Hereditary cancer syndromes

Imyanitov, Evgeny N.; Kuligina, Ekatherina Sh.; Sokolenko, Anna P.; Suspitsin, Evgeny N.; Yanus, G.A.; Iyevleva, Aglaya G.; Ivantsov, Alexandr O.; Aleksakhina, Svetlana N.

doi:10.5306/wjco.v14.i2.40

Cited by 21 publications

(19 citation statements)

References 244 publications

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“…The cancer development is triggered by the somatic inactivation of the remaining gene copy, be it a deletion (loss of heterozygosity, LOH), a point mutation, or epigenetic silencing. This two-hit mechanism, initially predicted by Alfred G. Knudson, is observed in the majority of HCSs, although some other roots have been described as well [1,2,4].…”

Section: Introductionmentioning

confidence: 84%

“…While the majority of familial tumors are caused by the transmission of an inactivating mutation in a tumor suppressor gene and require somatic inactivation of the remaining gene copy to trigger the process of malignant transformation, HPRCC is related to activating mutations in the MET oncogene. In this respect, HPRCC is similar to multiple endocrine neoplasia types 2 and 3 (also known as type 2B), which are attributed to the inherited activation of another receptor tyrosine kinase, RET [2]. MET activation is involved in the pathogenesis of several tumor types with the most well-known example being exon 14 skipping mutations in lung cancer [138].…”

Section: Hereditary Papillary Renal Cell Carcinoma (Hprcc)mentioning

confidence: 99%

“…There are a few dozen other types of HCSs; however, they have a significantly lower incidence. Indeed, the knowledge on most of the HCS types is limited to the description of several thousand or even several hundred affected individuals with many nuances remaining poorly understood [1,2].…”

Section: Introductionmentioning

confidence: 99%

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Hereditary Renal Cancer Syndromes

Yanus,

Kuligina,

Imyanitov

2024

Medical Sciences

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Familial kidney tumors represent a rare variety of hereditary cancer syndromes, although systematic gene sequencing studies revealed that as many as 5% of renal cell carcinomas (RCCs) are associated with germline pathogenic variants (PVs). Most instances of RCC predisposition are attributed to the loss-of-function mutations in tumor suppressor genes, which drive the malignant progression via somatic inactivation of the remaining allele. These syndromes almost always have extrarenal manifestations, for example, von Hippel–Lindau (VHL) disease, fumarate hydratase tumor predisposition syndrome (FHTPS), Birt–Hogg–Dubé (BHD) syndrome, tuberous sclerosis (TS), etc. In contrast to the above conditions, hereditary papillary renal cell carcinoma syndrome (HPRCC) is caused by activating mutations in the MET oncogene and affects only the kidneys. Recent years have been characterized by remarkable progress in the development of targeted therapies for hereditary RCCs. The HIF2aplha inhibitor belzutifan demonstrated high clinical efficacy towards VHL-associated RCCs. mTOR downregulation provides significant benefits to patients with tuberous sclerosis. MET inhibitors hold promise for the treatment of HPRCC. Systematic gene sequencing studies have the potential to identify novel RCC-predisposing genes, especially when applied to yet unstudied populations.

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Section: Introductionmentioning

confidence: 84%

Section: Hereditary Papillary Renal Cell Carcinoma (Hprcc)mentioning

confidence: 99%

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Hereditary Renal Cancer Syndromes

Yanus,

Kuligina,

Imyanitov

2024

Medical Sciences

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“…In recent years, several genes associated with hereditary cancer syndromes have been identified, and at least 2% of presumably healthy individuals carries highly penetrating pathogenic gene variants predisposing them to cancer [20]. Individuals with hereditary cancer syndromes have a higher risk of developing multiple primary cancers during their lifetime or may develop cancer at a younger age.…”

Section: Discussionmentioning

confidence: 99%

The Crucial Role of Hereditary Cancer Panel Testing in Unaffected Individuals with a Strong Family History of Cancer: A Retrospective Study of a Cohort of 103 Healthy Subjects

