P. Margarittejeannin et al., GENETIC-COUNSELING IN BREAST-CANCER - SENSITIVITY TO PARAMETER VALUESAND TO AVAILABLE INFORMATION, Annales de genetique, 38(1), 1995, pp. 19-25
Most segregation analyses have concluded that breast cancer results fr
om a mixture of sporadic and genetic cases. Genetic cases are probably
due to a rare inherited mutation with autosomal dominant transmission
. The lifetime risk for female mutation carriers is close to 1, ten fo
ld greater than for noncarriers. Beyond these accepted results, studie
s differ in the estimated parameters specifying the correspondence bet
ween phenotypes and genotypes. We show here that these differences hav
e an impact on the estimation of the probability that a woman is carry
ing a mutation given her disease status and also given the information
on the disease status of her family members. We illustrate this probl
em by computing the probability of being a mutation earner for 16 wome
n (9 affected, 7 unaffected) belonging to one pedigree, using three se
ts of parameter values. For two of the women, the probability that the
y inherited the mutation is low, but it vanes considerably according t
o the set of parameter values. For one woman, the probability varies f
rom 20 to 60 % if familial information is taken into account. Segregat
ion of 17q markers in families may provide additional information depe
nding on the posterior probability of linkage. Indeed, in the pedigree
studied here, the segregation of 17q markers provided additionnal inf
ormation which moreover decreased the sensitivity to the parameters va
lues. However, the decrease in sensitivity will only be observed if th
e posterior probability df linkage of the family to the studied marker
s is high.