Among the many data sources included in this meta-analysis, those from the Swedish population-based Family Cancer Database warrant special comment, as they are derived from a resource that contains 10.2 million individuals, among whom there are 182,000 fathers and 3,700 sons with medically verified prostate cancer. The size of this data set, with its near complete ascertainment of the entire Swedish population and objective verification of cancer diagnoses, should yield risk estimates that are both accurate and free of bias. The familial SIRs for prostate cancer were 2.4 (95% CI, 2.2-2.6), 3.8 (95% CI, 2.7-5.0), and 9.4 (95% CI, 5.8-14.0) for men with prostate cancer in their fathers only, brothers only, and both father and brother, respectively. The SIRs were even higher if the affected relative was diagnosed with prostate cancer before age 55 years. A separate analysis of this Swedish database reported that the cumulative (absolute) risks of prostate cancer among men in families with two or more affected cases were 5%, 15%, and 30% by ages 60, 70, and 80 years, respectively, compared with 0.45%, 3%, and 10% at the same ages in the general population. The risks were higher still if the affected father was diagnosed before age 70 years. The corresponding familial population attributable fractions (PAFs) were 8.9%, 1.8%, and 1.0% for the same three groups, respectively, yielding a total PAF of 11.6%; approximately 11.6% of all prostate cancer in Sweden can be accounted for on the basis of familial history of the disease.
Table 1. Relative Risk Related to Family History of Prostate Cancera
FDR = first-degree relative.
a Adapted from Zeegers et al.
||Relative Risk for Prostate Cancer
|Brother with prostate cancer diagnosed at any age
||3.4 (95% CI, 3.0-3.8)
|Father with prostate cancer diagnosed at any age
||2.2 (95% CI, 1.9-2.5)
|One affected FDR diagnosed at any age
||2.6 (95% CI, 2.3-2.8)
|One affected second-degree relative diagnosed at any age
||1.7 (95% CI, 1.1-2.6)
|Affected FDRs diagnosed age <65 years
||3.3 (95% CI, 2.6-4.2)
|Affected FDRs diagnosed age >65 years
||2.4 (95% CI, 1.7-3.6)
|Two or more affected FDRs diagnosed at any age
||5.1 (95% CI, 3.3-7.8)
Using data from the Nationwide Swedish Family-Cancer Database, age-specific hazard ratios (HR) for prostate cancer diagnosis and mortality were computed. The analysis was stratified by whether the father and/or brother(s) of affected men also had prostate cancer and by their age at diagnosis. The HRs increased with decreasing age at diagnosis for both fathers and male siblings. As expected, the HR for prostate cancer diagnosis was high in men with a father and two brothers with prostate cancer (HR = 10.86; 95% CI, 7.08-16.66) or with three brothers with prostate cancer (HR = 24.35; 95% CI, 16.18-36.64).