Abstract 5047: Impact of parental origin of BRCA1/ 2 mutation on age at breast and ovarian cancer diagnosis
Authors: Ellberg Carolina , Jernstrom Helena , Broberg Per , Borg Ake , Olsson Hakan 
Published: May 2015

Abstract
Parental origin of the mutation may be associated with the age of breast cancer (BC) onset in BRCA1 mutation carriers, three studies have reported that paternal origin of mutation confers an earlier BC diagnosis compared to a maternal origin. The primary aim of the study was to investigate the effect of parental origin of the BRCA1/2 mutation on age at BC and ovarian cancer (OvC) diagnosis.
Material and methods:
The present study consist of 400 women with a BRCA1 mutation; 92 with paternal and 241 with maternal origin of mutation, and 177 women with BRCA2 mutation; 50 with paternal and 102 with maternal origin of mutation. All carriers belongs to families registered in the OnkGen register at the Oncogenetic Clinic at Skånes University Hospital, Lund, Sweden between 1993 and 2011. All multivariate Cox Proportional Hazard models were adjusted for year of inclusion into the OnkGen register, and year of birth. All p-values were two sided and p-values less than 0.05 were regarded statistically significant.
Results:
The median age at diagnosis for BRCA1 mutation carriers was; BC 40 and OvC 54 years for paternal origin, and BC 42 and OvC 54 years for maternal origin. For BRCA2 mutation carriers it was; BC 41 and OvC 57 years for paternal origin, and BC 47 and OvC 54 years for maternal origin. BRCA1 mutation carriers with a paternal origin of the mutation were diagnosed with breast cancer at an earlier age compared with maternal origin of mutation, HR 1.53 (95% CI 1.08-2.17) adjusted for year of inclusion and birth date. On the other hand, BRCA1 mutation carriers with a paternal origin of the mutation were older at age of ovarian cancer diagnosis compared with maternal origin of the mutation, HR 0.44 (95% CI 0.23-0.81) adjusted for year of inclusion and birth date.
Conclusions:
We have confirmed earlier reported findings that BRCA1 mutation carriers with a paternal origin of BRCA1 are diagnosed with BC earlier than BRCA1 mutation carriers with a maternal origin of the BRCA1 mutation, regardless of adjustment of year of inclusion and birth date. A novel finding is that BRCA1 mutation carriers with a paternal origin of mutation are older at age of ovarian cancer than BRCA1 mutation carriers with a maternal origin of mutation, regardless of adjustment of year of inclusion and birth date. There were no associations between age at BC or OvC diagnosis and parental origin in BRCA2 mutation carriers, but the number of carriers in our material was small. The difference might be due to co-inherited modifiers, either gene or parent specific. The clinical relevance of these finding is small, we see no need of a change in the screening programs available for BRCA1/2 mutation carriers at the moment. However, the parental difference is interesting from a biological stand point.
Citation Format: Carolina Ellberg, Helena Jernstrom, Per Broberg, Ake Borg, Hakan Olsson. Impact of parental origin of BRCA1/ 2 mutation on age at breast and ovarian cancer diagnosis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5047. doi:10.1158/1538-7445.AM2014-5047