Pilenzi,

Anaclerio,

Dell’Elice

et al. 2024

Preprint

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Hereditary cancer syndromes caused by germline mutations account for 5-10% of all cancers. The finding of a genetic mutation could have far-reaching consequences for pharmaceutical therapy, personalized prevention strategies, and cascade testing. According to the National Comprehensive Cancer Network’s (NCCN) and the Italian Association of Medical Oncology (AIOM) guidelines, unaffected family members should be tested only if the affected one is unavailable. This article explores whether germline genetic testing may be offered to high-risk families for hereditary cancer even if a living affected relative is missing. A retrospective study was carried out on 103 healthy subjects tested from 2017 to 2023. We enrolled all subjects with at least two first or second-degree relatives affected by breast, ovarian, pancreatic, gastric, prostate, or colorectal cancer. All subjects were tested by Next Generation Sequencing (NGS) multi-gene panel of 27 cancer-associated genes. In the study population, 5 (about 5%) pathogenic/likely pathogenic variants (PVs/LPVs) were found while 40 (42%) had a Variant of Uncertain Significance (VUS). This study highlights the importance of genetic testing for individuals with a strong family history of hereditary malignancies. This approach would allow women who tested positive to receive tailored treatment and prevention strategies based on their personal mutation status.

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“…This information was retrieved from the MBR, the national censuses, and the longitudinal integrated database for health insurance and labor market studies. 21 Individuals with known childhood cancer predisposition syndromes other than neurocutaneous syndromes 22 , 23 or missing information on the main covariates were excluded from the analysis (eFigure 1 and eTable 1 in Supplement 1 ). Data were prepared with SAS version 9.4 (SAS Institute), whereas all analyses were performed with Stata version 14.2 (StataCorp).…”

Section: Methodsmentioning

confidence: 99%

Neurocutaneous Syndromes, Perinatal Factors, and the Risk of Childhood Cancer in Sweden

Kampitsi,

Nordgren,

Mogensen

et al. 2023

JAMA Netw Open

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ImportanceNeurocutaneous syndromes are associated with cancer predisposition and sometimes associated with perinatal factors. A better understanding of the association between neurocutaneous syndromes, perinatal factors, and childhood cancer is key for earlier cancer detection.ObjectiveTo evaluate the association of neurocutaneous syndromes and perinatal factors with childhood cancer risk in a cohort of Swedish children.Design, Setting, and ParticipantsIn this nationwide cohort study, all children and adolescents up to age 20 years, from 1973 to 2015, were identified through the Swedish National Medical Birth Register (MBR), provided they had information on both biological parents. Analyses were conducted from April 2021 through May 2023.ExposuresDiagnoses of neurocutaneous syndromes were obtained from the MBR, National Patient Register, and Cause of Death register. Perinatal factors (birth weight, gestational age, birth weight by gestational age, 5-minute Apgar score, and head circumference) were obtained from the MBR.Main Outcomes and MeasuresChildhood cancer risk (&lt;20 years at diagnosis; identified from the National Cancer Register), including leukemia, lymphoma, and central nervous system (CNS) tumors.ResultsAmong 4 173 108 included children (2 143 133 [51.4%] male, median [IQR] follow-up 20 [9.7-20] years), 1783 had neurofibromatosis type 1 (NF1), 444 tuberous sclerosis, 63 von Hippel-Lindau disease, and 39 ataxia-telangiectasia. An increased cancer risk was observed among children with any neurocutaneous syndrome (HR, 34.9; 95% CI, 30.8-39.6) and was particularly pronounced for CNS tumors (HR, 111.7; 95% CI, 96.8-128.8), except among children with ataxia-telangiectasia, where the increased risk was associated with lymphomas (HR, 233.1; 95% CI, 75.0-724.1). Leukemia risk was increased only among children with NF1 (HR, 4.1; 95% CI, 1.7-9.8). Several perinatal factors, including high birth weight, being born large for gestational age, preterm birth, low 5-minute Apgar score, and large head circumference had lesser associations with childhood cancer. Adjusting for neurocutaneous syndromes did not affect these associations.Conclusions and RelevanceIn this nationwide cohort study, neurocutaneous syndromes were associated with an increased risk of childhood cancer, especially CNS tumors. Several perinatal factors had lesser associations with childhood cancer, independently of the presence of neurocutaneous syndromes. Other biological mechanisms likely underlie the association between perinatal factors and childhood cancer.

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Hereditary cancer syndromes

Cited by 21 publications

References 244 publications

Hereditary Renal Cancer Syndromes

Hereditary Renal Cancer Syndromes

The Crucial Role of Hereditary Cancer Panel Testing in Unaffected Individuals with a Strong Family History of Cancer: A Retrospective Study of a Cohort of 103 Healthy Subjects

Neurocutaneous Syndromes, Perinatal Factors, and the Risk of Childhood Cancer in Sweden

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