Polymorphisms and Pharmacogenomics of NQO2: The Past and the Future

Genes, Journal Year: 2024, Volume and Issue: 15(1), P. 87 - 87

Published: Jan. 10, 2024

The flavoenzyme N-ribosyldihydronicotinamide (NRH):quinone oxidoreductase 2 (NQO2) catalyzes two-electron reductions of quinones. NQO2 contributes to the metabolism biogenic and xenobiotic quinones, including a wide range antitumor drugs, with both toxifying detoxifying functions. Moreover, activity can be inhibited by several compounds, drugs phytochemicals such as flavonoids. may play important roles that go beyond quinone include regulation oxidative stress, inflammation, autophagy, implications in carcinogenesis neurodegeneration. is highly polymorphic gene allelic variants, insertions (I), deletions (D) single-nucleotide (SNP) polymorphisms located mainly promoter, but also other regulatory regions exons. This first systematic review literature reporting on variants risk factors degenerative diseases or drug adverse effects. In particular, hypomorphic 29 bp I alleles have been linked breast solid cancer susceptibility well interindividual variability response chemotherapy. On hand, hypermorphic were associated Parkinson’s Alzheimer’s disease. D promoter impact cognitive decline, alcoholism toxicity nervous system drugs. Future studies are required fill gaps research.

Language: Английский

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The role of genetics and epigenetics in breast cancer: A comprehensive review of metastasis, risk factors, and future perspectives

Journal of Pharmaceutical Analysis, Journal Year: 2025, Volume and Issue: unknown, P. 101268 - 101268

Published: March 1, 2025

Language: Английский

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Multi-gene panel testing increases germline predisposing mutations’ detection in a cohort of breast/ovarian cancer patients from Southern Italy

Frontiers in Medicine, Journal Year: 2022, Volume and Issue: 9

Published: Aug. 11, 2022

Breast cancer is the most common neoplasia in females worldwide, about 10% being hereditary/familial and due to DNA variants cancer-predisposing genes, such as highly penetrant BRCA1/BRCA2 genes. However, their explain up 25% of suspected cases. The availability NGS methodologies has prompted research this field. With aim improve diagnostic sensitivity molecular testing, a custom designed panel 44 including also non-coding regions 5' 3' UTR regions, was set up. Here, are reported results obtained cohort 64 patients, few males, from Southern Italy. All patients had positive personal and/or familial history for breast other cancers, but tested negative routine BRCA analysis. After obtaining written informed consent, genomic sample/patient used obtain an enriched library, then analyzed by NGS. Sequencing data analysis allowed identification pathogenic 12 (19%). Interestingly, MUTYH frequently altered gene, followed RNASEL, ATM, MSH6, MRE11A, PALB2 resultsreinforce need enlarged testing beyond at least with history, strongly suggestive form. This gives hint pursue more specific precision oncology therapy.

Language: Английский

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Whole-Exome Sequencing Study of Familial Nasopharyngeal Carcinoma and Its Implication for Identifying High-Risk Individuals

JNCI Journal of the National Cancer Institute, Journal Year: 2022, Volume and Issue: 114(12), P. 1689 - 1697

Published: Sept. 6, 2022

Abstract Background Nasopharyngeal carcinoma (NPC) is closely associated with genetic factors and Epstein-Barr virus infection, showing strong familial aggregation. Individuals a family history suffer elevated NPC risk, requiring effective counseling for risk stratification individualized prevention. Methods We performed whole-exome sequencing on 502 patients 404 unaffected relatives controls. systematically evaluated the established cancer predisposition genes investigated novel susceptibility genes, making comparisons 21 other cancers in UK biobank (N = 5218). Results Rare pathogenic mutations were observed patients, including ERCC2 (1.39%), TP63 (1.00%), MUTYH (0.80%), BRCA1 (0.80%). Additionally, 6 identified. RAD54L, involved DNA repair pathway together ERCC2, MUTYH, BRCA1, showed highest frequency (4.18%) NPC. Enrichment analysis found enriched NPC, RAD54L EML2 both virus–associated cancers. Besides rare variants, common variants reported studies of sporadic also risk. top quantile variant-derived score while carrying exhibited increased (odds ratio 13.47, 95% confidence interval 6.33 to 28.68, P 1.48 × 10–11); men this group cumulative lifetime 24.19%, much higher than those bottom without (2.04%). Conclusions This study expands catalog provides potential individuals an history.

