Dataset Information

A genome screen of families with multiple cases of prostate cancer: evidence of genetic heterogeneity.

ABSTRACT: We conducted a genomewide screen for prostate cancer-susceptibility genes on the basis of data from 98 families from the United States and Canada that had three or more verified diagnoses of prostate cancer among first- and second-degree relatives. We found a statistically significant excess of markers for which affected relatives exhibited modest amounts of excess allele-sharing; however, no single chromosomal region contained markers with excess allele-sharing of sufficient magnitude to indicate unequivocal evidence of linkage. Positive linkage signals of nominal statistical significance were found in two regions (5p-q and 12p) that have been identified as weakly positive in other data sets and in region 19p, which has not been identified previously. All these signals were considerably stronger for analyses restricted to families with mean age at onset below the median than for analyses of families with mean age at onset above the median. The data provided little support for any of the putative prostate cancer-susceptibility genes identified in other linkage studies.

SUBMITTER: Hsieh CL

PROVIDER: S-EPMC1226029 | biostudies-literature | 2001 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A genome screen of families with multiple cases of prostate cancer: evidence of genetic heterogeneity.

Hsieh C L CL Oakley-Girvan I I Balise R R RR Halpern J J Gallagher R P RP Wu A H AH Kolonel L N LN O'Brien L E LE Lin I G IG Van Den Berg D J DJ Teh C Z CZ West D W DW Whittemore A S AS

American journal of human genetics 20010612 1

We conducted a genomewide screen for prostate cancer-susceptibility genes on the basis of data from 98 families from the United States and Canada that had three or more verified diagnoses of prostate cancer among first- and second-degree relatives. We found a statistically significant excess of markers for which affected relatives exhibited modest amounts of excess allele-sharing; however, no single chromosomal region contained markers with excess allele-sharing of sufficient magnitude to indica ...[more]

PMID: 11404817

Similar Datasets

Project description:BackgroundRare germline mutations in DNA repair genes are associated with prostate cancer (PCa) predisposition and prognosis.ObjectiveTo quantify the frequency of germline DNA repair gene mutations in UK PCa cases and controls, in order to more comprehensively evaluate the contribution of individual genes to overall PCa risk and likelihood of aggressive disease.Design, setting, and participantsWe sequenced 167 DNA repair and eight PCa candidate genes in a UK-based cohort of 1281 young-onset PCa cases (diagnosed at ≤60yr) and 1160 selected controls.Outcome measurements and statistical analysisGene-level SKAT-O and gene-set adaptive combination of p values (ADA) analyses were performed separately for cases versus controls, and aggressive (Gleason score ≥8, n=201) versus nonaggressive (Gleason score ≤7, n=1048) cases.Results and limitationsWe identified 233 unique protein truncating variants (PTVs) with minor allele frequency <0.5% in controls in 97 genes. The total proportion of PTV carriers was higher in cases than in controls (15% vs 12%, odds ratio [OR]=1.29, 95% confidence interval [CI] 1.01-1.64, p=0.036). Gene-level analyses selected NBN (pSKAT-O=2.4×10-4) for overall risk and XPC (pSKAT-O=1.6×10-4) for aggressive disease, both at candidate-level significance (p<3.1×10-4 and p<3.4×10-4, respectively). Gene-set analysis identified a subset of 20 genes associated with increased PCa risk (OR=3.2, 95% CI 2.1-4.8, pADA=4.1×10-3) and four genes that increased risk of aggressive disease (OR=11.2, 95% CI 4.6-27.7, pADA=5.6×10-3), three of which overlap the predisposition gene set.ConclusionsThe union of the gene-level and gene-set-level analyses identified 23 unique DNA repair genes associated with PCa predisposition or risk of aggressive disease. These findings will help facilitate the development of a PCa-specific sequencing panel with both predictive and prognostic potential.Patient summaryThis large sequencing study assessed the rate of inherited DNA repair gene mutations between prostate cancer patients and disease-free men. A panel of 23 genes was identified, which may improve risk prediction or treatment pathways in future clinical practice.

Dataset Information

A genome screen of families with multiple cases of prostate cancer: evidence of genetic heterogeneity.

Publications

A genome screen of families with multiple cases of prostate cancer: evidence of genetic heterogeneity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets