13 results on '"von Hippel Lindau protein"'
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2. Genetic causes of erythrocytosis and the oxygen-sensing pathway.
- Author
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Lee, Frank S.
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POLYCYTHEMIA ,ERYTHROCYTE disorders ,DIFFERENTIAL diagnosis ,ERYTHROCYTES ,ERYTHROPOIETIN ,GENETIC mutation ,DIAGNOSIS - Abstract
Summary: Idiopathic erythrocytosis is an uncommon disease, and is defined by an increase in red blood cell mass. The differential diagnosis of erythrocytosis is extensive, and can be divided into primary and secondary forms. Primary erythrocytoses are due to intrinsic defects in erythroid precursor cells and are characterized by low erythropoietin levels. Secondary erythrocytoses are extrinsic to erythroid progenitors and are characterized by either high or inappropriately normal erythropoietin levels. A distinct subset of secondary erythrocytoses are due to genetic mutations in key proteins of the oxygen-sensing pathway. These proteins constitute the core molecular machinery of oxygen-sensing with respect to red blood cell control. Apart from assigning physiologic roles for these proteins, studies of these rare mutations have (i) revealed the exquisite sensitivity of this pathway to genetic perturbations, (ii) highlighted important functional regions of the proteins, and (iii) provided a basis for potentially targeting this pathway for therapeutic benefit. [Copyright &y& Elsevier]
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- 2008
- Full Text
- View/download PDF
3. Proteasomal Activity in Placentas from Women with Preeclampsia and Intrauterine Growth Restriction: Implications for Expression of HIF-α Proteins.
- Author
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Rajakumar, A., Michael, H.M., Daftary, A., Jeyabalan, A., Gilmour, C., and Conrad, K.P.
- Subjects
HYPOXEMIA ,PLACENTA ,PREECLAMPSIA ,PREGNANT women ,GENE expression ,TRANSCRIPTION factors - Abstract
Abstract: Hypoxia-inducible transcription factor-1α and -2α (HIF-α) proteins and regulated genes are increased in preeclamptic (PE) placentas. Although placental hypoxia likely stabilizes HIF-α proteins, we previously reported that there is also a defect in oxygen-dependent reduction of HIF-α proteins in PE relative to normal pregnant (NP) placentas that could contribute to their over-expression. After a 4-h exposure to 2% oxygen, placental villous explants were exposed to 21% oxygen over 90min. As assessed by Western analysis, the defective oxygen-dependent reduction of HIF-1α protein in villous explants from PE placenta was unaffected by the protein synthesis inhibitor, cycloheximide. However, after incubation with the proteasomal inhibitor, clasto-lactacystin, oxygen-dependent reduction of HIF-1α protein was markedly and similarly impaired in the villous explants from both normal and PE placentas. Thus, impairment of protein degradation rather than increased synthesis causes inadequate oxygen-dependent reduction of HIF-1α protein in PE placentas. Immunoprecipitation studies revealed comparable association of HIF-1α with von Hippel Lindau (VHL) protein in placentas from NP and PE women. Furthermore, prolyl hydroxylase-3 protein was appropriately upregulated in the PE placentas as determined by Western analysis paralleling the increases of HIF-α proteins. These results suggest that molecular events leading to the formation of the HIF-1α:VHL:ubiquitin ligase complex are most likely not impaired in PE placentas. Finally, proteasomal trypsin, chymotrypsin, and peptidyl glutamyl-like activities were significantly reduced by approximately 1/3 in PE placentas by using specific peptide substrates coupled to a fluorescent tag. Unexpectedly, however, they were even further decreased in placentas from normotensive women delivering growth restricted babies >37weeks gestation–placentas which do not have elevated HIF-α proteins. In conclusion, accumulation of HIF-α proteins in PE placentas may occur as a consequence of both increased formation secondary to relative ischemia/hypoxia and reduced degradation after reperfusion/oxygenation consequent to proteasomal dysfunction. In contrast, in placentas from normotensive women delivering growth restricted babies >37weeks gestation, proteasomal activity, albeit markedly reduced, is adequate to cope with degradation of HIF-α proteins, which have not been increased by an hypoxic environment. [Copyright &y& Elsevier]
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- 2008
- Full Text
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4. Genetically heterogeneous origins of idiopathic erythrocytosis.
- Author
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Percy, Melanie J.
