Inherited risk assessment and its clinical utility for predicting prostate cancer from diagnostic prostate biopsies

Xu, Jianfeng; Resurreccion, W. Kyle; Shi, Zhuqing; Wei, Jun; Wang, Chi‐Hsiung; Zheng, S. Lilly; Hulick, Peter J.; Ross, Ashley E.; Pavlovich, Christian P.; Helfand, Brian T.; Isaacs, William B.

doi:10.1038/s41391-021-00458-6

Cited by 13 publications

(20 citation statements)

References 102 publications

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“…While the reliability of risk estimates from polygenic risk scores has consistently been demonstrated in EUR ancestry, including a large population-based cohort from the UKB and a clinical trial population REDUCE (REduction by DUtasteride of prostate Cancer Events) [18] , [26] , it has not been assessed in non-European populations. This inequality poses one of the most important ethical and scientific challenges surrounding the routine implementation of polygenic risk scores into the clinic [16] . There is a major concern that current EUR-centric polygenic risk scores may exacerbate health disparities [17] .…”

Section: Discussionmentioning

confidence: 99%

“…Despite the consistent results from large research populations, polygenic risk score testing has not been adopted by guidelines for risk stratification at the individual patient level [5] , [6] . Several outstanding challenges are generally cited [16] , including (1) a lack of supporting data from prospective studies, (2) reliability of their risk estimates, and (3) generalizability in non-European racial/ethnic populations [17] . The first challenge was recently addressed in a large PCa prospective cohort from the UKB [12] , [18] .…”

Section: Introductionmentioning

confidence: 99%

“…The latter is required for calculating an individual’s relative and lifetime risk. A lack of reliability data of polygenic risk scores in non-European populations hinders the broad implementation of polygenic risk scores in genetic testing and further exacerbates the racial/ethnic disparity in PCa screening [16] , [17] . This disparity is particularly prominent for men of AFR ancestry who are at the highest risk of developing and dying from PCa [21] .…”

Section: Introductionmentioning

confidence: 99%

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Reliability of Ancestry-specific Prostate Cancer Genetic Risk Score in Four Racial and Ethnic Populations

Shi

Zhan

Wei

et al. 2022

European Urology Open Science

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Reliability of Ancestry-specific Prostate Cancer Genetic Risk Score in Four Racial and Ethnic Populations

Shi

Zhan

Wei

et al. 2022

European Urology Open Science

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“…Clinical trials and implementation projects are underway, [10][11][12][13][14] and several commercial laboratories already offer PRS products for clinical use. [15][16][17] Most attention has focused on the potential for PRS to identify high-risk subgroups of patients for whom targeted interventions might improve health outcomes through earlier prevention, detection, or treatment; 4,10,18 the potential for PRS to identify low-risk subgroups for whom certain preventive measures might be appropriately deferred remains more theoretical. 19,20 Whereas preventive medicine is most often the domain of primary care, the successful implementation of PRS for risk stratification and prevention will depend on the clinical utility and barriers that primary care physicians (PCPs) perceive to their use.…”

Section: Introductionmentioning

confidence: 99%

“…Clinical trials and implementation projects are underway, 10–14 and several commercial laboratories already offer PRS products for clinical use. 15–17 Most attention has focused on the potential for PRS to identify high-risk subgroups of patients for whom targeted interventions might improve health outcomes through earlier prevention, detection, or treatment; 4,10,18 the potential for PRS to identify low-risk subgroups for whom certain preventive measures might be appropriately deferred remains more theoretical. 19,20…”

Section: Introductionmentioning

confidence: 99%

Benefits and barriers to implementing precision preventive care: results of a national physician survey

Vassy

Kerman

Harris

et al. 2022

Preprint

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Background: Clinical implementation of polygenic risk scores (PRS) for precision prevention depends on the utility and barriers primary care physicians (PCPs) perceive to their use. Methods: An online survey asked PCPs in a national database about the clinical utility of PRS they perceived for categories of medical decision-making and perceived benefits of and barriers to that use. Latent class analysis (LCA) was used to identify subgroups of PCPs based on response patterns. Results: Among 367 respondents (email open rate 10.8%; participation rate 96.3%; completion rate 93.1%), mean (SD) age was 54.9 (12.9) years, 137 (37.3%) were female, and mean (SD) time since medical school graduation was 27.2 (13.3) years. Respondents reported greater perceived utility for more clinical action (e.g., earlier or more intensive screening, preventive medications, or lifestyle modification) for patients with high-risk PRS than for delayed or discontinued prevention actions for low-risk patients (p<0.001). Respondents most often chose out-of-pocket costs (48%), lack of clinical guidelines (24%), and patient insurance discrimination concerns (22%) as extreme barriers to PRS implementation. LCA identified 3 subclasses of respondents. Skeptics (n=83, 22.6%) endorsed less agreement with individual clinical utilities, saw patient anxiety and insurance discrimination as significant barriers, and agreed less often that PRS could help patients make better health decisions. Learners (n=134, 36.5%) and enthusiasts (n=150, 40.9%) expressed similar levels of agreement that PRS had utility for preventive actions and that PRS could be useful for patient decision-making. Compared with enthusiasts, however, learners perceived greater barriers to the clinical use of PRS. Conclusion: PCPs generally endorsed using PRS to guide medical decision-making about preventive care, with a preference for more clinical action over less. Barriers identified suggest interventions to address the needs and concerns of PCPs along the spectrum of acceptance and uptake.

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Systematic review of reported association studies of monogenic genes and bladder cancer risk and confirmation analysis in a large population cohort

et al. 2022

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Objectives: To evaluate which of previously reported monogenic genes are associated with increased bladder cancer risk, we reviewed published papers on associations of genes and bladder cancer risk and performed a confirmation study of these genes in a large population-based cohort. Subjects and methods:A systematic review of published papers prior to June 2022 was performed first to identify all genes where germline mutations were associated with bladder cancer risk. The associations of these candidate genes with bladder cancer risk were then tested among 1695 bladder cancer cases and 186 271 controls in the UK Biobank (UKB). The robust SKAT-O, a gene-based analysis that properly controls for type I error rates due to unbalanced case-control ratio, was used for association tests adjusting for age at recruitment, gender, smoking status, and genetic background.Results: The systematic review identified nine genes that were significantly associated with bladder cancer risk in at least one study (p < 0.05), including MUTYH, MSH2, MSH6, MLH1, ATM, BRCA2, ERCC5, TGFB1 and CHEK2. When pathogenic/ likely pathogenic mutations were aggregated within each gene, the association was confirmed for three genes in the UKB at p < 0.0056 (Bonferroni correction for nine tests), including CHEK2, ATM and BRCA2, all also known to be associated with hereditary breast cancer. Suggestive evidence of association was found for two other genes, including MLH1 (p = 0.006) and MSH2 (p = 0.007), both known to be associated with Lynch syndrome. Among these five genes, the bladder cancer risks range Abrar Mian and Jun Wei contributed equally to this work.

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Inherited risk assessment and its clinical utility for predicting prostate cancer from diagnostic prostate biopsies

Cited by 13 publications

References 102 publications

Reliability of Ancestry-specific Prostate Cancer Genetic Risk Score in Four Racial and Ethnic Populations

Reliability of Ancestry-specific Prostate Cancer Genetic Risk Score in Four Racial and Ethnic Populations

Benefits and barriers to implementing precision preventive care: results of a national physician survey

Systematic review of reported association studies of monogenic genes and bladder cancer risk and confirmation analysis in a large population cohort

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