title: Constitutional chromosome instability and cancer risk.
abstract: Acquired, clonal chromosome abnormalities are thought to be of pathogenetic importance in human cancer; at the cellular level, neoplasia is best viewed as a genetic disease. It is therefore logical to suggest that cancer risk must somehow be related to individual variations in genomic stability. Those persons whose chromosomes are less stable will, on average, be the ones who are most likely to develop cancer. The testing of this hypothesis shows that, apart from the autosomal recessive chromosome breakage syndromes, only patients with adenomatosis of the colon and rectum have, consistently and by different groups, been found to display elevated spontaneous and clastogen-induced chromosome breakage frequencies. Some evidence indicates a similar tendency in patients with dysplastic nevus syndrome, basal cell carcinoma, cervix cancer, and Kaposi's sarcoma. For several other cancers the data strongly argue against any inherent genomic instability. Although most results thus fail to support constitutional chromosome fragility as a factor of importance in tumorigenesis, conclusive falsification of the hypothesis cannot be said to have been obtained. The possibility remains that variations in chromosome stability and clastogen sensitivity between different cell types, and also difficulties in selecting the most appropriate carcinogens in clastogen-exposure tests, may have masked systematic constitutional differences between patients and controls in the breakage assays.
authors.affiliation: Department of Clinical Genetics, Lund University Hospital, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Heim
authors.forename: B
authors.initials: B
authors.lastname: Johansson
authors.forename: F
authors.initials: F
authors.lastname: Mertens
mesh_terms: D002869:Chromosome Aberrations; D006801:Humans; D009153:Mutagens; D009369:Neoplasms / Q000235:genetics*; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics; D012307:Risk Factors
chemical_list: D009153:Mutagens