Hereditary Cancer Gene Variants in Hispanic Men with a Personal or Family History of Prostate Cancer

2022 ◽  
Author(s):  
Chethan Ramamurthy ◽  
Eric W. Stutz ◽  
Martin Goros ◽  
Jonathan Gelfond ◽  
Teresa L. Johnson-Pais ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
Hereditary Cancer ◽  
Gene Variants ◽  
Cancer Gene ◽  
Hispanic Men ◽  
History Of

Inherited germline mutations in men with prostate cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16564-e16564
Author(s):  
Robert Reid ◽  
Marcie DiGiovanni ◽  
Ryan Bernhisel ◽  
Krystal Brown ◽  
Jennifer Saam ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Genetic Testing ◽  
Family History ◽  
Hereditary Cancer ◽  
Clinical Information ◽  
Nccn Guidelines ◽  
Commercial Laboratory ◽  
Pathogenic Variants ◽  
Age Of Diagnosis ◽  
History Of

e16564 Background: Recent studies have demonstrated a high prevalence of pathogenic variants (PVs) in genes that confer hereditary cancer risk among men with metastatic prostate cancer (PC); however, PC does not currently receive attention as an indication for genetic testing. We assessed the clinical features of men with PC who received clinical testing as well as the distribution of PVs identified. Methods: A commercial laboratory database was queried to identify men with PC who underwent testing with a multi-gene hereditary cancer panel from September 2013–September 2016. Clinical information was obtained from provider-completed test request forms. Individuals with PC only were evaluated separately from those who had ≥1 additional malignancy. Personal/family history was evaluated relative to the 2013 NCCN guidelines for hereditary breast and ovarian cancer (HBOC) testing. Results: Overall, 700 men with a personal history of PC were identified: 384 (54.9%) with only PC and 316 (45.1%) with PC and ≥1 additional malignancy. The most common additional malignancies were colorectal (115) and breast cancer (105). The median age of diagnosis in men with only PC was 57.5, which is younger than tested men who had an additional malignancy (62) and the SEER data (2009-2013) for all men with PC (66). HBOC testing criteria were met by 75.9% of men, including 44 (6.3%) who met based only on a personal/family history of PC and 202 (28.9%) who met in part due to a personal/family history of PC. PVs were identified in 14.0% of all men: 11.5% of men with PC only and 17.1% of men with PC and a second malignancy (see Table). Conclusions: PC patients selected for genetic testing here were younger than men diagnosed with PC from the general population (SEER), and almost half had a diagnosis of an additional malignancy. They also have a high positive mutation rate across a broad spectrum of genes. [Table: see text]

Inherited germline mutations in men with prostate cancer.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 357-357
Author(s):  
Robert Reid ◽  
Marcie DiGiovanni ◽  
Ryan Bernhisel ◽  
Krystal Brown ◽  
Jennifer Saam ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Genetic Testing ◽  
Family History ◽  
Hereditary Cancer ◽  
Clinical Information ◽  
Nccn Guidelines ◽  
Pathogenic Variants ◽  
Seer Data ◽  
Age Of Diagnosis ◽  
History Of

357 Background: Recent studies have demonstrated a high prevalence of pathogenic variants (PVs) in genes that confer hereditary cancer risk among men with metastatic prostate cancer (PC); however, PC does not currently receive attention as an indication for genetic testing. We assessed the clinical features of men with PC who received clinical testing as well as the distribution of PVs identified. Methods: Men with PC who underwent testing with a multi-gene hereditary cancer panel (Myriad Genetic Laboratories) from September 2013–September 2017 were included. Clinical information was obtained from provider-completed test request forms. Individuals with PC only were evaluated separately from those who had ≥1 additional malignancy. Personal/family history was evaluated relative to the 2013 NCCN guidelines for hereditary breast and ovarian cancer (HBOC) testing. Results: Overall, 1004 men with a personal history of PC were identified: 606 (60.4%) with only PC and 398 (39.6%) with PC and ≥1 additional malignancy. The most common additional malignancies were breast (136) and colorectal cancer (134). The median age of diagnosis in men with only PC was 59, which is younger than tested men who had an additional malignancy (63) and the SEER data (2009-2013) for all men with PC (66). HBOC testing criteria were met by 78.0% of men, including 68 (6.8%) who met based only on a personal/family history of PC and 330 (32.9%) who met in part due to a personal/family history of PC. PVs were identified in 12.9% of all men: 11.2% of men with PC only and 15.4% of men with PC and a second malignancy (Table). Conclusions: PC patients selected for genetic testing here were younger than men diagnosed with PC from the general population (SEER), and about a third had a diagnosis of an additional malignancy. They also have a high positive mutation rate across a broad spectrum of genes. [Table: see text]

The impact of a positive family history on clinical and pathologic outcomes of active surveillance for prostate cancer.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 225-225
Author(s):  
Adam Schneider ◽  
Nicholas Bowler ◽  
Ryan Fogg ◽  
Joon Yau Leong ◽  
Andrew Gusev ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
Hereditary Cancer ◽  
Positive Family History ◽  
Hereditary Cancer Syndrome ◽  
Strong Family History ◽  
Cancer Syndrome ◽  
Increased Risk ◽  
History Of ◽  
The Impact

