PT  - JOURNAL ARTICLE
AU  - Jervis, Sarah
AU  - Song, Honglin
AU  - Lee, Andrew
AU  - Dicks, Ed
AU  - Harrington, Patricia
AU  - Baynes, Caroline
AU  - Manchanda, Ranjit
AU  - Easton, Douglas F
AU  - Jacobs, Ian
AU  - Pharoah, Paul P D
AU  - Antoniou, Antonis C
TI  - A risk prediction algorithm for ovarian cancer incorporating <em>BRCA1, BRCA2</em>, common alleles and other familial effects
AID  - 10.1136/jmedgenet-2015-103077
DP  - 2015 Jul 01
TA  - Journal of Medical Genetics
PG  - 465--475
VI  - 52
IP  - 7
4099  - http://jmg.bmj.com/content/52/7/465.short
4100  - http://jmg.bmj.com/content/52/7/465.full
SO  - J Med Genet2015 Jul 01; 52
AB  - Background Although BRCA1 and BRCA2 mutations account for only ∼27% of the familial aggregation of ovarian cancer (OvC), no OvC risk prediction model currently exists that considers the effects of BRCA1, BRCA2 and other familial factors. Therefore, a currently unresolved problem in clinical genetics is how to counsel women with family history of OvC but no identifiable BRCA1/2 mutations.Methods We used data from 1548 patients with OvC and their relatives from a population-based study, with known BRCA1/2 mutation status, to investigate OvC genetic susceptibility models, using segregation analysis methods.Results The most parsimonious model included the effects of BRCA1/2 mutations, and the residual familial aggregation was accounted for by a polygenic component (SD 1.43, 95% CI 1.10 to 1.86), reflecting the multiplicative effects of a large number of genes with small contributions to the familial risk. We estimated that 1 in 630 individuals carries a BRCA1 mutation and 1 in 195 carries a BRCA2 mutation. We extended this model to incorporate the explicit effects of 17 common alleles that are associated with OvC risk. Based on our models, assuming all of the susceptibility genes could be identified we estimate that the half of the female population at highest genetic risk will account for 92% of all OvCs.Conclusions The resulting model can be used to obtain the risk of developing OvC on the basis of BRCA1/2, explicit family history and common alleles. This is the first model that accounts for all OvC familial aggregation and would be useful in the OvC genetic counselling process.