Alcohol and Dietary Folate Intake and Promoter CpG Island Methylation in Clear-Cell Renal Cell Cancer

Schouten, Leo J.; Deckers, Ivette A.G.; Brandt, Piet A. van den; Baldewijns, Marcella; Engeland, Manon van

doi:10.1080/01635581.2016.1187283

Cited by 8 publications

(3 citation statements)

References 39 publications

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“…The NEURL on the other hand acts as a tumor suppressor [45] and is involved in the Notch signaling pathway [18,46] which is critical for determination of cell fates within a wide variety of tissues by regulation of growth, differentiation, and apoptosis. Furthermore, several studies revealed that the Notch signaling pathway has an important role in the development of the mammalian kidney whereby several key members of the Notch cascade are expressed during nephrogenesis [47].…”

Section: Discussionmentioning

confidence: 99%

Development of a prognostic risk model for clear cell renal cell carcinoma by systematic evaluation of DNA methylation markers

et al. 2021

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Background Current risk models for renal cell carcinoma (RCC) based on clinicopathological factors are sub-optimal in accurately identifying high-risk patients. Here, we perform a head-to-head comparison of previously published DNA methylation markers and propose a potential prognostic model for clear cell RCC (ccRCC). Patients and methods Promoter methylation of PCDH8, BNC1, SCUBE3, GREM1, LAD1, NEFH, RASSF1A, GATA5, SFRP1, CDO1, and NEURL was determined by nested methylation-specific PCR. To identify clinically relevant methylated regions, The Cancer Genome Atlas (TCGA) was used to guide primer design. Formalin-fixed paraffin-embedded (FFPE) tissue samples from 336 non-metastatic ccRCC patients from the prospective Netherlands Cohort Study (NLCS) were used to develop a Cox proportional hazards model using stepwise backward elimination and bootstrapping to correct for optimism. For validation purposes, FFPE ccRCC tissue of 64 patients from the University Hospitals Leuven and a series of 232 cases from The Cancer Genome Atlas (TCGA) were used. Results Methylation of GREM1, GATA5, LAD1, NEFH, NEURL, and SFRP1 was associated with poor ccRCC-specific survival, independent of age, sex, tumor size, TNM stage or tumor grade. Moreover, the association between GREM1, NEFH, and NEURL methylation and outcome was shown to be dependent on the genomic region. A prognostic biomarker model containing GREM1, GATA5, LAD1, NEFH and NEURL methylation in combination with clinicopathological characteristics, performed better compared to the model with clinicopathological characteristics only (clinical model), in both the NLCS and the validation population with a c-statistic of 0.71 versus 0.65 and a c-statistic of 0.95 versus 0.86 consecutively. However, the biomarker model had limited added prognostic value in the TCGA series with a c-statistic of 0.76 versus 0.75 for the clinical model. Conclusion In this study we performed a head-to-head comparison of potential prognostic methylation markers for ccRCC using a novel approach to guide primers design which utilizes the optimal location for measuring DNA methylation. Using this approach, we identified five methylation markers that potentially show prognostic value in addition to currently known clinicopathological factors.

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Section: Discussionmentioning

confidence: 99%

Development of a prognostic risk model for clear cell renal cell carcinoma by systematic evaluation of DNA methylation markers

et al. 2021

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“…MSP primer design was based on the MBD-affinity massive parallel sequencing data. Detailed information on primer sequences and MSP conditions are available elsewhere 24 .…”

Section: Methodsmentioning

confidence: 99%

Germline polymorphisms in the Von Hippel-Lindau and Hypoxia-inducible factor 1-alpha genes, gene-environment and gene-gene interactions and renal cell cancer