- Subjects
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POLYCYTHEMIA , *ERYTHROPOIETIN , *HYPOXEMIA , *HEMATOLOGY , *BONE marrow diseases - Abstract
The idiopathic erythrocytosis (IE) group of disorders is defined by an absolute increase in red cell mass and hematocrit without elevation of the megakaryocytic or granulocytic lineages. It is associated with a wide range of serum erythropoietin (Epo) levels and broadly falls into groups of raised/inappropriately normal or low/undetectable Epo levels. A spectrum of molecular defects has been described in association with IE, which reflects the heterogeneity of this disorder. To date the most common identified cause of IE has been mutations in the von Hippel Landau (VHL) protein, which results in aberrant oxygen sensing and dysregulated Epo production. Studying the molecular basis of IE will provide insights into the control of Epo synthesis and Epo-induced signaling pathways. [ABSTRACT FROM AUTHOR]
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- 2007
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- View/download PDF
5. Expression of von Hippel Lindau (pVHL) Protein in Placentae from Normal Pregnant Women and Women with Preeclampsia.
- Author
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Rajakumar, A., Doty, K., Daftary, A., Markovic, N., and Conrad, K.P.
- Subjects
HYPOXEMIA ,INFLUENCE of altitude ,TRANSCRIPTION factors ,PROTEINS ,PLACENTA - Abstract
The hypoxia inducible transcription factors, HIF-1α and -2α proteins, are overexpressed in placentae from women with preeclampsia (Biol Reprod 2001;64:499–506; Biol Reprod 2001;64:1019–1020). Normally, these proteins are regulated in an oxygen-dependent manner being rapidly degraded by the ubiquitin-mediated proteasomal pathway. Recent studies have shown that the tumor suppressor protein, von Hippel Lindau (VHL), targets HIF for ubiquitinylation under nonhypoxic conditions. The objectives of the present work were: (1) to investigate VHL protein expression in normal pregnant (NP), preeclamptic (PE), and preterm (without PE) placentae, (2) to test whether VHL protein is hypoxia inducible in term and first trimester placental villous explants, and (3) to analyze the ontogeny of VHL protein expression in the human placenta. To begin evaluating the potential contribution of VHL to HIF overexpression in preeclamptic placentae, we analyzed the levels of the VHL protein in both normal and preeclamptic placentae (n =7 each). We hypothesized a deficiency of VHL protein in preeclamptic placentae. Eight biopsy sites were tested in each placenta and protein extracts were made. Western analysis was performed using VHL specific antibodies. Human renal adenocarcinoma (ACHN) cell extracts and extracts from COS-7 cells transfected with a VHL expression vector were used as positive controls. In a total of 112 biopsy sites that were analyzed (56 each for normal and preeclamptic placentae), the composite densitometry ratios (PE/NP) for the long (28kDa) and short (19kDa) forms of VHL were 1.09±0.2 and 1.16±0.11, respectively (both p =NS vs 1.0). A ratio of 1.0 indicates equal expression by preeclamptic and normal placentae. The same placentae exhibited composite densitometry (PE/NP) ratios of 1.97±0.23 and 1.68±0.20 for HIF-1α and -2α proteins, respectively (both p <0.05 vs 1.0). In a separate analysis, the protein expression of the short form of VHL was also comparable among NP, PE and preterm (n =6) placentae. VHL immunoreactivity was localized to cells within the basal plate and the syncytiotrophoblast. Despite induction of HIF proteins by hypoxia in first and term villous explants, there was no significant upregulation of VHL proteins. Finally, the expression of both the short and long forms of VHL protein decreased with gestational age (both p <0.05 by ANOVA), and in villous tissue from first trimester placentae VHL immunoreactivity was predominantly localized to the cytotrophoblast. These results suggest that (1) deficiency of VHL protein does not account for HIF-α overexpression in preeclamptic placentae, (2) VHL protein is not regulated by hypoxia in either first trimester or term placental villous explants, and (3) VHL protein expression in the placenta decreases as a function of gestational age. [Copyright &y& Elsevier]
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- 2006
- Full Text
- View/download PDF
6. Genetic analysis of a family with Von Hippel-Lindau syndrome
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Lafuente-Sanchis A, Cuevas JM, Alemany P, Cremades A, and Zúñiga Á