Language: Английский

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Intestinal and extraintestinal neoplasms in patients with NTHL1 tumor syndrome: a systematic review

Familial Cancer, Journal Year: 2022, Volume and Issue: 21(4), P. 453 - 462

Published: March 16, 2022

Language: Английский

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Genetic analyses of DNA repair pathway associated genes implicate new candidate cancer predisposing genes in ancestrally defined ovarian cancer cases

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: March 8, 2023

Not all familial ovarian cancer (OC) cases are explained by pathogenic germline variants in known risk genes. A candidate gene approach involving DNA repair pathway genes was applied to identify rare recurring OC not associated with from a population exhibiting genetic drift. Whole exome sequencing (WES) data of 15 13 families tested negative for were investigated 468 Filtering and prioritization criteria WES select top candidates further analyses. Candidates genotyped ancestry defined study groups 214 998 sporadic or breast (BC) 1025 population-matched controls screened additional carriers 605 cases. The also analyzed 937 diverse ancestries. Top ERCC5, EXO1, FANCC, NEIL1 NTHL1 identified 5/13 (39%) families. Collectively, 7/435 (1.6%) 1/566 (0.2%) BC versus 1/1025 (0.1%) controls. Additional 6/605 (0.9%) Tumour variant exhibited loss the wild-type allele. Carriers various these 31/937 (3.3%) ancestries 0-0.004% cancer-free strategy applying drift new predisposition

Language: Английский

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Diagnostics and treatment of ovarian cancer in the era of precision medicine - opportunities and challenges

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: Sept. 6, 2023

Due to predictions of increasing incidences and deaths from ovarian cancer, this neoplasm is a challenge for modern health care. The advent NGS technology has made it possible understand the molecular characteristics many cancers, including cancer. data obtained in research became basis development molecularly targeted therapies thus leading entry analysis into diagnostic process oncological patients. This review presents currently preclinical or clinical trials, whose promising results offer hope their use practice future. As more therapeutic options emerge, will be necessary modify regimens select best treatment given patient. New biomarkers are needed predict success planned therapy. An important aspect public testing women with familial predisposition cancer enabling patients included prevention programs. technology, despite its high throughput, poses challenges, quality material used interpretation classification sequence variants. article highlights role ongoing also era personalized medicine. spread genetic high-risk groups, introduction possibility agnostic could significantly improve situation worldwide.

Language: Английский

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Partner and localizer of BRCA2 (PALB2) pathogenic variants and ovarian cancer: A systematic review and meta-analysis.

Gynecologic Oncology, Journal Year: 2023, Volume and Issue: 177, P. 72 - 85

Published: Aug. 29, 2023

Language: Английский

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Evaluation of BRCA1/2 gene mutations in patients with high-risk breast and/or ovarian cancer in Turkey

Turkish Journal of Biochemistry, Journal Year: 2022, Volume and Issue: 47(5), P. 588 - 594

Published: Feb. 3, 2022

Abstract Objectives To find BRCA1/2 test selection criteria unique to the Turkish population, as well provide gene mutation distributions of patient population literature. Methods Genetic counseling was given 2,373 cases with a family history high-risk breast and/or ovarian cancer who applied Istanbul University, Oncology Institute, Department Cancer Genetics between 1994 and 2021 selected by NCCN Guidelines for criteria. In our clinic, screenings in genes were performed Sanger sequencing method patients admitted 2014 NGS 2015 2021. Results The overall rate group from 16.5% (391/2,373) after screening clinic. Of mutations, 57.5% (225/391) had BRCA1 mutation, 41.9% (164/391) BRCA2 0.6% (2/391) both pathogenic mutations. People diagnosed before age 60 have triple-negative 28.5% rate. Conclusions evaluated accordance genetic criteria; we discovered that all study results statistically significant (p<0.05).

Language: Английский

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The Identification by Exome Sequencing of Candidate Genes in BRCA-Negative Tunisian Patients at a High Risk of Hereditary Breast/Ovarian Cancer

Genes, Journal Year: 2022, Volume and Issue: 13(8), P. 1296 - 1296

Published: July 22, 2022

(1) Background: Germline variants in BRCA1/BRCA2 genes explain about 20% of hereditary breast/ovarian cancer (HBOC) cases. In the present paper, we aim to identify genetic determinants BRCA-negative families from South Tunisia. (2) Methods: Exome Sequencing (ES) was performed on lymphocyte DNA patients negative for BRCA mutations each Tunisian family with a high risk HBOC. (3) Results: We focus canonical associated HBOC and identified missense damage response genes, such as ATM, RAD52, RAD54; however, no PALB2, Chek2, TP53 were found. To novel candidate selected harboring loss function 17 stop-gain 11 frameshift not commonly known be predisposed Then, rare high-impact shared by at least 3 unrelated 16 gene variants. Through combined data analysis MCODE ontology KEGG pathways, short list eight (ATM, EP300, LAMA1, LAMC2, TNNI3, MYLK, COL11A2, LAMB3) created. The impact 24 survival analyzed using TCGA resulting selection five (EP300, KMT2C, RHPN2, HSPG2, CCR3) that showed significant association survival. (4) Conclusions: need validated larger cohorts investigated analyzing co-segregation affected locus-specific heterozygosity highlight their relevance risk.

Language: Английский

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