Dataset Information

Recent Insights on Genetic Testing in Primary Prostate Cancer.

ABSTRACT: Prostate cancer (PCa) is one of the most common cancers in developed countries. The results of large trials indicate that the proportion of PCa attributable to hereditary factors is as high as 15%, highlighting the importance of genetic testing. Despite improved understanding of the prevalence of pathogenic variants among men with PCa, it remains unclear which men will most benefit from genetic testing. In this review, we summarize recent evidence on genetic testing in primary PCa and its impact on routine clinical practice. We outline current guideline recommendations on genetic testing, most importantly, for mutations in BRCA1/2, MMR, CHEK2, PALB2, and HOXB13 genes, as well as various single nucleotide polymorphisms associated with an increased risk of developing PCa. The implementation of genetic testing in clinical practice, especially in young patients with aggressive tumors or those with positive family history, represents a new challenge for the coming years and will identify men with pathogenic variants who may benefit from early screening/intervention and specific therapeutic options.

SUBMITTER: Kafka M

PROVIDER: S-EPMC8249272 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Recent Insights on Genetic Testing in Primary Prostate Cancer.

Kafka Mona M Surcel Cristian C Heidegger Isabel I

Molecular diagnosis & therapy 20210612 4

Prostate cancer (PCa) is one of the most common cancers in developed countries. The results of large trials indicate that the proportion of PCa attributable to hereditary factors is as high as 15%, highlighting the importance of genetic testing. Despite improved understanding of the prevalence of pathogenic variants among men with PCa, it remains unclear which men will most benefit from genetic testing. In this review, we summarize recent evidence on genetic testing in primary PCa and its impact ...[more]

PMID: 34118026

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Project description:BackgroundGenetic testing, to identify pathogenic or likely pathogenic variants in prostate cancer, is valuable in guiding treatment decisions for men with prostate cancer and to inform cancer prevention and early detection options for their immediate blood relatives. There are various guidelines and consensus statements for genetic testing in prostate cancer. Our aim is to review genetic testing recommendations across current guidelines and consensus statements and the level of evidence supporting those recommendations.MethodsA scoping review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping review (PRISMA-ScR) guidelines. Electronic database searches and manual searches of grey literature, including websites of key organisations were conducted. Using the Population, Concept, Context (PCC) framework, this scoping review included: men with prostate cancer or men at high risk of prostate cancer and their biological families; existing guidelines and consensus statements with supporting evidence for genetic testing of men with prostate cancer from any geographical location worldwide.ResultsOf the 660 citations identified, 23 guidelines and consensus statements met the inclusion criteria for the scoping review. Based on different levels of evidence about who should be tested and how, a diverse range of recommendations were identified. There was general consensus among the guidelines and consensus statements that men with metastatic disease be offered genetic testing; however, there was less consensus in relation to genetic testing in localised prostate cancer. While there was some consensus in relation to which genes to test, recommendations varied regarding who to test, testing methods and implementation.ConclusionWhile genetic testing in prostate cancer is routinely recommended and numerous guidelines exist, there is still considerable lack of consensus regarding who should be tested and how they should be tested. Further evidence is needed to inform value-based genetic testing strategies for implementation in practice.

Project description:Prostate cancer (PCa) has a high propensity for metastasis to bone. Despite the availability of multiple treatment options for relief of PCa-induced bone pain (PCIBP), satisfactory relief of intractable pain in patients with advanced bony metastases is challenging for the clinicians because currently available analgesic drugs are often limited by poor efficacy and/or dose-limiting side effects. Rodent models developed in the past decade show that the pathobiology of PCIBP comprises elements of inflammatory, neuropathic and ischemic pain arising from ectopic sprouting and sensitization of sensory nerve fibres within PCa-invaded bones. In addition, at the cellular level, PCIBP is underpinned by dynamic cross talk between metastatic PCa cells, cellular components of the bone matrix, factors associated with the bone microenvironment as well as peripheral components of the somatosensory system. These insights are aligned with the clinical management of PCIBP involving use of a multimodal treatment approach comprising analgesic agents (opioids, NSAIDs), radiotherapy, radioisotopes, cancer chemotherapy agents and bisphosphonates. However, a major drawback of most rodent models of PCIBP is their short-term applicability due to ethical concerns. Thus, it has been difficult to gain insight into the mal(adaptive) neuroplastic changes occurring at multiple levels of the somatosensory system that likely contribute to intractable pain at the advanced stages of metastatic disease. Specifically, the functional responsiveness of noxious circuitry as well as the neurochemical signature of a broad array of pro-hyperalgesic mediators in the dorsal root ganglia and spinal cord of rodent models of PCIBP is relatively poorly characterized. Hence, recent work from our laboratory to develop a protocol for an optimized rat model of PCIBP will enable these knowledge gaps to be addressed as well as identification of novel targets for drug discovery programs aimed at producing new analgesics for the improved relief of intractable PCIBP.

Project description:PurposeGermline mutations in DNA repair genes are present in approximately 10% of men with metastatic prostate cancer (mPC), and guidelines recommend genetic germline testing. Notable barriers exist, including access to genetic counseling, insurance coverage, and out-of-pocket costs. The GENTleMEN study was designed to determine the feasibility of an Internet-based, patient-driven germline genetic testing approach for men with mPC.Patients and methodsIn this prospective cohort study, men with mPC provided informed consent via an Internet-based platform and completed a questionnaire including demographics and family cancer history. Supporting medical data were also collected. Genetic testing was performed using the Color Genomics 30-gene targeted panel of cancer predisposition genes on a mailed saliva sample. Men whose test results identified a germline pathogenic or likely pathogenic variant received results by phone or telehealth genetic counseling; other participants received results by email with an option for phone-based or telehealth genetic counseling.ResultsAs of August 18, 2021, 816 eligible men were consented, of whom 68% (551) completed genetic testing, and 8.7% (48 of 551) were found to carry a pathogenic or likely pathogenic variant in a germline DNA repair gene: CHEK2 (17), BRCA2 (15), ATM (6), NBN1 (3), BRCA1 (2), PALB2 (2), PMS2 (2), and MSH6 (1). Participants were more likely to complete the testing process if they were non-Hispanic White, married, highly educated, or from a higher-income bracket.ConclusionHere, we show the feasibility of delivering germline (inherited) genetic testing by a voluntary, patient-driven, Internet-based platform to men with mPC. Preliminary results show rates of germline DNA repair mutations, consistent with other cohorts. Although feasible for some, reduced steps for participation, more dedicated diverse outreach and participant support, and identification and addressing of additional barriers is needed to ensure equitable access and optimization.

Dataset Information

Recent Insights on Genetic Testing in Primary Prostate Cancer.

Publications

Recent Insights on Genetic Testing in Primary Prostate Cancer.

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