Impact of a paternal origin of germline BRCA1/2 mutations on the age at breast and ovarian cancer diagnosis

abstract

Three studies have reported that BRCA1/2 mutations of paternal origin confer an earlier age at breast cancer diagnosis compared with maternal origin. The primary aim of this study was to investigate the impact of parental origin of BRCA1/2 mutations on age at breast and ovarian cancer diagnosis.

This study included 577 female BRCA1/2 mutation carriers. All BRCA1/2 mutation carriers belonged to families registered between 1993 and 2011 at the Oncogenetic Clinic at Skånes University Hospital, Lund, Sweden. Cox proportional hazard ratios were used to analyze time to breast or ovarian cancer diagnosis. A novel finding was that carriers of BRCA1 mutations of paternal origin were 4 years older at age of ovarian cancer (P = 0.009) compared with those carrying a BRCA1 mutation of maternal origin. BRCA1 carriers with mutations of paternal origin were 4 years younger at breast cancer diagnosis (P = 0.017) compared with those carrying a BRCA1 mutation of maternal origin, which is in agreement with three previous studies. Both findings were adjusted for of year of inclusion, birth date, and oral contraceptive pill use. No associations between parental origin of BRCA2 mutations and time to breast or ovarian cancer diagnosis were found. An attempt to handle a potential selection bias regarding use of oral contraceptives was made using multiple imputations by chained equations. The observed age difference may allow a greater understanding of mechanisms associated with the differences in cancer penetrance in BRCA1/2 mutation carriers, some of which may depend on paternal origin.