Prevalence of germline mutations in cancer susceptibility genes in Chinese patients with renal cell carcinoma

Feng, Huayi; Cao, Shouqing; Ouyang, Qi; Li, Huaikang; Li, Xiubin; Chen, Ke; Zhang, Xiangyi; Huang, Yan; Zhang, Xu; Ma, Xin

doi:10.21037/tau-23-32

Cited by 2 publications

(11 citation statements)

References 75 publications

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“…The data on low population incidence and RCCspecific penetrance [127] are in apparent conflict with the results of a multigene sequencing study, which revealed FH pathogenic or likely pathogenic variants in 7/254 (2.8%) RCC patients [9]. There are several other reports suggesting that germline FH gene alterations make a noticeable contribution to RCC morbidity [8,12,14,23,130].…”

Section: Fumarate Hydratase Tumor Predisposition Syndrome (Fhtps)mentioning

confidence: 82%

“…PPGLs: 1:51,667-1:77,500 (Denmark) [27] N/A 0.7-0.9%: 0.8% [9]; 0.7% [11]; 0.8% [14]; 0.9% [8,12] PPGLs: 20-43% [17,18,28] PPGLs: SDHB: 21.8%; SDHD: 43.2%; SDHC: 25% [29] SDHA: clinical series: 10-30%; population-based estimates: 0.1-4.9% [30] SDHx-associated RCCs: SDHB: 4.2%; SDHD, SDHC, SDHA: the increased risk has not been proven [29] Rarely: thyroid carcinomas, GIST, pituitary adenomas, etc.…”

Section: Prevalence Of Sdhx-associatedmentioning

confidence: 99%

“…1:500,000 (worldwide) [31] 1:176,366 (South Korea) [32] 1:3265 (Sweden) [33] 1:3234 (Pennsylvania, USA) [34] 67% [35]; 80-85% [35] 0.3-1.6%: 0.3% [11,13]; 0.4% [13]; 0.5% [10]; 1.2% [8]; 1.6% [14] RCCs: 19-21%; spontaneous pneumothorax/multiple bilateral pleural/ subpleural cysts: 82-87%; skin lesions (fibrofolliculomas, acrochordons, angiofibromas): 78-87%; colonic polyps: 21-32% [36].…”

Section: Prevalence Of Sdhx-associatedmentioning

confidence: 99%

“…The role of the other above-mentioned genes in RCC predisposition remains unproven [72]. The overall contribution of HPP-related alleles in kidney cancer incidence is below 1% [8,9,12,14]. Tumors arising in SDHx-heterozygous individuals are characterized by somatic inactivation of the remaining gene copy.…”

Section: Kidney Tumors Associated With Hereditary Paraganglioma and P...mentioning

confidence: 99%

“…1.7% [12]; 2.2% [13]; 3.2% [14] Hemangioblastomas: 25-38% [15] Pancreatic neuroendocrine tumors: 10% [16] Pheochromocytomas/ paragangliomas (PPGLs): 4-5% [17,18] 87-95% [5,19] Hypomorphic missense mutations associated with isolated PPGLs may have reduced penetrance 20% [3,5] Genotype-phenotype correlations are observed. 70% (familial HLRCC cases) [23] 0.2-5.2%: 0.2% [11]; 0.6% [13]; 1% [7,10]; 1.6% [14]; 1.8% [11]; 2.8% [9]; 5.2% [12]; Papillary type 2 RCC: 17.4% [23] Uterine leiomyomas: ~0.7% [24] Uterine leiomyomas in young patients (<30 years): 2% [25] RCCs: ~19% [26…”

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: Fumarate Hydratase Tumor Predisposition Syndrome (Fhtps)mentioning

confidence: 82%

Section: Prevalence Of Sdhx-associatedmentioning

confidence: 99%

Section: Prevalence Of Sdhx-associatedmentioning

confidence: 99%

Section: Kidney Tumors Associated With Hereditary Paraganglioma and P...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hereditary Renal Cancer Syndromes

Yanus,

Kuligina,

Imyanitov

2024

Medical Sciences

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Detection Rate and Spectrum of Pathogenic Variations in a Cohort of 83 Patients with Suspected Hereditary Risk of Kidney Cancer

Ouedraogo,

Ceruti,

Lepage

et al. 2023

Genes

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Hereditary predisposition to cancer affects about 3–5% of renal cancers. Testing criteria have been proposed in France for genetic testing of non-syndromic renal cancer. Our study explores the detection rates associated with our testing criteria. Using a comprehensive gene panel including 8 genes related to renal cancer and 50 genes related to hereditary predisposition to other cancers, we evaluated the detection rate of pathogenic variants in a cohort of 83 patients with suspected renal cancer predisposition. The detection rate was 7.2% for the renal cancer genes, which was 2.41-fold higher than the estimated 3% proportion of unselected kidney cases with inherited risk. Pathogenic variants in renal cancer genes were observed in 44.5% of syndromic cases, and in 2.7% of non-syndromic cases. Incidental findings were observed in CHEK2, MSH2, MUTYH and WRN. CHEK2 was associated with renal cancer (OR at 7.14; 95% CI 1.74–29.6; p < 0.003) in our study in comparison to the gnomAD control population. The detection rate in renal cancer genes was low in non-syndromic cases. Additional causal mechanisms are probably involved, and further research is required to find them. A study of the management of renal cancer risk for CHEK2 pathogenic variant carriers is needed.

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Prevalence of germline mutations in cancer susceptibility genes in Chinese patients with renal cell carcinoma

Cited by 2 publications

References 75 publications

Hereditary Renal Cancer Syndromes

Hereditary Renal Cancer Syndromes

Detection Rate and Spectrum of Pathogenic Variations in a Cohort of 83 Patients with Suspected Hereditary Risk of Kidney Cancer

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