Three‐generation familial risks in early‐onset prostate cancer with maternal and paternal relatives

OBJECTIVES: To study familial prostate cancer (PCa) between first-degree relatives (FDRs) and second-degree relatives (SDRs), we accessed Swedish nationwide family and cancer data that extended through three generations and thus providing a unique chance for study of familial cancer in PCa between close and distant relatives (SDRs). The specific aim was to show the usefulness of data on maternal and paternal uncles and grandfathers for risk assessment on young patients with PCa. PATIENTS AND METHODS: Familial relative risks (standardised incidence ratios [SIRs]) for PCa were calculated for young men (aged <69 years) in the third generation when their brothers, fathers, uncles and grandparents were diagnosed with PCa (they were probands). RESULTS: Familial SIRs for two affected brothers were 4.1 but when, additionally a SDR (uncle or grandfather) was affected SIR reached 10.1. 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 11.5 with increasing numbers of affected SDRs. Patients with affected SDRs were more numerous than those with affected FDRs. When a maternal or paternal grandfather was the only proband the SIR for both was about 1.6. Maternal and paternal uncles transmitted a risk of 1.8 and 1.5, respectively, and when two uncles were affected, the SIR climbed to about 2.0. The highest familial risk of 27 was found for affected brothers with a father and two SDRs diagnosed with PCa. CONCLUSIONS: The results showed that for the young patients in the third generation 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 counselling and both parental lineages should be used as they provide equal familial information about the risks of PCa.