Clinical course of early onset prostate cancer with special reference to family history as a prognostic factor

1999 ◽  
Vol 9 (1) ◽  
pp. 74
Author(s):  
Bob Djavan
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
Prognostic Factor ◽  
Special Reference ◽  
Early Onset ◽  
Clinical Course

Clinical Course of Early Onset Prostate Cancer with Special Reference to Family History as a Prognostic Factor

1998 ◽  
Vol 34 (1) ◽  
pp. 19-24 ◽  
Author(s):  
Ola Bratt ◽  
Ulf Kristoffersson ◽  
Håkan Olsson ◽  
Rolf Lundgren
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
Prognostic Factor ◽  
Special Reference ◽  
Early Onset ◽  
Clinical Course

Family history is significantly associated with prostate cancer and its early onset in Chinese population

The Prostate ◽  
2019 ◽  
Vol 79 (15) ◽  
pp. 1762-1766 ◽  
Author(s):  
Yang Xu ◽  
Da Huang ◽  
Yishuo Wu ◽  
Dingwei Ye ◽  
Ning Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
Early Onset ◽  
Chinese Population

Germline DNA damage repair gene alterations in Chinese prostate patients: More than HRR and MMR.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13041-e13041
Author(s):  
Junlong Wu ◽  
Yu Wei ◽  
Changbin Zhu ◽  
Bo Dai ◽  
Xiaojian Qin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
Cancer Patients ◽  
Early Onset ◽  
Excision Repair ◽  
Parp Inhibitors ◽  
Male Population ◽  
Repair Gene ◽  
Germline Variants ◽  
Significant Difference

e13041 Background: Prostate cancer is a worldwide most occurred malignancy in male population. Genetic aberrations of homologous recombination repair (HRR) pathway were proved to be associated with aggressive disease and poorer outcome but may also lead cancer cells more vulnerable to PARP inhibitors. Other than HRR, germline variants in mismatch repair (MMR), nucleotide excision repair (NER) were also identified. Thus, it is important to clarify the distribution of germline alterations of DDR pathways in Chinese prostate cancer patients. Methods: Sixty-five prostate cancer patients unselected for family history, stage of disease, or age at diagnosis were collected. DNA from peripheral blood was extracted. Whole-exon was captured and sequenced subsequently using MGI-SEQ 2000 platform. A total of 229 DDR genes were selected for further analysis. Germline variants were determined to be deleterious according to the ACMG 2015 guidelines. Results: Ten of 65 patients (15.38%) had 7 pathogenic/likely pathogenic germline variants involving 5 different genes: FANCD2 (n = 5), BRCA2 (n = 3), CHEK2 (n = 1), ATM (n = 1) and RECQL (n = 1). Nine patients (13.84%) carried variants predicated to be deleterious via in silico predicators. Taken together, deleterious/potential deleterious germline variants were categorized into 5 DDR pathways which were Fanconi Anemia (9.2%), HRR (9.2%), MMR (4.6%), BER (4.6%) and NER (1.5%). Patients with pathogenic/likely pathogenic germline variants had tendency to be early-onset (mean age [range] at diagnosis, 52[43-67] versus 64[37-80] years, P = 0.001). PSA level at initial diagnosis and self-reported family history did not have significant difference between deleterious mutation carriers and non-carriers (P = 0.396 for PSA level, P = 0.753 for family history). Moreover, metastasis and Gleason score were not associated with deleterious germline variants. Conclusions: Our data showed approximately 52% DDR mutation occurred in other DNA repair pathways besides HRR and MMR, which was a unique spectrum of germline variants in Chinese prostate cancer patients. This indicated distinct genetic etiology and potential therapeutic targets of prostate cancer in Chinese population. Moreover, early-onset in patients with deleterious germline variants is an important clinical character. Whole DDR pathway genes’ testing and counseling should be considered for application for young individuals.

