Population genomic screening of all young adults in a health-care system: a cost-effectiveness analysis

Zhang, Lei; Bao, Yining; Riaz, Moeen; Tiller, Jane; Liew, Danny; Zhuang, Xun; Amor, David J.; Huq, Aamira; Petelin, Lara; Nelson, Mark; James, Paul; Winship, Ingrid; McNeil, John J; Lacaze, Paul

doi:10.1038/s41436-019-0457-6

Cited by 80 publications

(63 citation statements)

References 37 publications

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“…Finally, healthy individuals in families with familial LC should undergo such WES tests because they may share the same fragile germline basis as the probands. This echoes a recent study that the population genomic screening of all young adults is extremely cost-effective in disease prevention and enhancing life quality [32]. Our…”

Section: Discussionsupporting

confidence: 83%

Germline Variation Networks in the PI3K/AKT Pathway Corresponding to Familial High-incidence Lung Cancer Pedigrees

Lin

Zhang²,

Zhang

et al. 2020

Preprint

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Background: There were scarcely germline variants of familial lung cancer (LC) identified. We conducted an study with whole-exome sequencing of pedigrees with familial lung cancer to analyze the potential genetic susceptibility. Methods: Probands with the highest hereditary background were identified by our large-scale epidemiological study and five ones were enrolled as a learning set. The germline SNPs (single-nucleotide polymorphisms) of other five similar probands, four healthy individuals in the formerly pedigrees and three patients with sporadic LC were used as a validation set, controlled by three healthy individuals without family history of any cancer. The network of mutated genes was generated using STRING-DB and visualized using Cytoscape. Results: Specific and shared somatic mutations and germline SNPs were not the shared cause of familial lung cancer. However, individual germline SNPs showed distinct protein-protein interaction network patterns in probands versus healthy individuals and patients with sporadic lung cancer. SNP-containing genes were enriched in the PI3K/AKT pathway. These results were validated in the validation set. Furthermore, patients with familial lung cancer were distinguished by many germline variations in the PI3K/AKT pathway by a simple SVM classification method. It is worth emphasizing that one person with many germline variations in the PI3K/AKT pathway developed lung cancer during follow-up. Conclusions: The phenomenon that the enrichments of germline SNPs in the PI3K/AKT pathway might be a major predictor of familial susceptibility to lung cancer.

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Section: Discussionsupporting

confidence: 83%

Germline Variation Networks in the PI3K/AKT Pathway Corresponding to Familial High-incidence Lung Cancer Pedigrees

Lin

Zhang²,

Zhang

et al. 2020

Preprint

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“…For breast cancer, BRCA screening in the context of high-risk populations has already been shown to be cost-effective in the USA and UK [10,55], and recent evidence has shown screening for hereditary breast and ovarian cancer genes in an unselected population to be costeffective over testing based on clinical or family history criteria [44]. In addition, a recent cost-effectiveness evaluation of early adulthood screening for BRCA1/BRCA2/MLH1/MSH2 with carrier screening for cystic fibrosis, spinal muscular atrophy and fragile X syndrome in the Australian single-payer system found this approach to be highly effective in preventing cancer deaths and highly cost-effective [56]. Polygenic risk-informed cancer screening has also been shown to be cost-effective in breast cancer [11,57], with evaluations in colorectal and prostate cancer underway.…”

Section: Programme/system Principlesmentioning

confidence: 99%

Evaluating the Integration of Genomics into Cancer Screening Programmes: Challenges and Opportunities

