scholarly journals Genetic predisposition to prostate cancer: an update

2021 ◽  
Author(s):  
Holly Ni Raghallaigh ◽  
Rosalind Eeles

AbstractImprovements in DNA sequencing technology and discoveries made by large scale genome-wide association studies have led to enormous insight into the role of genetic variation in prostate cancer risk. High-risk prostate cancer risk predisposition genes exist in addition to common germline variants conferring low-moderate risk, which together account for over a third of familial prostate cancer risk. Identifying men with additional risk factors such as genetic variants or a positive family history is of clinical importance, as men with such risk factors have a higher incidence of prostate cancer with some evidence to suggest diagnosis at a younger age and poorer outcomes. The medical community remains in disagreement on the benefits of a population prostate cancer screening programme reliant on PSA testing. A reduction in mortality has been demonstrated in many studies, but at the cost of significant amounts of overdiagnosis and overtreatment. Developing targeted screening strategies for high-risk men is currently the subject of investigation in a number of prospective studies. At present, approximately 38% of the familial risk of PrCa can be explained based on published SNPs, with men in the top 1% of the risk profile having a 5.71-fold increase in risk of developing cancer compared with controls. With approximately 170 prostate cancer susceptibility loci now identified in European populations, there is scope to explore the clinical utility of genetic testing and genetic-risk scores in prostate cancer screening and risk stratification, with such data in non-European populations eagerly awaited. This review will focus on both the rare and common germline genetic variation involved in hereditary and familial prostate cancer, and discuss ongoing research in exploring the role of targeted screening in this high-risk group of men.

2016 ◽  
Vol 23 (14) ◽  
pp. 1800-1809 ◽  
Author(s):  
Pagona Roussi ◽  
Suzanne M Miller ◽  
Veda N Giri ◽  
Elias Obeid ◽  
Kuang-Yi Wen ◽  
...  

Despite conflicting guidelines, a significant subset of high-risk men decide to undergo routine prostate cancer screening. Yet, there is a scarcity of available programs, and no studies evaluating interventions to support men in dealing with the psychosocial impact of screening. In this study, one of the first to explore the responses of high-risk men enrolling in a Prostate Cancer Risk Assessment Program ( N = 128), patients underwent a prostate cancer risk counseling visit immediately followed by either a cognitive–affective preparation session designed to help them process the information they received or a general health education session. All men in this self-selected sample chose to participate in prostate cancer screening. Men were assessed 3 weeks and 6 months post-counseling. The impact of the enhanced counseling condition on knowledge, perceived risk, expectancies, and intrusive ideation was a function of racial and coping style group. Implications for tailored interventions to maximize preparedness for risk and screening counseling are discussed.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Victoria Hale ◽  
Maren Weischer ◽  
Jong Y. Park

Although the causes of prostate cancer are largely unknown, previous studies support the role of genetic factors in the development of prostate cancer.CHEK2plays a critical role in DNA replication by responding to double-stranded breaks. In this review, we provide an overview of the current knowledge of the role of a genetic variant, 1100delC, ofCHEK2on prostate cancer risk and discuss the implication for potential translation of this knowledge into clinical practice. Currently, twelve articles that discussedCHEK2∗1100delC and its association with prostate cancer were identified. Of the twelve prostate cancer studies, five studies had independent data to draw conclusive evidence from. The pooled results of OR and 95% CI were 1.98 (1.23–3.18) for unselected cases and 3.39 (1.78–6.47) for familial cases, indicating thatCHEK2∗1100delC mutation is associated with increased risk of prostate cancer. Screening for CHEK2∗1100delC should be considered in men with a familial history of prostate cancer.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Johanna Tolksdorf ◽  
Michael W. Kattan ◽  
Stephen A. Boorjian ◽  
Stephen J. Freedland ◽  
Karim Saba ◽  
...  

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.


2003 ◽  
Vol 2 (1) ◽  
pp. 26
Author(s):  
C. Auzanneau ◽  
J. Irani ◽  
L. Dahmani ◽  
F. Ouaki ◽  
C. Pirès ◽  
...  

2021 ◽  
Author(s):  
Antonio Bandala-Jacques ◽  
Kevin Daniel Castellanos Esquivel ◽  
Fernanda Pérez-Hurtado ◽  
Cristobal Hernández-Silva ◽  
Nancy Reynoso-Noverón

BACKGROUND Screening for prostate cancer has long been a debated, complex topic. The use of risk calculators for prostate cancer is recommended for determining patients’ individual risk of cancer and the subsequent need for a prostate biopsy. These tools could lead to a better discrimination of patients in need of invasive diagnostic procedures and for optimized allocation of healthcare resources OBJECTIVE To systematically review available literature on current prostate cancer risk calculators’ performance in healthy population, by comparing the impact factor of individual items on different cohorts, and the models’ overall performance. METHODS We performed a systematic review of available prostate cancer risk calculators targeted at healthy population. We included studies published from January 2000 to March 2021 in English, Spanish, French, Portuguese or German. Two reviewers independently decided for or against inclusion based on abstracts. A third reviewer intervened in case of disagreements. From the selected titles, we extracted information regarding the purpose of the manuscript, the analyzed calculators, the population for which it was calibrated, the included risk factors, and the model’s overall accuracy. RESULTS We included a total of 18 calculators across 53 different manuscripts. The most commonly analyzed ones were they PCPT and ERSPC risk calculators, developed from North American and European cohorts, respectively. Both calculators provided high precision for the diagnosis of aggressive prostate cancer (AUC as high as 0.798 for PCPT and 0.91 for ERSPC). We found 9 calculators developed from scratch for specific populations, which reached diagnostic precisions as high as 0.938. The most commonly included risk factors in the calculators were age, PSA levels and digital rectal examination findings. Additional calculators included race and detailed personal and family history CONCLUSIONS Both the PCPR and the ERSPC risk calculators have been successfully adapted for cohorts other than the ones they were originally created for with no loss of diagnostic accuracy. Furthermore, designing calculators from scratch considering each population’s sociocultural differences has resulted in risk tools that can be well adapted to be valid in more patients. The best risk calculator for prostate cancer will be that which was has been calibrated for its intended population and can be easily reproduced and implemented CLINICALTRIAL CRD42021242110


2019 ◽  
Vol 28 (7) ◽  
pp. 1259-1261
Author(s):  
Anqi Wang ◽  
John R. Barber ◽  
Adrienne Tin ◽  
Angelo M. De Marzo ◽  
Anna Kottgen ◽  
...  

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