Mapping Interactive Cancer Susceptibility Genes in Prostate Cancer

2007 ◽  
Author(s):  
Theodore G. Krontiris ◽  
Garry P. Larson ◽  
Yan Ding
Keyword(s):  
Prostate Cancer ◽  
Cancer Susceptibility ◽  
Susceptibility Genes ◽  
Cancer Susceptibility Genes

Replication linkage study for prostate cancer susceptibility genes

The Prostate ◽  
2000 ◽  
Vol 45 (2) ◽  
pp. 106-114 ◽  
Author(s):  
Brian K. Suarez ◽  
Jennifer Lin ◽  
John S. Witte ◽  
David V. Conti ◽  
Martin I. Resnick ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Susceptibility ◽  
Susceptibility Genes ◽  
Linkage Study ◽  
Cancer Susceptibility Genes ◽  
Prostate Cancer Susceptibility

Prostate cancer susceptibility genes: lessons learned and challenges posed.

2003 ◽  
pp. 225-259 ◽  
Author(s):  
J Simard ◽  
M Dumont ◽  
D Labuda ◽  
D Sinnett ◽  
C Meloche ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Genetic Variants ◽  
Cancer Susceptibility ◽  
Susceptibility Genes ◽  
Screening Methods ◽  
Cancer Susceptibility Genes ◽  
Prostate Cancer Susceptibility ◽  
Common Genetic Variants

In most developed countries, prostate cancer is the most frequently diagnosed malignancy in men. The extent to which the marked racial/ethnic difference in its incidence rate is attributable to screening methods, environmental, hormonal and/or genetic factors remains unknown. A positive family history is among the strongest epidemiological risk factors for prostate cancer. It is now well recognized that the role of candidate genetic markers to this multifactorial malignancy is more difficult to identify than the identification of other cancer susceptibility genes. Indeed, despite the localization of several susceptibility loci, there has been limited success in identifying high-risk susceptibility genes analogous to BRCA1 or BRCA2 for breast and ovarian cancer. Nonetheless, three strong candidate susceptibility genes have been described, namely ELAC2 (chromosome 17p11/HPC2 region), 2'-5'-oligoadenylate-dependent ribonuclease L (RNASEL), a gene in the HPC1 region, and Macrophage Scavenger Receptor 1 (MSR1), a gene within a region of linkage on chromosome 8p. Additional studies using larger cohorts are needed to fully evaluate the role of these susceptibility genes in prostate cancer risk. It is also of interest to mention that a significant percentage of men with early-onset prostate cancer harbor germline mutation in the BRCA2 gene thus confirming its role as a high-risk prostate cancer susceptibility gene. Although initial segregation analyses supported the hypothesis that a number of rare highly penetrant loci contribute to the Mendelian inheritance of prostate cancer, current experimental evidence better supports the hypothesis that some of the familial risks may be due to inheritance of multiple moderate-risk genetic variants. In this regard, it is not surprising that analyses of genes encoding key proteins involved in androgen biosynthesis and action led to the observation of a significant association between a susceptibility to prostate cancer and common genetic variants in some of those genes.

Genome-wide scan for prostate cancer susceptibility genes in the Johns Hopkins hereditary prostate cancer families

The Prostate ◽  
2003 ◽  
Vol 57 (4) ◽  
pp. 320-325 ◽  
Author(s):  
Jianfeng Xu ◽  
Elizabeth M. Gillanders ◽  
Sarah D. Isaacs ◽  
Bao-li Chang ◽  
Kathy E. Wiley ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Susceptibility ◽  
Susceptibility Genes ◽  
Hereditary Prostate Cancer ◽  
Cancer Susceptibility Genes ◽  
Prostate Cancer Susceptibility ◽  
Genome Wide ◽  
Genome Wide Scan

scholarly journals Prostate cancer susceptibility genes on 8p21–23 in a Dutch population

2013 ◽  
Vol 16 (3) ◽  
pp. 248-253 ◽  
Author(s):  
M P Zeegers ◽  
D Nekeman ◽  
H S Khan ◽  
B A C van Dijk ◽  
R A Goldbohm ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Susceptibility ◽  
Susceptibility Genes ◽  
Dutch Population ◽  
Cancer Susceptibility Genes ◽  
Prostate Cancer Susceptibility

scholarly journals A Systems Genetics Approach Identifies CXCL14, ITGAX, and LPCAT2 as Novel Aggressive Prostate Cancer Susceptibility Genes

PLoS Genetics ◽  
2014 ◽  
Vol 10 (11) ◽  
pp. e1004809 ◽  
Author(s):  
Kendra A. Williams ◽  
Minnkyong Lee ◽  
Ying Hu ◽  
Jonathan Andreas ◽  
Shashank J. Patel ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Susceptibility ◽  
Susceptibility Genes ◽  
Systems Genetics ◽  
Aggressive Prostate Cancer ◽  
Cancer Susceptibility Genes ◽  
Prostate Cancer Susceptibility

Characterization of findings on prostate cancer tumor sequencing that should prompt consideration for germline testing.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5022-5022
Author(s):  
Hong Truong ◽  
Kelsey Breen ◽  
Yelena Kemel ◽  
Andrew Thomas Lenis ◽  
Peter Reisz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Germline Mutation ◽  
Cancer Susceptibility ◽  
Germline Mutations ◽  
Susceptibility Genes ◽  
Study Cohort ◽  
Targeted Next Generation Sequencing ◽  
Cancer Susceptibility Genes ◽  
Tumor Sequencing ◽  
Germline Testing

5022 Background: Tumor sequencing is increasingly used for therapeutic selection in men with advanced prostate cancer (PC). If tumor-only sequencing is performed without matched germline, identified mutations could be of somatic or germline origin. Germline mutations could confer additional risk for other cancers to the patient and at-risk family members. The objective of this study is to determine the overall and gene-specific probability of pathogenic/likely pathogenic germline mutations based on tumor-only sequencing. Methods: We investigated mutations found in a cohort of men with PC who underwent targeted next generation sequencing of PC tumor and matched peripheral blood using the MSK-IMPACT assay between 01/2015 and 01/2020. A germline probability for each gene was determined by dividing the number of germline mutations by the total number of somatic and germline mutations. Cancer susceptibility genes commonly sequenced on tumor-based tests for PC were assessed, including ATM, BRCA1/ 2, BRIP1, CHEK2, HOXB13, MLH1, MSH2, MSH6, NBN, PALB2, PMS2 (henceforth referred to as PC genes). Results: A total of 1883 men with PC were included, with median age of diagnosis of 62.0 ± 8.8 years. 84% had high risk PC, 52% had metastasis, 38% had family history of PC. A total of 364 (19%) men had at least one mutation (either somatic or germline) in PC genes. Overall, 189 (10%) men had at least one germline mutation that would not have been reported as germline without matched normal. The average germline probability of PC genes was 40% (range: 0% in MLH1 to 83% in CHEK2). The number of total mutations, germline mutations, and germline probability of genes found in > 0.5% of the study cohort are summarized in Table. All these genes are moderate/high penetrance autosomal dominant genes with established guidelines for cascade testing, enhanced cancer screening, or potential risk-reducing surgery. Conclusions: In this study, an average of 40% of mutations found in cancer susceptibility genes on PC tumor sequencing were germline mutations. Men undergoing tumor-only sequencing should be counseled on the possibility of uncovering a germline mutation. In addition to BRCA1/ 2, mutations in certain genes, such as CHEK2 and PALB2, have a high probability of being germline and should prompt referral for genetic counseling and germline testing.[Table: see text]

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