Briggs

Slade

2019

Curr Genet Med Rep

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Purpose of Review As the costs of genomic testing have fallen, and our understanding of genetic susceptibility to cancers has grown, there has been increasing interest in incorporating testing for cancer susceptibility genes, and polygenic risk estimates, into population cancer screening. A growing body of evidence suggests that this would be both clinically and cost-effective. In this article, we aim to explore the frameworks used to evaluate screening programmes, evaluate whether population screening for cancer susceptibility can be assessed using these standards, and consider additional issues and outcomes of importance in this context. Recent Findings There are tensions between traditional approaches of genetic testing (utilising tests with high sensitivity and specificity) and the principles of population screening (in which the screening test typically has low specificity), as well as the frameworks used to evaluate the two. Despite the existence of many screening guidelines, including consensus papers, these often do not align fully with broader considerations of genetic test evaluation. Population screening for genetic risk in cancer shifts the focus from diagnostics to prognostication and has wider implications for personal and familial health than existing screening programmes. In addition, understanding of the prevalence and penetrance of cancer susceptibility genes, required by many screening guidelines, may only be obtainable through population-level testing; prospective multidisciplinary research alongside implementation will be essential. Summary Appropriate evaluation of genetic screening for cancer risk will require modification of existing screening frameworks to incorporate additional complexity of outcomes and population values. As evidence supporting population screening for cancer susceptibility mounts, development of an appropriate evaluative framework, and expansion of public dialogue will be key to informing policy.

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“…Zhanga et al considered the impact and cost-effectiveness of offering preventive population genomic screening for BRCA1/2, MLH1/MSH2 genes, cystic brosis, spinal muscular atrophy and fragile X syndrome to all young adults (18)(19)(20)(21)(22)(23)(24)(25) years) in a single-payer health-care system in Australia, and reported that it would be highly cost-effective, but ethical issues need to be considered [17].…”

Section: Introductionmentioning

confidence: 99%

NGS based expanded carrier screening for genetic disorders in North Indian population reveals unexpected results – a pilot study.

Singh¹,

Bijarnia-Mahay²,

Ramprasad

et al. 2020

Preprint

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Background: To determine the carrier frequency and pathogenic variants of common genetic disorders in the north Indian population by using next generation sequencing (NGS).Methods: After pre-test counselling, 200 unrelated individuals (including 88 couples) were screened for pathogenic variants in 88 genes by NGS technology. The variants were classified as per American College of Medical Genetics criteria. Pathogenic and likely pathogenic variants were subjected to thorough literature-based curation in addition to the regular filters. Variants of unknown significance were not reported. Individuals were counselled explaining the implications of the results, and cascade screening was advised when necessary.Results: Of the 200 participants, 52 (26 %) were found to be carrier of one or more disorders. Twelve individuals were identified to be carriers for congenital deafness, giving a carrier frequency of one in 17 for one of the four genes tested (SLC26A4, GJB2, TMPRSS3 and TMC1 in decreasing order). Nine individuals were observed to be carriers for cystic fibrosis, with a frequency of one in 22. Three individuals were detected to be carriers for Pompe disease (frequency one in 67). None of the 88 couples screened were found to be carriers for the same disorder. The pathogenic variants observed in many disorders (such as deafness, cystic fibrosis, Pompe disease, Canavan disease, primary hyperoxaluria, junctional epidermolysis bullosa, galactosemia, medium chain acyl CoA deficiency etc.) were different from those commonly observed in the West. Conclusion: A higher carrier frequency for genetic deafness, cystic fibrosis and Pompe disease was unexpected, and contrary to the generally held view about their prevalence in Asian Indians. In spite of the small sample size, this study would suggest that population-based carrier screening panels for India would differ from those in the West, and need to be selected with due care. Testing should comprise the study of all the coding exons with its boundaries in the genes through NGS, as all the variants are not well characterized. Only study of entire coding regions in the genes will detect carriers with adequate efficiency, in order to reduce the burden of genetic disorders in India and other resource poor countries.

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Population genomic screening of all young adults in a health-care system: a cost-effectiveness analysis

Cited by 80 publications

References 37 publications

Germline Variation Networks in the PI3K/AKT Pathway Corresponding to Familial High-incidence Lung Cancer Pedigrees

Germline Variation Networks in the PI3K/AKT Pathway Corresponding to Familial High-incidence Lung Cancer Pedigrees

Evaluating the Integration of Genomics into Cancer Screening Programmes: Challenges and Opportunities

NGS based expanded carrier screening for genetic disorders in North Indian population reveals unexpected results – a pilot study.

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