Hereditary Cancer: Example of a Public Health Approach to Ensure Population Health Benefits of Genetic Medicine

Cragun, Deborah; Lewis, Courtney; Camperlengo, Lucia; Pal, Tuya

doi:10.3390/healthcare4010006

Cited by 8 publications

(8 citation statements)

References 22 publications

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“…Through ICARE enrollment, participants are consented and asked to complete a baseline questionnaire and an authorization for the release of medical records to obtain relevant genetics records (ie, genetic test reports and pedigrees). ICARE participants are recruited through various means, including: 1) referrals from health care providers who have partnered with ICARE at various clinical centers across the United States and internationally; 2) directly online through the registry website (http://inheritedcancer.net); and 3) through local and national outreach activities . Greater than 3000 participants currently are enrolled in ICARE, of which nearly two‐thirds have a P/LP variant in an inherited cancer predisposing gene.…”

Section: Methodsmentioning

confidence: 99%

“…ICARE participants are recruited through various means, including: 1) referrals from health care providers who have partnered with ICARE at various clinical centers across the United States and internationally; 2) directly online through the registry website (http://inher itedc ancer.net); and 3) through local and national outreach activities. [16][17][18] Greater than 3000 participants currently are enrolled in ICARE, of which nearly two-thirds have a P/LP variant in an inherited cancer predisposing gene.…”

Section: Methodsmentioning

confidence: 99%

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Breast cancer screening implications of risk modeling among female relatives of ATM and CHEK2 carriers

Weidner

Liggin

Zuniga

et al. 2020

Cancer

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Background With the increasing use of multigene panel tests, pathogenic and likely pathogenic (P/LP) variants are identified more frequently in the moderate‐penetrance breast cancer genes ATM and CHEK2. Lifetime breast cancer risk among women with P/LP variants in these genes generally exceeds 20%, meeting the threshold at which high‐risk breast cancer screening through breast magnetic resonance imaging (MRI) is recommended. Methods Among a registry‐based sample of 56 ATM and 69 CHEK2 carriers, the authors sought to determine the percentage of relatives in whom a P/LP variant would impact breast cancer surveillance. Lifetime breast cancer risks for unaffected, female first‐degree and second‐degree relatives were estimated using the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA). Results Among first‐degree relatives of ATM and CHEK2 carriers, only 22.6% and 14.9%, respectively, were found to have lifetime breast cancer risks of ≥20% based on family cancer history alone; however, when including the proband's P/LP variant in the model, these percentages increased significantly to 56.6% and 55.3%, respectively (P < .0001 and P < .0001, respectively). Similar increases in lifetime breast cancer risks were found among second‐degree relatives. Conclusions The results of the current study suggest that the majority of female first‐degree and second‐degree relatives of ATM and CHEK2 carriers do not qualify for breast MRI based on family cancer history alone. Therefore, testing for these genes, as well as awareness of positive moderate‐penetrance breast cancer gene results in the family, may impact MRI eligibility. These findings highlight the potential usefulness of and need for breast cancer risk models that incorporate moderate‐penetrance gene positivity to inform screening recommendations among at‐risk family members.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Breast cancer screening implications of risk modeling among female relatives of ATM and CHEK2 carriers

Weidner

Liggin

Zuniga

et al. 2020

Cancer

Self Cite

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“…There is evidence in regard to inherited genetic testing that genetics‐trained doctors and genetic counselors with a master's degree provide more appropriate medical care and improve access to testing 135 . Although there has been a push with more genetic testing being ordered by other physicians and APPs, the role of staff with such medical expertise should not be diminished 135 . Improving reimbursement for genetic counseling appointments and ensuring adequate training programs to produce expert providers is important as well 135 .…”

Section: What Makes Molecular Pathology Susceptible To Unjust Distrib...mentioning

confidence: 99%

Toward a More Just System of Care in Molecular Pathology

et al. 2022

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r American health care policy must be critically assessed to establish the role it plays in sustaining and alleviating the health disparities that currently exist in molecular genetic testing.r It is critical to understand the economic and sociocultural influences that drive patients to undergo or forgo molecular testing, especially in marginalized patient populations.r A multipronged solution with actions necessary from multiple stakeholders is required to reduce the cost of health care, rebalance regional disparities, encourage physician engagement, reduce data bias, and earn patients' trust. Context:The health status of a population is greatly influenced by both biological processes and external factors. For years, minority and low socioeconomic patient populations have faced worse outcomes and poorer health in the United States. Experts have worked extensively to understand the issues and find solutions to alleviate this disproportionate burden of disease. As a result, there have been some improvements and successes, but wide gaps still exist. Diagnostic molecular genetic testing and so-called personalized medicine are just now being integrated into the current American health care system. The way in which these tests are integrated can either exacerbate or reduce health disparities.

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“…Extensive reviews and studies on how germline and somatically derived variants can guide therapeutic decisions have been carried out, which highlighted the importance of genome profiling of cancer ( Jia et al, 2014 ; Ab Mutalib et al, 2017 ; Chan et al, 2019 ; Yang H. et al, 2019 ). Moreover, personal genome sequencing may become essential for diagnosing, preventing, and treating human diseases, particularly cancer ( Cragun et al, 2016 ). Patient care can also be improved by transforming genomic research into personalized medicine applications by developing new and better genomics-based diagnostic tests.…”

Section: Introductionmentioning

confidence: 99%

Whole genome sequencing of Malaysian colorectal cancer patients reveals specific druggable somatic mutations

Yunos¹,

Mutalib²,

Khoo³

et al. 2023

Front. Mol. Biosci.

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The incidences of colorectal cancer (CRC) are continuously increasing in some areas of the world, including Malaysia. In this study, we aimed to characterize the landscape of somatic mutations using the whole-genome sequencing approach and identify druggable somatic mutations specific to Malaysian patients. Whole-genome sequencing was performed on the genomic DNA obtained from 50 Malaysian CRC patients’ tissues. We discovered the top significantly mutated genes were APC, TP53, KRAS, TCF7L2 and ACVR2A. Four novel, non-synonymous variants were identified in three genes, which were KDM4E, MUC16 and POTED. At least one druggable somatic alteration was identified in 88% of our patients. Among them were two frameshift mutations in RNF43 (G156fs and P192fs) predicted to have responsive effects against the Wnt pathway inhibitor. We found that the exogenous expression of this RNF43 mutation in CRC cells resulted in increased cell proliferation and sensitivity against LGK974 drug treatment and G1 cell cycle arrest. In conclusion, this study uncovered our local CRC patients’ genomic landscape and druggable alterations. It also highlighted the role of specific RNF43 frameshift mutations, which unveil the potential of an alternative treatment targeting the Wnt/β-Catenin signalling pathway and could be beneficial, especially to Malaysian CRC patients.

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Hereditary Cancer: Example of a Public Health Approach to Ensure Population Health Benefits of Genetic Medicine

Cited by 8 publications

References 22 publications

Breast cancer screening implications of risk modeling among female relatives of ATM and CHEK2 carriers

Breast cancer screening implications of risk modeling among female relatives of ATM and CHEK2 carriers

Toward a More Just System of Care in Molecular Pathology

Whole genome sequencing of Malaysian colorectal cancer patients reveals specific druggable somatic mutations

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