Genetic instability in the human population: A working hypothesis1,2

Abstract

In several rare syndromes, genetic instability, expressed as chromosome instability, is known. Patients with these syndromes are predisposed to cancer. Evidence has been accumulating to show that chromosome instability occurs in some other diseases also, though the frequency was not as high. Genetic instability may induce mutational events in a chromosome (second step) whose homolog has a congenital defect (primary step) towards neoplasia in a target cell. Genetic instability may also induce the initial step. It is highly probable that genetic instability in the human population is not an all-or-none situation. Gradations of genetic instability may exist with a variety of underlying causes. Persons may have latent instability which normally cannot be detected by cytogenetic methods, e.g. defective DNA repair mechanisms. With DNA damage, there will be little or no repair in the cells of persons with defective repair systems, hence more chromosomal aberrations. When challenged with clastogens, the cells of persons with mildly defective repair systems may show a higher rate of chromosome aberrations than those of stable persons. This paper presents a working hypothesis on genetic instability in the human population and methods to detect the masked instability.