Three-generation familial risks in prostate cancer with a special focus on the early onset patients and their maternal and paternal relatives

Abstract

Background: Swedish nationwide family and cancer data extend through three generations providing a unique chance for study of familial cancer in PC between first-degree relatives (FDR) and second-degree relatives (SDR). It also enables a test for the usefulness of maternal family information.Methods: Familial relative risks (standardized incidence ratios, SIRs) for PC were calculated for young men in generation 3 when their brothers, fathers, uncles and grandparents were diagnosed with PC (they were probands).Results: Familial SIRs for two affected brothers were 4.0 but when additionally a SDR (uncle or grandfather) was affected SIR reached 10.3. When a father was the proband, SIR was 3.1 but when additionally a SDR was affected SIR reached 4.7, and risk increased up to 11.6 with increasing numbers of affected SDRs. Importantly, affected SDRs were more numerous than FDRs. When a maternal or paternal grandfather was the only proband SIR for both was about 1.6. Both maternal and paternal uncles transmitted a risk of 1.6, and when two uncles were affected SIR climbed to about 2.0. The highest familial risk of 27 was found for affected brothers with a father and 2 SDRs diagnosed with PC.Conclusions: The results showed that for the young patients in generation 3 the richest sources of familial probands were SDRs. The uncles belong to the generation of fathers, and they are likely to be more numerous than grandparents. Maternal and paternal SDRs are equally informative for genetic counseling and both parental lineages should be used as they provide equal familial information about the risks of PC.