasia, and how environmental factors may contribute to drive expansion of mutant cell clones. Here we review the evidence that ultraviolet radiation not only creates new mutations but drives the exponential growth of the numerous p53 mutant clones found in chronically exposed epidermis. Published data is reconciled with a new paradigm of epidermal homeostasis which gives insights into the behavior of mutant cells. We also consider the reasons why so few mutant cells progress into tumors and discuss the implications of these findings for cancer prevention.