Role of Polygenic Risk Score in Cancer Precision Medicine of Non-European Populations: A Systematic Review

Ribeiro, Howard Lopes; Novaes, Lázaro Antônio Campanha; Datorre, José Guilherme; Moreno, Daniel Antunes; Reis, Rui Manuel

doi:10.3390/curroncol29080436

Cited by 3 publications

(2 citation statements)

References 75 publications

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“…Despite recurrent germline TP53 mutations, no other frequently occurring variants have been reported in international studies ( Cornelius et al 2017 ; Kline et al 2017 ; Taher et al 2019 ; Thomas et al 2021 ; Zhang et al 2021 ). Furthermore, the lack of representation of ancestrally diverse populations in genomic studies, especially admixed populations like the Brazilian, highlights the need for local and global initiatives to bridge this knowledge gap ( Fatumo et al 2022 ; Junior et al 2022 ). Such initiatives are crucial to identify novel variants or genetic profiles that may impact disease outcomes, or therapy decisions, ultimately improving health care for underrepresented populations ( Sirugo et al 2019 ; de Almeida et al 2022 ; Fatumo et al 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Genomic profile of two Brazilian choroid plexus tumors by whole-exome sequencing

Garcia

Evangelista

Mançano

et al. 2023

Cold Spring Harb Mol Case Stud

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Choroid plexus tumors (CPTs) are rare intracranial neoplasms, representing <1% of all brain tumors, yet they represent 20% of first-year pediatric brain tumors. Although these tumors have been linked toTP53germline mutations in the context of Li–Fraumeni syndrome, their somatic driver alterations remain poorly understood. In this study, we report two cases of lateral ventricle tumors: 3-yr-old male diagnosed with an atypical choroid plexus papilloma (aCPP), and a 6-mo-old female diagnosed with a choroid plexus carcinoma (CPC). We performed whole-exome sequencing of paired blood and tumor tissue in both patients, categorized somatic variants, and determined copy-number alterations. Our analysis revealed a tier II variant (Association for Molecular Pathology [AMP] criteria) inBRD1,aH3andTP53acetylation agent, in the aCPP. In addition, we detected copy-number gains on Chromosomes 12, 18, and 20 and copy-number losses on Chromosomes 13q and 22q (BRD1locus) in this tumor. The CPC tumor had only a pathogenic germlineTP53variant, based on American College of Medical Genetics (ACMG) criteria, with a clinical and familiar history of Li–Fraumeni syndrome. The CPC patient presented loss of heterozygosity (LoH) ofTP53loci and hyperdiploid genome. Both tumors were microsatellite-stable. This is the first study performing whole-exome sequencing in Brazilian choroid plexus tumors, and in line with the literature, we corroborate the absence of recurrent somatic mutations in these tumors. Further studies with larger sample sizes are necessary to confirm our findings and better understand the underlying biology of these tumors.

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Section: Discussionmentioning

confidence: 99%

Genomic profile of two Brazilian choroid plexus tumors by whole-exome sequencing

Garcia

Evangelista

Mançano

et al. 2023

Cold Spring Harb Mol Case Stud

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“…The importance of PRS in cancer genetics for estimating genetic risk and enabling precision medicine has been highlighted. 9 Polygenic risk score-based genetic screening of patients with CRC could yield more accurate results than the current guidelines. 10 Moreover, applying the concept of PRS to CRC revealed that the cumulative burden of CRC-associated common genetic variants is more strongly associated with early-onset CRC compared with late-onset CRC.…”

Section: Introductionmentioning

confidence: 97%

Novel genetic loci and functional properties of immune-related genes for colorectal cancer survival in Korea

Yun,

Yang,

Yang

et al. 2024

Preprint

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One major topic in colorectal cancer (CRC) research is the role of immune cells against cancer cells. The association of single-nucleotide polymorphisms (SNPs) and polygenic risk scores (PRS) with CRC was examined and their functional properties were identified using a gene-gene interaction network. 960 CRC patients at Seoul National University Hospital (SNUH, discovery) and 6,627 CRC patients at Chonnam National University Hospital (CNNUH, replication) were enrolled. SNPs were genotyped using the Korean Biobank Array. 2,729 immune-related genes were selected from the Ensembl, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes, and 37,398 SNPs were mapped. PRS were categorized into tertiles. Cox proportional hazard models were fitted for overall survival (OS) and progression-free survival (PFS). A gene-gene interaction network was analyzed. Among CRC patients from SNUH, 154 (16.0%) died, while 245 (25.5%) had progression. In CNNUH, 3,537 (53.4%) died. For OS, the most significant association was observed for rs117322760 (8q23.1, PKHD1L1, hazard ratio (HR) = 4.58, p-value = 1.40 × 10-6). For PFS, it was observed in rs143531681 (7q36.1, NOS3, HR = 4.67, p-value = 9.72 × 10-8). For PRS, the highest tertile group showed an increased risk for OS (HR = 59.58, p-value = 9.20 × 10-48) and PFS (HR = 9.81, p-value = 1.69 × 10-23). Significant interactions were observed between PIK3R2 and PIK3CA for OS and ALOX5 and COTL1 for PFS. This study presented novel genetic variants associated with OS and PFS in CRC patients, and notable findings from the analysis of PRS and the gene-gene interaction.

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Utility of polygenic scores across diverse diseases in a hospital cohort for predictive modeling

Sun,

Wang,

Liu

et al. 2024

Nat Commun

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Polygenic scores estimate genetic susceptibility to diseases. We systematically calculated polygenic scores across 457 phenotypes using genotyping array data from China Medical University Hospital. Logistic regression models assessed polygenic scores’ ability to predict disease traits. The polygenic score model with the highest accuracy, based on maximal area under the receiver operating characteristic curve (AUC), is provided on the GeneAnaBase website of the hospital. Our findings indicate 49 phenotypes with AUC greater than 0.6, predominantly linked to endocrine and metabolic diseases. Notably, hyperplasia of the prostate exhibited the highest disease prediction ability (P value = 1.01 × 10−19, AUC = 0.874), highlighting the potential of these polygenic scores in preventive medicine and diagnosis. This study offers a comprehensive evaluation of polygenic scores performance across diverse human traits, identifying promising applications for precision medicine and personalized healthcare, thereby inspiring further research and development in this field.

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Role of Polygenic Risk Score in Cancer Precision Medicine of Non-European Populations: A Systematic Review

Cited by 3 publications

References 75 publications

Genomic profile of two Brazilian choroid plexus tumors by whole-exome sequencing

Genomic profile of two Brazilian choroid plexus tumors by whole-exome sequencing

Novel genetic loci and functional properties of immune-related genes for colorectal cancer survival in Korea

Utility of polygenic scores across diverse diseases in a hospital cohort for predictive modeling

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