A new scoring system in cancer genetics: application to criteria for BRCA1 and BRCA2 mutation screening.

Background: In hereditary forms of cancer due to mutations of genes such as BRCA1 and BRCA2, methods have been proposed to predict the presence of a mutation in a family.

Methods: Relying on carriage probability computation is the most predictive, but scores are a good proxy and avoid using computer software. An empirical method, the Manchester scoring system, has been elaborated for BRCA1 and BRCA2 mutation identification.

[A new scoring system for the diagnosis of BRCA1/2 associated breast-ovarian cancer predisposition].

Criteria have been proposed for genetic testing of breast and ovarian cancer susceptibility genes BRCA1 and BRCA2. Using simulations, this study evaluates the efficiency (sensitivity, positive predictive value [PPV] and specificity) of the various criteria used in France. The efficiency of the criteria published in 1998, which are largely used, is not optimal.

Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome.

Context: Providing accurate estimates of cancer risks is a major challenge in the clinical management of Lynch syndrome.

Objective: To estimate the age-specific cumulative risks of developing various tumors using a large series of families with mutations of the MLH1, MSH2, and MSH6 genes.

Design, Setting, And Participants: Families with Lynch syndrome enrolled between January 1, 2006, and December 31, 2009, from 40 French cancer genetics clinics participating in the ERISCAM (Estimation des Risques de Cancer chez les porteurs de mutation des gènes MMR) study; 537 families with segregating mutated genes (248 with MLH1; 256 with MSH2; and 33 with MSH6) were analyzed.

Estimating penetrance from multiple case families with predisposing mutations: extension of the 'genotype-restricted likelihood' (GRL) method.

Some diseases are due to germline mutations in predisposing genes, such as cancer family syndromes. Precise estimation of the age-specific cumulative risk (penetrance) for mutation carriers is essential for defining prevention strategies. The genotype-restricted likelihood (GRL) method is aimed at estimating penetrance from multiple case families with such a mutation.

TTR familial amyloid polyneuropathy: does a mitochondrial polymorphism entirely explain the parent-of-origin difference in penetrance?

The Val30Met transthyretin familial amyloid polyneuropathy (TTR-V30M-FAP) is the most frequent familial amyloidosis, with autosomal dominant transmission. This severe disease shows important differences in age of onset and penetrance. Recently, a difference in penetrance according to the gender of the transmitting parent was elicited in different geographic areas with a higher penetrance in case of maternal transmission of the trait.