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Genetic predisposition to cancer.

A G Knudson

    Cancer Detection and Prevention
    |January 1, 1984
    PubMed
    Summary

    A small percentage of cancers stem from inherited genetic mutations. A two-step genetic model, involving two mutations, may explain a large portion of human cancers, both hereditary and nonhereditary.

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    Area of Science:

    • Oncology
    • Genetics
    • Cancer Biology

    Background:

    • A minority of cancers arise from inherited genetic predispositions.
    • Retinoblastoma and Wilms' tumor are key examples of dominantly transmissible genetic predispositions to cancer.

    Purpose of the Study:

    • To propose a general genetic model for human cancer initiation.
    • To explain the role of mutations in both hereditary and nonhereditary cancer development.

    Main Methods:

    • Analysis of genetic mutations in hereditary and nonhereditary cancer cases.
    • Comparison of mutation sites in tumor cells and germline DNA.
    • Development of a two-event genetic model for cancer.

    Main Results:

    • Hereditary cancers involve mutations at specific chromosomal sites, sometimes visible as deletions.
    • Nonhereditary cancers frequently show deletions at the same sites in tumor cells, indicating a necessary initiating mutation.
    • A two-event genetic model, involving an initial mutation and a subsequent recessive event, explains cancer incidence.

    Conclusions:

    • A specific gene mutation is likely necessary for initiating most human cancers, regardless of inheritance.
    • A two-event genetic model involving recessive loss of a gene is proposed for a significant fraction of human cancers.
    • This model aligns with observed age-specific cancer incidence rates.

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