Germline mutations in DNA damage repair genes and HOXB13 among African American men diagnosed with early-onset prostate cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10505-10505
Author(s):  
Jennifer Lynn Beebe-Dimmer ◽  
Christopher Sample ◽  
Tara Baird ◽  
Azita Sadeghpour ◽  
Julie J. Ruterbusch ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Damage ◽  
African American ◽  
Family History ◽  
High Risk ◽  
Early Onset ◽  
African American Men ◽  
Damage Repair ◽  
High Risk Disease ◽  
Repair Genes

10505 Background: Inherited defects in DNA damage repair (DDR) genes (e.g. ATM, BRCA1/2) and the tumor suppresser gene HOXB13 are rare in the general population, but have been observed at a higher rate among men with early-onset and advanced prostate cancer. However, most studies include few, if any, African American men, highlighting the need to understand the contribution of mutations in these genes in this high-risk population. Methods: A population-based cohort of 757 African American men diagnosed with prostate cancer at age 62 years or younger were identified and enrolled through the Metropolitan Detroit Cancer Surveillance System (MDCSS), one of NCI’s founding members of the SEER program. Participants completed a short survey to collect information on family history, medical history (including cancer-related treatment), surveillance, and health behaviors. Each participant submitted a saliva or blood sample for genetic analyses and consent for tumor tissue if available. All clinical data were collected through linkage with the MDCSS registry. Full exome sequencing was performed and herein, we report the mutation patterns observed in a panel of DNA repair genes and HOXB13. All variants were ranked according to frequency (MAF < 1%); REVEL, SIFT and PolyPhen scores for pathogenic potential; evidence from existing literature; and prevalence in the cohort. Results: Among the 744 African American prostate cancer cases with adequate DNA for sequencing and thus included in this analysis, the mean age at diagnosis was 55.6 years, 29% reported a family history of prostate cancer in a first degree family member, and 40% were initially diagnosed with intermediate- to high-risk disease (stage T3/T4 and/or Gleason 4+3 and higher at diagnosis). We identified 20 variants that were either known or predicted to be pathogenic in 11 candidate genes ( ATM, ATR, BRCA1/2, BRIP1, CHEK2, FANCA, HOXB13, MSH2, PALB2, and PMS2). These particular variants were more common among men diagnosed before age 55 and in men with high grade cancer in this cohort. Conclusions: Our results suggest that mutations in DDR genes and HOXB13 may be important cancer risk factors for African American men diagnosed with early-onset and intermediate- to high-risk disease. Further study is necessary to describe the spectrum and prevalence of genetic mutations in this population including the characterization of variants of unknown significance.

scholarly journals Clonal evaluation of early onset prostate cancer by expression profiling of ERG, SPINK1, ETV1, and ETV4 on whole mount radical prostatectomy tissue

2019 ◽  
Author(s):  
Zhichun Lu ◽  
Sean R. Williamson ◽  
Shannon Carskadon ◽  
Pavithra D. Arachchige ◽  
Gaury Dhamdhere ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
Radical Prostatectomy ◽  
Prostate Specific Antigen ◽  
Early Onset ◽  
Biochemical Recurrence ◽  
African American Men ◽  
Expression Profiles ◽  
Specific Antigen ◽  
Whole Mount

ABSTRACTExpression profiles of ETS related genes and SPINK1 in early onset prostate cancer have not been thoroughly explored. We retrieved 151 radical prostatectomy specimens from young men with prostate cancer (<55yrs) and characterized the expression of ERG, SPINK1, ETV1 and ETV4 by dual immunohistochemistry and dual RNA in-situ hybridization. Age, race, family history, preoperative prostate-specific antigen, biochemical recurrence and pathological variables using whole mount radical prostatectomy tissue were collected. 313 tumor nodules from 151 men including 68 (45%) Caucasians and 61 (40%) African Americans. Positive family history of prostate cancer was observed in 65 (43%) patients. Preoperative prostate-specific antigen ranged from 0.3 to 52.7 ng/ml (mean 7.04). Follow-up period ranged from 1 to 123.7 months (Mean 30.3). Biochemical recurrence was encountered in 8/151 (5%). ERG overexpression was observed in 85/151 (56%) cases, followed by SPINK1 in 61/151 (40%), ETV1 in 9/149 (6%), and ETV4 in 4/141 (3%). There were 25/151 (17%) cases showing both ERG and SPINK1 overexpression within different regions of either the same tumor focus or different foci. Higher frequency of ERG overexpression was seen in younger patients (≤ 45 years old) (76% vs. 49%, p = 0.002213), Caucasian men (71% vs. 41% p = 0.000707), organ-confined tumors (64% vs. 33%, p = 0.00079), and tumors of Grade Groups 1 and 2 (62% vs. 26%, p = 0.008794). SPINK1 overexpression was more in African American men (68% vs. 26%, p = 0.00008), in tumors with high tumor volume (> 20%) and with anterior located tumors. ETV1 and ETV4 demonstrated rare overexpression in these tumors, particularly in the higher-grade tumors. This study expands the knowledge of the clonal evolution of multifocal cancer in young patients and support differences in relation to racial background and genetics of prostate cancer.

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