Pol

Brandt

Engeland

et al. 2020

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We investigated the relationship between germline single nucleotide polymorphisms (Snps) in Von Hippel-Lindau (VHL) and Hypoxia-inducible factor 1-alpha (HIF1A), and their gene-environment and gene-gene interactions, and clear-cell Rcc (ccRcc) risk. furthermore, we assessed the relationship between VHL Snps and VHL promoter methylation. three VHL polymorphisms and one HIF1A polymorphism were genotyped in the Netherlands Cohort Study. In 1986, 120,852 participants aged 55-69 completed a self-administered questionnaire on diet and lifestyle and toenail clippings were collected. Toenail DNA was genotyped using the Sequenom MassARRAY platform. After 20.3 years, 3004 subcohort members and 406 RCC cases, of which 263 ccRCC cases, were eligible for multivariate case-cohort analyses. VHL_rs779805 was associated with RCC (Hazard Ratio (HR) 1.53; 95% Confidence Interval (CI) 1.07-2.17) and ccRCC risk (HR 1.88; 95% CI 1.25-2.81). No associations were found for other SNPs. Potential gene-environment interactions were found between alcohol consumption and selected SNPs. However, none remained statistically significant after multiple comparison correction. no gene-gene interactions were observed between VHL and HIF1A. VHL promoter methylation was not associated with VHL Snps. VHL SNPs may increase (cc)RCC susceptibility. No associations were found between gene-environment and gene-gene interactions and (cc)Rcc risk and between VHL promoter methylation and VHL Snps. Genetic and epigenetic alterations in the Von Hippel-Lindau (VHL) gene are important drivers of carcinogenesis in clear-cell renal cell carcinoma (ccRCC) 1. For sporadic ccRCC, biallelic inactivation of VHL because of rare, but highly penetrant, somatic mutations is relatively common 2,3. Previous studies have estimated that 50-82% of patients with sporadic ccRCC have a mutation in the VHL gene 4-8. The VHL gene encodes the VHL tumor suppressor protein (pVHL). Inactivation of pVHL leads to the unchecked accumulation of hypoxia-inducible factor 1 alpha (HIF1A), which facilitates oxygen delivery, adaptation to oxygen deprivation and angiogenesis 1,9. Therefore, genetic or epigenetic alterations in VHL and HIF1A may lead to enhanced cell survival and carcinogenesis. In contrast to the rare, but highly penetrant, sequence alterations leading to VHL loss, some germline Single Nucleotide Polymorphisms (SNPs) are highly frequent, but have a low penetrance. In general, SNPs account for many different phenotypes as they may alter disease susceptibility by affecting the gene's function 10. Genome-wide

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“…The 13 papers were published between 1997 and 2018 and they included a total of 13 different study populations (Table 1) [17][18][19][20][21][22][23][24][25][26][27][28][29]. Five of these studies were conducted in Europe, six were in North America, one in Australia, and one in South America.…”

Section: Study Characteristicsmentioning

confidence: 99%

Components of one-carbon metabolism and renal cell carcinoma: a systematic review and meta-analysis

et al. 2020

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Purpose Little is known about the aetiology of renal cell carcinoma (RCC). Components of one-carbon (1C) metabolism, which are required for nucleotide synthesis and methylation reactions, may be related to risk of RCC but existing evidence is inconclusive. We conducted a systematic review and independent exposure-specific meta-analyses of dietary intake and circulating biomarkers of 1C metabolites and RCC risk. Methods Medline and Embase databases were searched for observational studies investigating RCC or kidney cancer incidence or mortality in relation to components of 1C metabolism and 12 eligible articles were included in the meta-analyses. We used Bayesian meta-analyses to estimate summary relative risks (RRs) and 95% credible intervals (CrIs) comparing the highest versus lowest categories as well as the between-study heterogeneity. Results We did not find convincing evidence of an association between any exposure (riboflavin, vitamin B 6 , folate, vitamin B 12 , methionine, homocysteine, choline, or betaine) and RCC risk. However, vitamin B 6 biomarker status did have a protective (RR = 0.62) but imprecise (95% CrI 0.39-1.14) effect estimate and folate intake had a notable association as well (RR = 0.85, 95% CrI 0.71-1.01). Conclusion There was a lack of precision due largely to the low number of studies. Further investigation is warranted, especially for folate and vitamin B 6 , which had consistent suggestive evidence of a protective effect for both dietary intake and biomarker status. A unique strength of this review is the use of Bayesian meta-analyses which allowed for robust estimation of between-study heterogeneity.

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Alcohol and Dietary Folate Intake and Promoter CpG Island Methylation in Clear-Cell Renal Cell Cancer

Cited by 8 publications

References 39 publications

Development of a prognostic risk model for clear cell renal cell carcinoma by systematic evaluation of DNA methylation markers

Development of a prognostic risk model for clear cell renal cell carcinoma by systematic evaluation of DNA methylation markers

Germline polymorphisms in the Von Hippel-Lindau and Hypoxia-inducible factor 1-alpha genes, gene-environment and gene-gene interactions and renal cell cancer

Components of one-carbon metabolism and renal cell carcinoma: a systematic review and meta-analysis

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