Results of a genome‐wide linkage analysis in prostate cancer families ascertained through the ACTANE consortium

Edwards, Steve; Meitz, Julia C.; Eles, Ros; Evans, Chris; Easton, Doug; Hopper, John L.; Giles, Graham G.; Foulkes, William D.; Narod, Steven A.; Simard, Jacques; Badzioch, Mike D.; Mahle, Lovise

doi:10.1002/pros.10301

Cited by 36 publications

(5 citation statements)

References 45 publications

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“…We hypothesized that SNPs may influence the generation of ERG fusion, which is an early event in CaP carcinogenesis. A genome-wide linkage analysis found that several loci located on chromosomes 9, 18, and X are associated with the development of fusion-positive prostate cancer; however, these studies were performed in familial prostate cancer [56,57].…”

Section: Discussionmentioning

confidence: 99%

Association of germline genetic variants with TMPRSS2-ERG fusion status in prostate cancer

Kohaar

Chen

et al. 2020

Oncotarget

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Introduction: Oncogenic activation of ERG resulting from TMPRSS2-ERG gene fusion is a key molecular genetic alteration in prostate cancer (CaP). The frequency of ERG fusion is variable by race; however, there are limited data available on germline polymorphisms associating with ERG fusion status. The goal of this study is to identify the inherited risk variants associating with ERG status of CaP. Materials and Methods: SNP genotyping was performed on the Illumina platform using Infinium Oncoarray SNP chip on blood derived genomic DNA samples from 400 patients treated by radical prostatectomy at a single military institution. ERG status was determined in whole mounted prostate specimens by immuno-histochemistry (IHC) for ERG protein expression. Data analysis approaches included association analyses based on EMMAX and imputation by IMPUTE2. Imputed SNPs were validated by ddPCR. Results: SNP genotyping analysis using imputation identified rs34349373 (p 4.68 × 10-8) and rs2055272 (p 5.62 × 10-8) in TBC1D22B to be significantly associated with ERG fusion status in index tumor and non-index tumor foci. Imputed SNP rs2055272 was further experimentally validated by ddPCR with 98.04% (100/102) concordance. Initial discovery analysis based on SNPs on Oncoarray SNP chip, showed significant (p 10-5) association for SNPs (rs6698333, rs1889877, rs3798999, rs10215144, rs3818136, rs9380660 and rs1792695) with ERG fusion status. The study also replicated two previously known ERG fusion associated SNPs (rs11704416 in chromsome 22; rs16901979 in chromosome 8). Conclusions: This study identified SNPs associated with ERG status of CaP. Impact: The findings may contribute towards defining the underlying genetics of ERG positive and ERG negative CaP patients.

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Section: Discussionmentioning

confidence: 99%

Association of germline genetic variants with TMPRSS2-ERG fusion status in prostate cancer

Kohaar

Chen

et al. 2020

Oncotarget

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“…We collected all germline BRCA variants reported in these studies. Some of these studies did not specify if these variants are variants of unknown significance (VUS) or pathogenetic [22,25,28,37,[39][40][41]46], as they reported only the overall number of identified mutations; other studies [31,34,38] included both VUS and pathogenetic germline BRCA variants. To provide additional information for further studies, when variants' nomenclature was available in the original study, we have revised these alterations in accord with the most recent ClinVar classification.…”

Section: Limitationsmentioning

confidence: 99%

Prevalence of Germline BRCA1/2 Variants in Ashkenazi and Non-Ashkenazi Prostate Cancer Populations: A Systematic Review and Meta-Analysis

