A probability model for predicting BRCA1 and BRCA2 mutations in breast and breast-ovarian cancer families.

Germline mutations in BRCA1 and BRCA2 genes predispose to hereditary breast and ovarian cancer. Our aim was to find associations between the clinical characteristics and positive mutation status in 148 breast cancer families in order to predict the probability of finding a BRCA mutation in a family. Several factors were associated with mutations in univariate analysis, whereas in multivariate analysis (logistic regression with backward selection) only the age of the youngest breast cancer patient and the number of ovarian cancer cases in a family were independent predictors of BRCA mutations. A logistic model was devised to estimate the probability for a family of harbouring a mutation in either BRCA1 or BRCA2. Altogether, 63 out of 148 families (43%) and 28 out of 29 (97%) mutation carrier families obtained probabilities over 10%. The mean probability was 55% for mutation-positive families and 11% for mutation-negative families. The models by Couch et al (1997) and Shattuck-Eidens et al (1997) previously designed for BRCA1 were also tested for their applicability to distinguish carrier families with mutations in either gene. The probability model should be a useful tool in genetic counselling and focusing the mutation analyses, and thus increasing also the cost-effectiveness of the genetic screening.

Vahteristo P ，Eerola H ，Tamminen A ，Blomqvist C ，Nevanlinna H ... -  《-》

A high occurrence of BRCA1 and BRCA2 mutations among Czech hereditary breast and breast-ovarian cancer families.

Machácková E ，Foretová L ，Navrátilová M ，Valík D ，Claes K ，Messiaen L ... -  《-》

Characteristics of small breast and/or ovarian cancer families with germline mutations in BRCA1 and BRCA2.

Ligtenberg MJ ，Hogervorst FB ，Willems HW ，Arts PJ ，Brink G ，Hageman S ，Bosgoed EA ，Van der Looij E ，Rookus MA ，Devilee P ，Vos EM ，Wigbout G ，Struycken PM ，Menko FH ，Rutgers EJ ，Hoefsloot EH ，Mariman EC ，Brunner HG ，Van 't Veer LJ ... -  《-》

Application of BRCA1 and BRCA2 mutation carrier prediction models in breast and/or ovarian cancer families of French Canadian descent.

Oros KK ，Ghadirian P ，Maugard CM ，Perret C ，Paredes Y ，Mes-Masson AM ，Foulkes WD ，Provencher D ，Tonin PN ... -  《CLINICAL GENETICS》

Frequency of BRCA1 and BRCA2 mutations in a clinic-based series of breast and ovarian cancer families.

Mutations in BRCA1 and BRCA2 account for a significant proportion of hereditary breast and ovarian cancer cases. In this study, we sought to determine the frequency of BRCA1- and BRCA2-mutation carrier families in a hospital-based cancer family registry. The frequency of families with germline truncating mutations in BRCA1 and BRCA2 was 17.3% (18/104) and 1.9% (2/104), respectively. Two novel truncating mutations, BRCA1 1848delGA and BRCA2 5694insT, were identified. We also sought to determine the carrier frequency of other affected family members for which the mutation lineage could be established within these families. Not including the probands, 72% (18/25) of the affected family members within the BRCA1 mutation-associated families were carriers, and all four affected members of the BRCA2 families were carriers. These data imply that risk evaluation based on cancer family history alone may result in inaccurate estimates, and where possible, mutation testing should be considered in other affected family members to verify carrier status.

Vaziri SA ，Krumroy LM ，Rostai M ，Casey G ... -  《-》