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An evolutionary perspective on field cancerization

Key Points

  • Mutations naturally accrue and clonally expand in ageing tissues, but only a subset of these mutations increases the risk of cancer development.

  • A cancerized lineage is one that has acquired some but not all the phenotypic traits required for malignancy. Typically, this means that a cancerized lineage has a survival or growth advantage over normal cells but is incapable of growing into a tumour.

  • Field cancerization is both enabled by and causes changes to the tissue microenvironment.

  • Mutagen exposure and naturally occurring age-related mutations initiate cancerized fields.

  • Field cancerization can occur without morphological change, meaning that histopathology of a tissue alone is an inadequate biomarker of cancer risk.

  • Measurements of the evolution of the cancerized field offer promise as a new class of biomarker of cancer risk and provide a means to mechanistically assess the impact of chemoprevention strategies.

  • Longitudinally collected tissue samples from patients undergoing surveillance in tissues frequently affected by field cancerization provide an underexploited resource for the study of clonal evolution over space and time in humans.


Tumorigenesis begins long before the growth of a clinically detectable lesion and, indeed, even before any of the usual morphological correlates of pre-malignancy are recognizable. Field cancerization, which is the replacement of the normal cell population by a cancer-primed cell population that may show no morphological change, is now recognized to underlie the development of many types of cancer, including the common carcinomas of the lung, colon, skin, prostate and bladder. Field cancerization is the consequence of the evolution of somatic cells in the body that results in cells that carry some but not all phenotypes required for malignancy. Here, we review the evidence of field cancerization across organs and examine the biological mechanisms that drive the evolutionary process that results in field creation. We discuss the clinical implications, principally, how measurements of the cancerized field could improve cancer risk prediction in patients with pre-malignant disease.

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Figure 1: Characterization and initiation of a cancerized field.
Figure 2: Evolutionary trajectories of cancerized clones.
Figure 3: Morphological mechanisms and examples of clonal expansion.


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The authors thank D. Brash for helpful conversations during the writing of this manuscript. The authors acknowledge funding from Cancer Research UK (grants A19771 to T.A.G. and A21870 to N.A.W.), the Wellcome Trust (202778/Z/16/Z to T.A.G.) and the Barts Charity (472–2300 to K.C. and T.A.G.).

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All authors researched data for the article, made substantial contributions to discussion of the content, wrote the article and reviewed and edited the manuscript before submission.

Corresponding author

Correspondence to Trevor A. Graham.

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Cell lineage

A group of cells that share a recent common ancestor cell; also known as a clone.


Gains or losses of DNA methylation or heritable chromatin changes; such changes are in contrast to genetic changes to DNA nucleotides.

Cancerized field

A collection of cells that have gained some but not all the phenotypic alterations required for malignancy; in general, the altered phenotype will have been caused by an underlying mutation.


A feature of tissues in which cells have an abnormal morphology or arrangement, usually regarded as being an unequivocal neoplastic alteration.


A feature of tissues in which an increase in cell number occurs without malignant change.


A feature of tissues in which the usual cells of a tissue are replaced with a cell type that morphologically resembles another tissue type.

Inflammatory bowel disease

(IBD). A group of inflammatory conditions of the bowel that includes ulcerative colitis and Crohn's disease.

Sporadic tumour

A tumour that does not share tumorigenic mutations and/or other neoplastic changes in phenotype with the surrounding tissue.

Genetically mosaic

A feature of a group of cells that is composed of two or more clonal populations, each with a different genotype.

Driver mutations

Mutations that are positively selected for and are implicated in tumorigenesis.


The interaction of multiple genes that leads to the development of a phenotypic trait.


An attribute of a lesion that is derived from two or more clones as opposed to a monoclonal origin.

Metachronous tumours

Primary tumours arising sequentially in time.

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Curtius, K., Wright, N. & Graham, T. An evolutionary perspective on field cancerization. Nat Rev Cancer 18, 19–32 (2018).

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