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Title: Studies on the genetic epidemiology of heritable breast cancer
Author: Porter, Daniel Edward
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1995
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Pedigrees with two or more cases of breast cancer were collected from southeast Scotland. Data were corroborated from the Registrar General for Scotland's records. Constitutional DNA from members of 15 pedigrees, each containing between 3 and 8 cases of breast cancer, was extracted from blood lymphocytes and paraffin-embedded material. Polymorphic markers on chromosome 17 were screened to locate a putative breast cancer susceptibility gene by means of linkage analysis in these families. Pairwise Lod scores were calculated at 5 loci. The maximal summated Lod was +5.62 at hypothetical genetic distance theta = 2.5cM from marker 42D6. A genetic exclusion map of critical recombinants in five linked pedigrees suggested that the susceptibility gene (BRCA1) could be flanked by markers 42D6 and MFD188 (D17S579); a region 5 - 10 cM in length mapping to chrosome 17q12-21. In eight pedigrees a posterior probability of linkage to BRCA1 was calculated as greater than 75% (range 79.2% - 99.9%) and a total of 102 female relatives from these families were typed with one or both of adjacent markers 42D6 and MFD188. Lifetime disease penetrance of BRCA1 gene mutation was calculated to be 88%. The survival curve in probable BRCA1 mutation carriers who developed breast cancer appeared to be less steep than in the general population. Two breast cancer pedigrees were found to contain individuals in which specific p53 point mutations could be identified as important heritable susceptibility factors for breast and other tumours. These studies have enabled high-risk women from both BRCA1 and p53 gene mutation carrying families to be identified and discriminated from their low-risk, non-gene carrying relatives; an important prerequisite for improved survival in familial breast cancer.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available