Authors A Brandt, JL Bermejo, J Sundquist, K Hemminki
Review Date Mar 2010
Citation European Urology 2010; doi:10.1016/j.eururo.2010.02.002 (online)
Family history is a well-established risk factor for prostate cancer (PCa) although no high-risk genes have yet been identified. Some low-risk gene variants have been identified but are not used in clinical practice. The detailed assessment of familial PCa risk is therefore important for clinical counselling and screening recommendations.
The aim of this study was to determine the age-specific risks of PCa and the risk of death from PCa according to the number, type (father or brother) and the age of affected first-degree relatives using comprehensive population databases in Sweden.
Design, setting, and participants: The nationwide Swedish Family-Cancer Database includes a record of >11.8 million individuals and their cancers from 1958 to 2006. All men from the database with identified parents (>3.9 million individuals) were followed between 1961 and 2006. The study included 26,651 PCa patients, of whom 5,623 were familial.
Measurements: The age-specific hazard ratios (HRs) of PCa and the HRs of death from PCa were calculated according to the number and age of affected fathers and brothers.
The HRs for PCa diagnosis (compared to men with no family history) increased with the number of affected relatives (for example HR=2.9 for a man under 55 years of age with an affected father compared with HR=11.3 when there was an affected father and brother). HRs decreased with increasing age (for example an affected brother was associated with HR=4.4 for a man under 55 years of age compared with 2.6 for men 65-74 years old).
The highest HRs were observed for men <65 yr of age with three affected brothers (HR ~ 23) and the lowest for men between 65 and 74 yr of age with an affected father (HR = 1.8).
The HRs increased with decreasing paternal or fraternal diagnostic age. The pattern of the risk of death from familial PCa was similar to that for PCa incidence.
The present results can help to guide clinical counselling, particularly with respect to PSA testing. The results demonstrate the greatly increased risk when multiple first-degree relatives are affected. Also the increased risk conferred by family history is greater for younger men than older. A limitation of the study is that age-specific absolute risks are not reported.
Points to Note
- The number and type (father and/or brother) of affected family members are associated with the level of increased risk of prostate cancer, particularly for men under the age of 55.
- A lower age at diagnosis in the affected relative is associated with a higher level of risk.
- An affected brother conferred a higher risk than an affected father and this has been shown in other studies.
- These risk estimates can be helpful in counselling men about their risk of prostate cancer or risk of dying from prostate cancer compared to men with no family history.
- Family history is a stronger determinant of increased risk in younger men than older but this should be considered in the light of background risk of prostate cancer according to age.