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DNA repair synthesis in individuals with and without a family history of cancer
Authors:Pero, Ronald W.   Johnson, Desmond B.   Markowitz, Melvin   Doyle, Geraldine   Lund-Pero, Margaretha   Seidegard, Janeric   Halper, Marilyn   Miller, Daniel G.
Affiliation:1PMI-Strang Clinic, Division of Biochemical Epidemiology 55 East 34 Street, New York, NY 10016
2Department of Molecular Ecogenetics, University of Lund Box 7031, 220 07 Lund 7, Sweden
Abstract:The influence of family history on DNA repair synthesis, unscheduledDNA synthesis (UDS), was assessed in volunteers with or withouta family history of cancer. UDS, following treatment of mononuclearleukocytes with N-acetoxy-2-acetylaminofluorene, was measuredas the incorporation of [3H] into DNA in the presence of hydroxyurea.The positive family history group (n=71) had an average of 2.4first-degree relatives with cancer, defined as any major cancer,excluding skin cancer: 31 participants reported that canceroccurred in both their parents. The ‘no family history’comparison group (n=29) had no family history of cancer throughthe second degree. There was a significant reduction in UDSin cells from individuals with family history, compared to thosewith no family history (P>0.002). This relationship was notexplained by factors known to influence UDS, such as age, smokingor hypertension. We conclude that reduced UDS in mononuclearleukocytes is associated with a family history of any majorcancer, and is not confined to a history of cancer of any singleorgan site. This conclusion is further supported by the observationthat individuals (n=13) with parents who had an earlier onsetof cancer (<60 years) also had a significantly lower DNArepair synthesis than those (n=18) whose parents had later diagnosisof cancer (>60 years).
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