Familial risks in 317,000 prostate cancer patients in relation to metastases and survival guiding diagnostics

Abstract

Background: Swedish nationwide family and cancer data offer the largest global resource for study of familial cancer. We focus here on familial risks in prostate cancer (PC) with questions on risk in individuals from families of multiple affected members and association of familial risk with metastatic disease and survival.Methods: Familial relative risk (standardized incidence ratio, SIR) was calculated to men in the second generation when their fathers, brothers or sons had PC.Results: A large proportion (69.3%) of the families presented with a single man diagnosed with PC; the proportion of multi-case families declined from 24.6% (2 PCs), 5.1% (3 PCs) and 1.1% (4 or more PCs). Familial SIRs ranged from 1.88 (15,000 father-son pairs) to 41.8 (cases in three2 generations). Age-incidence curves showed successively higher rates for men from multi-case families. Older PC patients had the highest proportion of metastases at diagnosis but in each age-group familial patients presented with a lower proportion of metastases compared to non-familial cases. Among brothers, the proportion of metastasis was higher in brothers first diagnosed compared to brothers with subsequent diagnosis. Men in multi-case families survived better than non-familial patients.Conclusions and clinical implications: The largest family study yet conducted on PC found two or more affected cases in 35,200 families. Risk varied greatly by family constellations, emphasizing the need for a detailed family history at diagnosis as basis for clinical decision making and genetic counseling. The reported high risks should encourage implementation of familial risk into schemes for PC screening.