Genetic Instability and Tumorigenesis

Volume 221 of the series Current Topics in Microbiology and Immunology pp 47-70

Role of DNA Excision Repair Gene Defects in the Etiology of Cancer

  • J. M. FordAffiliated withDepartment of Biological Sciences, Stanford University
  • , P. C. HanawaltAffiliated withDepartment of Biological Sciences, Stanford University

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Experimental and clinical evidence strongly suggests that exposure to environmental carcinogens is a critical event in the development of the majority of human cancers. Mutations in genes important for normal cellular functions and growth properties, including many proto-oncogenes and tumor suppressor genes, may result from spontaneous or environmentally induced alterations in DNA and contribute directly to the multistage process leading to malignancy. In addition, alterations in the specific genes required for processing and responding to DNA damage may result in an enhanced rate of accumulation of additional mutations, recombinational events, chromosomal abnormalities, and gene amplification (Loeb 1991). Therefore, the removal of lesions from DNA is essential not only for the basic processes of transcription and replication necessary for cellular survival, but also for maintaining genomic stability and avoiding the development of malignancies.