Despite the recent cloning of BRCA1, BRCA2 and the mismatch repair
it will still be a long
time before it is possible to specify any individual's risk for
ovarian cancer based on her genotype.
Most women concerned about their risk on the basis of one or two
affected relatives do not belong
to extensive ovarian cancer families. Risk calculations depend on a
reliable genetic model for ovarian
cancer derived, ideally, from the population from which an individual
is drawn. We have carried out
a segregation analysis using data collected from consecutive ovarian
cancer patients in two different
centres in the UK. Complex segregation analysis was carried out with
the addition of diathesis as a
separate parameter allowing other cancers, associated with ovarian
cancer, to be taken into account.
The use of diathesis in the derivation of this alternative model is
described. Analysed under joint
likelihood without diathesis, the gene frequency is 0·0028 and
penetrance to age 70 years is 50%. This
is in agreement with other published models. Incorporating diathesis
into the model under joint
likelihood gives similar parameters for a single locus model but gives
the best fit with a two locus model where both genes are rare.