225 Background: Active surveillance (AS) is the preferred management strategy for men with low-risk prostate cancer. However, approximately one in three men on AS experience progression of disease leading to treatment within 5 years, highlighting an urgent unmet need to reliably distinguish indolent from aggressive prostate cancer and improve patient selection criteria for AS. Germline genetic testing for DNA repair gene mutations is now recommended for patients with newly diagnosed prostate cancer and a strong family history of prostate cancer or BRCA1/2-related cancers, as such mutations have been associated with more aggressive forms of the disease. Here, we investigated the impact of family history on AS outcomes, under the hypothesis that men at high genetic risk for prostate cancer are at greater risk for progression to treatment on AS. Methods: We retrospectively reviewed detailed family history data of 958 patients from our institutional database of men enrolled in AS between 1997-2019. Data on family history of prostate cancer and hereditary cancer syndrome ( BRCA1/2-related prostate, breast, ovarian and/or pancreatic cancers) were collected and integrated into a composite family history score incorporating the number of relatives with each cancer weighted by degree of relatedness. A strong family history was defined as a composite score representing > 1 first-degree relative equivalent. The primary outcome was biopsy progression and secondary outcomes were adverse pathologic features at prostatectomy and biochemical recurrence. Statistical analysis was conducted using the Kaplan-Meier method and Cox proportional hazards regression. Results: In univariate analysis, a strong family history suggestive of a hereditary cancer syndrome (HR 1.37 [1.03-1.90], P = 0.033) was associated with a significant increased risk of biopsy progression; however, any family history of prostate cancer (HR 1.10 [0.89-1.35], P = 0.38) and a strong family history of prostate cancer (HR 1.35 [0.92-1.98], P = 0.13) were not significant. In multivariate analysis, a strong family history suggestive of a hereditary cancer syndrome remained a statistically significant predictor of biopsy progression (HR 1.42 [1.03-1.96], P = 0.03), after adjusting for age, percent core involvement on initial biopsy and PSA density. No significant association was found between family history and adverse features on surgical pathology or biochemical recurrence. Conclusions: A positive family history suggestive of a hereditary cancer syndrome is associated with an increased risk of biopsy progression on AS and is an independent predictor of biopsy progression. Men with such a family history may still be safely offered AS but should be counseled about the higher risk of progression. Further work to investigate the underlying genetic factors responsible for this increased risk is warranted.

The PROFILE study. Targeted screening using germline genetics in men with a family history of prostate cancer

2021 ◽  
Vol 79 ◽  
pp. S1395
Author(s):  
H. Ni Raghallaigh ◽  
M.N. Brook ◽  
E.J. Saunders ◽  
P. Kumar ◽  
S. Hazell ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
Targeted Screening ◽  
History Of ◽  
Profile Study

T2044 Family History of Pancreas, Breast, Colon, Bladder, and Prostate Cancer in Patients with Pancreas Cancer Supports a Syndromic Predisposition

2008 ◽  
Vol 134 (4) ◽  
pp. A-607
Author(s):  
Aimee L. Lucas ◽  
Aliye Z. Bill ◽  
Caroline Hwang ◽  
Elizabeth Verna ◽  
Nicole Goetz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
Pancreas Cancer ◽  
History Of

scholarly journals Multi-cohort modeling strategies for scalable globally accessible prostate cancer risk tools

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Johanna Tolksdorf ◽  
Michael W. Kattan ◽  
Stephen A. Boorjian ◽  
Stephen J. Freedland ◽  
Karim Saba ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Factors ◽  
Family History ◽  
Cancer Risk ◽  
Risk Prediction ◽  
Prostate Biopsy ◽  
Prostate Cancer Risk ◽  
High Grade ◽  
Prediction Tools ◽  
History Of

Abstract Background Online clinical risk prediction tools built on data from multiple cohorts are increasingly being utilized for contemporary doctor-patient decision-making and validation. This report outlines a comprehensive data science strategy for building such tools with application to the Prostate Biopsy Collaborative Group prostate cancer risk prediction tool. Methods We created models for high-grade prostate cancer risk using six established risk factors. The data comprised 8492 prostate biopsies collected from ten institutions, 2 in Europe and 8 across North America. We calculated area under the receiver operating characteristic curve (AUC) for discrimination, the Hosmer-Lemeshow test statistic (HLS) for calibration and the clinical net benefit at risk threshold 15%. We implemented several internal cross-validation schemes to assess the influence of modeling method and individual cohort on validation performance. Results High-grade disease prevalence ranged from 18% in Zurich (1863 biopsies) to 39% in UT Health San Antonio (899 biopsies). Visualization revealed outliers in terms of risk factors, including San Juan VA (51% abnormal digital rectal exam), Durham VA (63% African American), and Zurich (2.8% family history). Exclusion of any cohort did not significantly affect the AUC or HLS, nor did the choice of prediction model (pooled, random-effects, meta-analysis). Excluding the lowest-prevalence Zurich cohort from training sets did not statistically significantly change the validation metrics for any of the individual cohorts, except for Sunnybrook, where the effect on the AUC was minimal. Therefore the final multivariable logistic model was built by pooling the data from all cohorts using logistic regression. Higher prostate-specific antigen and age, abnormal digital rectal exam, African ancestry and a family history of prostate cancer increased risk of high-grade prostate cancer, while a history of a prior negative prostate biopsy decreased risk (all p-values < 0.004). Conclusions We have outlined a multi-cohort model-building internal validation strategy for developing globally accessible and scalable risk prediction tools.

