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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).

SUBMITTER: Kicinski M

PROVIDER: S-EPMC3205054 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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An epidemiological reappraisal of the familial aggregation of prostate cancer: a meta-analysis.

Kiciński Michał M Vangronsveld Jaco J Nawrot Tim S TS

PloS one 20111031 10

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 effe ...[more]

PMID: 22073129

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Project description:The RNASEL gene on chromosome 1q25 was recently identified as a candidate gene for hereditary prostate cancer (PC). To confirm these findings, we screened 326 patients from 163 families with familial PC for potential germline mutations, by use of conformation-sensitive gel electrophoresis, followed by direct sequence analysis. A total of six variants were identified, including one intronic and five exonic changes (three missense and two silent alterations). There were no unequivocal pathogenic changes. To further test for potential associations between genes and increased risk for disease, the three missense polymorphisms (Ile97Leu, Arg462Gln, and Glu541Asp) were genotyped in 438 patients with familial PC and in 510 population-based control subjects. Association testing revealed no significant differences between patients and control subjects for either the Leu97 variant (chi(2) trend test = 1.42; P=.23) or the Asp541 variant (chi2=1.52; P=.22). However, significant differences were detected for the Arg462Gln genotypes (chi2=5.20; P=.02; odds ratio [OR] = 0.54; 95% confidence interval [CI] 0.32-0.91) when the genotype Gln/Gln was compared with Arg/Arg. In subset analyses, associations were also observed in the younger group (age at diagnosis </=64 years) (P=.0008; OR=0.29; 95% CI = 0.13-0.66), in node-negative patients (P=.01; OR=0.48; 95% CI 0.27-0.84), patients with stage T(1)/T(2) disease (P=.008; OR=0.39; 95% CI 0.2-0.75), and patients with low-grade disease (P=.01; OR=0.40; 95% CI 0.20-0.78). To evaluate whether this variant was also associated with sporadic PC, we genotyped an additional 499 patients with sporadic PC. Differences in frequency were not detected between patients with sporadic disease and control subjects. However, the same association was observed between patients with familial disease and patients with sporadic disease for the entire group (chi2=4.82; P=.03), as well as in the subset analyses. These results suggest that polymorphic changes within the RNASEL gene may be associated with increased risk of familial but not sporadic PC.

Dataset Information

An epidemiological reappraisal of the familial aggregation of prostate cancer: a meta-analysis.

Publications

An epidemiological reappraisal of the familial aggregation of prostate cancer: a meta-analysis.

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