Cioffi

Cobelli

Veronesi

et al. 2023

Cancers

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Background and aims: International guidelines recommend testing BRCA2 in men with prostate cancer, due to the presence of a strong association with this gene. Some ethnicities present disparities in genetic distribution for the relation with specific founder variants. Ashkenazi Jewish people are, importantly, at high risk of breast cancer for their inherited cluster with germline BRCA1/2 variants. However, in Ashkenazi men with prostate cancer, the prevalence of BRCA1 and/or BRCA2 is not well defined. We assessed the frequency of these variants in Ashkenazi vs. non-Ashkenazi men with prostate cancer. Materials and Methods: In accord with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, we revised all germline BRCA variants reported in MEDLINE from 1996 to 2021 in Ashkenazi and non-Ashkenazi men with prostate cancer. Results: Thirty-five original studies were selected for the analysis. Among populations from Israel and North America, Ashkenazi Jewish men presented higher prevalence of BRCA1 variants [0.9% (0.4–1.5) vs. 0.5% (0.2–1.1), p = 0.09] and a lower prevalence of BRCA2 variants [1.5% (1.1–2.0) vs. 3.5% (1.7–5.9), p = 0.08] in comparison to the non-Ashkenazi population. Conclusions: Since germline BRCA1 variants are more prevalent and BRCA2 variants are less prevalent in PCa patients of Ashkenazi Jewish ethnicity in comparison to non-Ashkenazi patients, prostate cancer genetic screening in Ashkenazi men should not be restricted to the BRCA2 gene.

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“…Thus far, several GWS have been reported for prostate cancer [ 1 , 3 , 5 , 57 - 72 ]. The significant results are summarised as follows:…”

Section: Genome Searches In Prostate Cancermentioning

confidence: 99%

“…7q, 19q [ 89 - 91 ]. Eight GWS have been published recently in one issue of the Prostate (ACTANE Consortium [ 72 ]; Lange et al [ 65 ]; Schleutker et al [ 66 ]; Cunningham et al [ 67 ]; Xu et al [ 68 ]; Wiklund et al [ 69 ]; Janer et al [ 70 ]; Witte et al [ 71 ], Dec 2003). A summary of these was published in an accompanying review by Easton (2003) [ 5 ].…”

Section: Genome Searches In Prostate Cancermentioning

confidence: 99%

The Clinical Genetics of Prostate Cancer

Kommu

Edwards

Eeles

2004

Hered Cancer Clin Pract

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Prostate cancer is the most common cancer in men and the second highest cause of cancer-related mortality in the U.K. A genetic component in predisposition to prostate cancer has been recognized for decades. One of the strongest epidemiological risk factors for prostate cancer is a positive family history. The hunt for the genes that predispose to prostate cancer in families has been the focus of many research groups worldwide for the past 10 years. Both epidemiological and twin studies support a role for genetic predisposition to prostate cancer. Familial cancer loci have been found, but the genes that cause familial prostate cancer remain largely elusive. Unravelling the genetics of prostate cancer is challenging and is likely to involve the analysis of numerous predisposition genes. Current evidence supports the hypothesis that excess familial risk of prostate cancer could be due to the inheritance of multiple moderate-risk genetic variants. Although research on hereditary prostate cancer has improved our knowledge of the genetic aetiology of the disease, a lot of questions still remain unanswered.This article explores the current evidence that there is a genetic component to the aetiology of prostate cancer and attempts to put into context the diverse findings that have been shown to be possibly associated with the development of hereditary prostate cancer. Linkage searches over the last decade are summarised. It explores issues as to why understanding the genetics of prostate cancer has been so difficult and why despite this, it is still a major focus of research. Finally, current and future management strategies of men with Hereditary Prostate Cancer (HPC) are discussed.

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Results of a genome‐wide linkage analysis in prostate cancer families ascertained through the ACTANE consortium

Abstract: Genetic susceptibility to prostate cancer is likely to be controlled by many loci, with no single gene explaining a large fraction of the familial risk. Pooling of results from all available genome scans is likely to be required to obtain definitive linkage results.

Cited by 36 publications

References 45 publications

Association of germline genetic variants with TMPRSS2-ERG fusion status in prostate cancer

Association of germline genetic variants with TMPRSS2-ERG fusion status in prostate cancer

Prevalence of Germline BRCA1/2 Variants in Ashkenazi and Non-Ashkenazi Prostate Cancer Populations: A Systematic Review and Meta-Analysis

The Clinical Genetics of Prostate Cancer

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