Mutation selection and the natural history of cancer

  title={Mutation selection and the natural history of cancer},
  author={John Jr. Cairns},
Survival of the rapidly renewing tissues of long-lived animals like man requires that they be protected against the natural selection of fitter variant cells (that is the spontaneous appearance of cancer). This article discusses three possible protective mechanisms and shows how they could explain various features of the natural history of certain common cancers of man. 

The mutation rate and cancer.

It is shown that selection is more important than an increased mutation rate in the growth of a tumor, and some cancers may acquire a "mutator phenotype" leading to faster growth, but mutator phenotypes are not necessary for carcinogenesis.

Mutation and cancer: the antecedents to our studies of adaptive mutation.

> It is clear that the experimental evidence supporting many currently popular hypotheses concerning mutational processes is quite inadequate. > > ([Drake 1970][1]) LITTLE excuse is needed for

Lineage selection and the evolution of multistage carcinogenesis

  • L. Nunney
  • Biology
    Proceedings of the Royal Society of London. Series B: Biological Sciences
  • 1999
The ‘two–hit’ model so successfully applied to retinoblastoma is unlikely to be generally applicable to other human cancers; instead, more complex scenarios are expected to dominate, with complexity depending upon a tissue's size and its pattern of proliferation.

Somatic Mutation: Early Cancer Steps Depend on Tissue Architecture

Cancer selection

New theory predicts that cancer selection — selection to prevent or postpone deaths due to cancer — should be especially important as animals evolve new morphologies or larger, longer-lived bodies, and might account for some of the differences in the causes of cancer between mice and men.

Origin of mutation in neoplasia.

Clonal evolution in cancer

The inherently Darwinian character of cancer is the primary reason for this therapeutic failure, but it may also hold the key to more effective control.

Molecular tumor clocks to study the evolution of drug resistance.

How the evolution of individual human cancers may be inferred by comparing genomic variation from different parts of the same tumor is outlined.

Causality and Chance in the Development of Cancer.

In addition to heredity and the environment, chance may also play a role in the development of cancer. Because the acquisition of mutations is stochastic with each cell division, organs with more



Multiple-Mutation Theory of Carcinogenesis

A law of the same form, (age)p−1, is deduced for the rate of appearance of cancers in a population, with p now being the number of mutations required in a single cell.

A Two-stage Theory of Carcinogenesis in Relation to the Age Distribution of Human Cancer

Several of the other principal epidemiological characteristics of human cancer could also be accounted for if carcinogenesis were a complex process of six or seven stages and the degree of exposure to the factors inducing the changes from one stage to another varied, either with age or from one year to another.

A direct measurement of the radiation sensitivity of normal mouse bone marrow cells.

Counts of macroscopic splenic colonies were used to obtain an estimate of the radiation sensitivity of normal mouse bone marrow progenitor cells. Reproduced from Radiation Research 1961(Feb); 14(2):


Rabbit epidermis is much more responsive to carcinogenic influences than that of the mouse, as measured in terms of time taken to elicit benign neoplasms.

The Age Distribution of Cancer: Implications for Models of Carcinogenesis

Ten years ago in the introduction to a paper on "Stochastic Models for Carcinogenesis" Armitage and Doll noted that a variety of models had been put forward, none of which had gained general acceptance, and it seemed reasonable to maintain an interest in the topic.

Cryptogenic cells and proliferative cells in intestinal epithelium.

  • J. HendryC. Potten
  • Biology
    International journal of radiation biology and related studies in physics, chemistry, and medicine
  • 1974
SummaryThe number of cells in the mouse intestinal crypt that are capable of crypt regeneration after radiation damage was estimated to be 44+20−14, which is less than the known number of about 135

Segregation of Sister Chromatids in Mammalian Cells

Segregation of sister chromatids in embryonic mouse cells in primary tissue culture and in cells of the Chinese hamster follows a similar, but less pronounced, pattern.

Etiology of human breast cancer: a review.

The hypothesis that breast cancer risk is related to estrogen metabolism during the first few years after menarche is the hypothesis most compatible with all the major epidemiological features of the disease and is virtually the only acceptable explanation.

Genetic variants of glucose‐6‐phosphate dehydrogenase in the study of carcinoma of the cervix

Sequential studies of one patient with invasive carcinoma suggest the utility of G‐6‐PD electrophoresis for determining effectiveness and progress of treatment and raise the possibility of a heterogeneous etiology of invasive cervical epidermoid carcinoma.