An Epidemiological Reappraisal of the Familial Aggregation of Prostate Cancer: A Meta-Analysis

Abstract

Studies on familial aggregation of cancer may suggest an overall contribution of inherited genes or a shared environment in the development of malignant disease. We performed a meta-analysis on familial clustering of prostate cancer. Out of 74 studies reporting data on familial aggregation of prostate cancer in unselected populations retrieved by a Pubmed search and browsing references, 33 independent studies meeting the inclusion criteria were used in the analysis performed with the random effects model. The pooled rate ratio (RR) for first-degree family history, i.e. affected father or brother, is 2.48 (95% confidence interval: 2.25-2.74). The incidence rate for men who have a brother who got prostate cancer increases 3.14 times (CI: 2.37-4.15), and for those with affected father 2.35 times (CI: 2.02-2.72). The pooled estimate of RR for two or more affected first-degree family members relative to no history in father and in brother is 4.39 (CI: 2.61-7.39). First-degree family history appears to increase the incidence rate of prostate cancer more in men under 65 (RR: 2.87, CI: 2.21-3.74), than in men aged 65 and older (RR: 1.92, CI: 1.49-2.47), p for interaction = 0.002. The attributable fraction among those having an affected first-degree relative equals to 59.7% (CI: 55.6-63.5%) for men at all ages, 65.2% (CI: 57.7-71.4%) for men younger than 65 and 47.9% (CI: 37.1-56.8%) for men aged 65 or older. For those with a family history in 2 or more first-degree family members 77.2% (CI: 65.4-85.0%) of prostate cancer incidence can be attributed to the familial clustering. Our combined estimates show strong familial clustering and a significant effect-modification by age meaning that familial aggregation was associated with earlier disease onset (before age 65).