Letter to the Editor: “Family history and pathogenic/likely pathogenic germline variants in prostate cancer patients”

The Prostate ◽  
2021 ◽  
Vol 81 (15) ◽  
pp. 1261-1261
Author(s):  
Fabrizio Di Maida ◽  
Antonio A. Grosso ◽  
Andrea Minervini
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
Cancer Patients ◽  
Germline Variants ◽  
Letter To The Editor

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.

Diagnostic yield of germline genetic testing following tumor testing in prostate cancer patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1591-1591
Author(s):  
Kingshuk Das ◽  
Stephen E Lincoln ◽  
Nhu Ngo ◽  
Daniel Esteban Pineda Alvarez ◽  
Shan Yang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
Cancer Patients ◽  
Diagnostic Yield ◽  
Significant Proportion ◽  
Consecutive Series ◽  
Primary Malignancy ◽  
Germline Variants ◽  
Nccn Guidelines ◽  
Germline Testing

1591 Background: NCCN guidelines recommend germline testing for patients with localized or advanced prostate cancer meeting family history or clinical/pathologic criteria. However, the guidelines for somatic molecular analysis generally consider advanced disease only, primarily to inform therapy. As the analytical and clinical specifications of both testing modalities differ accordingly, we examined the results of germline testing following prior somatic testing. Methods: We reviewed somatic and germline variants in an otherwise unselected consecutive series of patients who: (a) had a current or previous diagnosis of prostate cancer; (b) had undergone tumor sequencing; and (c) were referred for germline testing. Indications for germline testing included: potential germline origin of somatic test result, treatment or surgical planning, personal or family history, and patient concern. Results: 208 patients met study criteria of whom 81 (39%) harbored a pathogenic germline variant (PGV) in a cancer predisposition gene. Certain genes were more likely to harbor germline variants, and 98% (81) of PGVs were potentially actionable (Table). 9.6% of PGVs were not reported by somatic testing, reflecting analytical limitations of the somatic testing. Of note, 11 patients (14%) had PGVs identified after diagnosis of a subsequent primary malignancy. Conclusions: The high PGV rate of 39% was unexpected, given reported rates of 11.8% in patients with metastatic prostate cancer and 6% in high-risk localized disease (NCCN)--even considering potential clinician ascertainment bias. This finding, the potential clinical utility of 98% of PGVs identified, the significant proportion unreported by somatic testing, and the fraction of patients diagnosed with a PGV after a subsequent malignancy all suggest that germline testing is an underutilized tool in the care of prostate cancer patients and their families. [Table: see text]

Family history and pathogenic/likely pathogenic germline variants in prostate cancer patients

The Prostate ◽  
2021 ◽  
Vol 81 (7) ◽  
pp. 427-432
Author(s):  
Rachel A. Sabol ◽  
Elisa M. Ledet ◽  
Ellen Jaeger ◽  
Whitley Hatton ◽  
Marcus Moses ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
Cancer Patients ◽  
Germline Variants

421 PSYCHOSOCIAL DISTRESS IN PROSTATE CANCER PATIENTS: DOES FAMILY HISTORY MAKE A DIFFERENCE?

2011 ◽  
Vol 10 (2) ◽  
pp. 146
Author(s):  
K. Herkommer ◽  
A. Dinkel ◽  
M. Kornmayer ◽  
P. Herschbach ◽  
J.E. Gschwend
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
Cancer Patients ◽  
Psychosocial Distress

Impact of a changing population structure and clustering of cancer in prostate cancer patients depending on a first-degree family-history

2019 ◽  
Vol 18 (1) ◽  
pp. e1537
Author(s):  
K. Herkommer ◽  
R. Bittner ◽  
V.H. Meissner ◽  
M. Kron ◽  
S. Schiele ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Population Structure ◽  
Family History ◽  
Cancer Patients

PSA levels in unaffected first degree relatives of prostate cancer patients are higher than in men without family history of the disease

2002 ◽  
Vol 1 (1) ◽  
pp. 75
Author(s):  
A. Valerie ◽  
L. Cormier ◽  
G. Cancel-Tassin ◽  
M. Giordanella ◽  
M. Kuntz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
Cancer Patients ◽  
First Degree Relatives ◽  
History Of

Prevalence of pathogenic germline variants in DNA repair by race, age, and ethnicity in men with prostate cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5062-5062
Author(s):  
Alexandria Mara ◽  
Jason Zhu ◽  
Yuan Wu ◽  
Tom Callis ◽  
Shan Yang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
Advanced Prostate Cancer ◽  
Final Analysis ◽  
The United States ◽  
National Study ◽  
Germline Variants ◽  
Variant Of Uncertain Significance ◽  
Race Ethnicity ◽  
Germline Testing

5062 Background: Patients with advanced prostate cancer (PC) frequently harbor pathogenic or likely pathogenic (P/LP) germline variants (GVs) in mismatch repair (MMR) and homologous repair (HR) enzymes which have clinical and treatment implications. However, whether the prevalence of such GVs differ by race, ethnicity, family history, or age is unknown in men with PC. Methods: This is a retrospective analysis of germline DNA from men with PC in the United States, tested by Invitae. Baseline characteristics including self-identified race, ethnicity, family history (FH), and age were recorded. Race and ethnicity were analyzed by 3 cohorts: non-Ashkenazi Caucasian Americans (CA), non-Ashkenazi African Americans (AA), and Ashkenazi Jewish Americans (AJ). Chi-square testing was performed to identify significant differences across these categories between the three cohorts, with respect to combined and individual pathogenic MMR (MSH2/6, MLH1, PMS2, and MUTYH) and HR genes (BRCA1/2, ATM, CHEK2, RAD51D, and PALB2). Results: 3057 men were included in the final analysis: 2248 (74%) men were CA, 229 (7%) were AA, and 210 (7%) were AJ. Of these, 2665 (87%) men had a FH of PC and 463 (15%) had a P/LP GV. In addition, 1068 (35%) were found to have a variant of uncertain significance, and 35 (1.6%) had the HOXB13 G84E variant. There were no significant differences in the overall prevalence of MMR (CA 1.5% vs AA 0.9% vs AJ 1.4%, p = 0.89) or HR genes (CA 7.8% vs AA 7.9% vs AJ 10.5%, p = 0.37) by race/ethnicity. With respect to individual genes, AJ had a higher prevalence of pathogenic BRCA1 alterations (AJ 3.3% vs CA 0.8% vs AA 1.7%, p = 0.0034) and CHEK2 alterations (AJ 4.3% vs CA 2.8% vs AA 0.4%, p = 0.02). There were no significant differences in the prevalence of individual or specific classes of GVs between those with or without a self-reported FH of prostate or breast/ovarian cancers. There was also no association between prevalence of HR genes and age at germline testing (p = 0.40). Conclusions: This national study found that the overall prevalence of pathogenic GVs in MMR and HR genes do not differ by race, ethnicity, or age at the time of testing, and suggests that all men with advanced prostate cancer should be offered germline testing.

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