Family history of prostate cancer in patients with localized prostate cancer: an independent predictor of treatment outcome.

1997 ◽  
Vol 15 (4) ◽  
pp. 1478-1480 ◽  
Author(s):  
P A Kupelian ◽  
V A Kupelian ◽  
J S Witte ◽  
R Macklis ◽  
E A Klein
Keyword(s):  
Prostate Cancer ◽  
Treatment Outcome ◽  
Family History ◽  
Treatment Modality ◽  
Proportional Hazards ◽  
Positive Family History ◽  
Specific Antigen ◽  
Tumor Stage ◽  
Degree Relative ◽  
History Of

PURPOSE To determine if familial prostate cancer patients have a less favorable prognosis than patients with sporadic prostate cancer after treatment for localized disease with either radiotherapy (RT) or radical prostatectomy (RP). PATIENTS AND METHODS One thousand thirty-eight patients treated with either RT (n = 583) or RP (n = 455) were included in this analysis. These patients were noted as having a positive family history if they confirmed the diagnosis of prostate cancer in a first-degree relative. The outcome of interest was biochemical relapse-free survival (bRFS). We used proportional hazards to analyze the effect of the presence of family history and other potential confounding variables (ie, age, treatment modality, stage, biopsy Gleason sum [GS], and initial prostate-specific antigen [iPSA] levels) on treatment outcome. RESULTS Eleven percent of all patients had a positive family history. The 5-year bRFS rates for patients with negative and positive family histories were 52% and 29%, respectively (P < .001). The potential confounders with bRFS rates were iPSA levels, biopsy GS, and clinical tumor stage; treatment modality and age did not appear to be associated with outcome. After adjusting for potential confounders, family history of prostate cancer remained strongly associated with biochemical failure. CONCLUSION This is the first study to demonstrate that the presence of a family history of prostate cancer correlates with treatment outcome in a large unselected series of patients. Our findings suggest that familial prostate cancer may have a more aggressive course than nonfamilial prostate cancer, and that clinical and/or pathologic parameters may not adequately predict this course.

scholarly journals Prostate cancer screening characteristics in men with BRCA1/2 mutations attending a high-risk prevention clinic

2014 ◽  
Vol 8 (11-12) ◽  
pp. 783 ◽  
Author(s):  
Richard Walker ◽  
Alyssa Louis ◽  
Alejandro Berlin ◽  
Sheri Horsburgh ◽  
Robert G. Bristow ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
High Risk ◽  
Prostate Cancer Screening ◽  
Brca2 Mutation ◽  
Aggressive Disease ◽  
Mutation Carriers ◽  
The Family ◽  
History Of ◽  
Prevention Clinic

Introduction: The prostate-specific antigen (PSA) era and resultant early detection of prostate cancer has presented clinicians with the challenge of distinguishing indolent from aggressive tumours. Mutations in the BRCA1/2 genes have been associated with prostate cancer risk and prognosis. We describe the prostate cancer screening characteristics of BRCA1/2 mutation carriers, who may be classified as genetically-defined high risk, as compared to another high-risk cohort of men with a family history of prostate cancer to evaluate the utility of a targeted screening approach for these men.Methods: We reviewed patient demographics, clinical screening characteristics, pathological features, and treatment outcomes between a group of BRCA1 or BRCA2 mutation carriers and age-matched men with a family history of prostate cancer followed at our institutional Prostate Cancer Prevention Clinic from 1995 to 2012.Results: Screening characteristics were similar between the mutation carriers (n = 53) and the family history group (n = 53). Some cancers would be missed in both groups by using a PSA cut-off of >4 ug/L. While cancer detection was higher in the family history group (21% vs. 15%), the mutation carrier group was more likely to have intermediate- or high-risk disease (88% vs. 36%). BRCA2 mutation carriers were more likely to have aggressive disease, biological recurrence, and distant metastasis.Conclusions: In our cohort, regular screening appears justified for detecting prostate cancer in BRCA1 and BRCA2 carriers and other high-risk populations. Lowering PSA cut-offs and defining monitoring of PSA velocity as part of the screening protocol may be useful. BRCA2 is associated with more aggressive disease, while the outcome for BRCA1 mutation carriers requires further study. Large multinational studies will be important to define screening techniques for this unique high-risk population.

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