P L Friedlander1. 1. Department of Otolaryngology and Biocommunication, Louisiana State University Health Sciences Center, 533 Bolivar Street, 5th Floor, New Orleans, Louisiana 70112, USA. pfried@lsuhsc.edu
Abstract
BACKGROUND: In the normal host, there are a variety of cellular systems that ensure the accurate replication and repair of DNA. Recent evidence suggests that there are individual variations in the ability to preserve the genome. Certain individuals have defects in these checkpoints and have an inherent genomic instability. They are susceptible to the accumulation of DNA damage and are prone to carcinogenesis. This article examines the role of genomic instability in the development of head and neck cancer. RESULTS: Patients with either the chromosomal instability syndromes or the Li-Fraumeni syndrome have marked defects in either DNA repair or apoptosis. These patients are prone to have head and neck neoplasms develop. Head and neck cancer patients also have a diminished ability to repair DNA damage compared with the "normal" population. Abnormalities have been identified in mutagen sensitivity, the expression of DNA mismatch repair enzymes, the expression of p53, and telomerase activity when head and neck cancer patients are compared with controls. CONCLUSION: Subpopulations exist who have increased genomic instability. These individuals are at an increased risk for the accumulation of DNA mutations and the development of head and neck cancer. More research is needed to identify specific mechanisms of genomic instability and to further define the importance of this phenomenon.
BACKGROUND: In the normal host, there are a variety of cellular systems that ensure the accurate replication and repair of DNA. Recent evidence suggests that there are individual variations in the ability to preserve the genome. Certain individuals have defects in these checkpoints and have an inherent genomic instability. They are susceptible to the accumulation of DNA damage and are prone to carcinogenesis. This article examines the role of genomic instability in the development of head and neck cancer. RESULTS:Patients with either the chromosomal instability syndromes or the Li-Fraumeni syndrome have marked defects in either DNA repair or apoptosis. These patients are prone to have head and neck neoplasms develop. Head and neck cancerpatients also have a diminished ability to repair DNA damage compared with the "normal" population. Abnormalities have been identified in mutagen sensitivity, the expression of DNA mismatch repair enzymes, the expression of p53, and telomerase activity when head and neck cancerpatients are compared with controls. CONCLUSION: Subpopulations exist who have increased genomic instability. These individuals are at an increased risk for the accumulation of DNA mutations and the development of head and neck cancer. More research is needed to identify specific mechanisms of genomic instability and to further define the importance of this phenomenon.
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