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von Hippel Lindau protein ,mutational analysis ,adrenal tumor ,Male ,von Hippel-Lindau Disease ,endocrine system diseases ,hemangioblastoma ,DNA Mutational Analysis ,Adrenal Gland Neoplasms ,Mutation, Missense ,cerebellum tumor ,arginine ,genetic analysis ,Pheochromocytoma ,urologic and male genital diseases ,Article ,pancreas tumor ,dominant gene ,Humans ,Point Mutation ,guanine ,genetics ,exon ,gene mutation ,human ,Cerebellar Neoplasms ,neoplasms ,VHL gene ,von Hippel Lindau disease ,Germ-Line Mutation ,Genes, Dominant ,Family Health ,missense mutation ,Exons ,female genital diseases and pregnancy complications ,Pancreatic Neoplasms ,Neuroendocrine Tumors ,female ,germline mutation ,Amino Acid Substitution ,Von Hippel-Lindau Tumor Suppressor Protein ,Mutation ,neuroendocrine tumor - Abstract
Von Hippel-Lindau syndrome (VHL) is an autosomal dominant inherited disease associated with mutations in the VHL tumour suppressor gene located on chromosome 3p25. VHL is characterized by the development of multiple malignant and benign tumours in the central nervous system and internal organs, including liver, pancreas and the adrenal gland. More than 823 different mutations of the VHL gene have currently been identified. In the present study we describe the case of a family affected by VHL treated at the University Hospital of La Ribera and the results of the genetic analysis of three relatives, identifying the mutation R167G in exon 3 of VHL gene as the cause of VHL syndrome in this family. © 2016 Sociedad Española de Anatomía Patológica
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- 2017
7. Body Mass Index and von Hippel-Lindau Gene Mutations in Clear-cell Renal Cancer: Results of the Netherlands Cohort Study on Diet and Cancer
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R. Alexandra Goldbohm, Egbert Oosterwijk, Christina A. Hulsbergen-van de Kaa, Eszter Hudak, Boukje A.C. van Dijk, Leo J. Schouten, Kim M. Smits, Piet A. van den Brandt, Bas A.J. Verhage, Pathologie, Epidemiologie, RS: CAPHRI School for Public Health and Primary Care, RS: GROW - School for Oncology and Reproduction, and TNO Kwaliteit van Leven
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Male ,Oncology ,von Hippel-Lindau Disease ,Genetics and epigenetic pathways of disease [NCMLS 6] ,Epidemiology ,cancer risk ,Gene mutation ,urologic and male genital diseases ,Body Mass Index ,Cohort Studies ,Risk Factors ,gene mutation ,Prospective cohort study ,Netherlands ,clear cell carcinoma ,Hazard ratio ,article ,kidney cancer ,weight gain ,Middle Aged ,cohort analysis ,Kidney Neoplasms ,female genital diseases and pregnancy complications ,female ,priority journal ,risk factor ,Health ,Leefomgeving en gezondheid ,Female ,wild type ,prospective study ,Cohort study ,von Hippel Lindau protein ,Adult ,medicine.medical_specialty ,Nutritional Status ,Young Adult ,Translational research [ONCOL 3] ,Internal medicine ,Confidence Intervals ,medicine ,Humans ,controlled study ,human ,Von Hippel–Lindau disease ,Risk factor ,Carcinoma, Renal Cell ,neoplasms ,VHL Mutations ,business.industry ,medicine.disease ,major clinical study ,body mass ,Diet ,Clear cell renal cell carcinoma ,Clear-cell Renal Cancer ,Endocrinology ,age ,Mutation ,business ,Body mass index - Abstract
Contains fulltext : 88671.pdf (Publisher’s version ) (Closed access) PURPOSE: Body mass index (BMI) is an important risk factor for clear-cell renal cancer (cc-RCC). A common molecular alteration in cc-RCC is loss-of-function of the von Hippel-Lindau (VHL) gene. We evaluated the association between BMI and VHL mutations in cc-RCC by using data from the Netherlands Cohort Study (NLCS), a prospective study, which comprises 120,852 persons. METHODS: After 11.3 years of follow-up, 337 incident RCC cases were identified; 185 cc-RCC cases were included for analyses. RESULTS: A high BMI at baseline was associated with an increased risk of cc-RCC with or without VHL mutations (per 1 kg/m(2): hazard ratio [HR] = 1.09, 95% confidence interval [CI]: 1.02-1.16 and HR = 1.08, 95%CI: 1.01-1.15, respectively). BMI at age 20 was only associated with an increased risk of cc-RCC with VHL mutations (per 1 kg/m(2): HR =1.09, 95% CI: 1.03-1.16). In contrast, BMI gain since age 20 was only associated with an increased risk in VHL wild-type cases (per 1 kg/m(2): HR = 1.10, 95% CI: 1.03-1.19). CONCLUSION: Our findings indicate that BMI may be differently associated with subtypes of RCC based on VHL mutations. 01 mei 2010
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- 2010
8. Body Mass Index and von Hippel-Lindau Gene Mutations in Clear-cell Renal Cancer: Results of the Netherlands Cohort Study on Diet and Cancer
- Subjects
von Hippel Lindau protein ,Adult ,Male ,von Hippel-Lindau Disease ,Nutritional Status ,cancer risk ,urologic and male genital diseases ,Body Mass Index ,Cohort Studies ,Young Adult ,Risk Factors ,Confidence Intervals ,Humans ,controlled study ,gene mutation ,human ,neoplasms ,Netherlands ,clear cell carcinoma ,VHL Mutations ,Carcinoma ,article ,kidney cancer ,Renal Cell ,weight gain ,Middle Aged ,cohort analysis ,major clinical study ,female genital diseases and pregnancy complications ,body mass ,Kidney Neoplasms ,Diet ,Clear-cell Renal Cancer ,female ,age ,priority journal ,risk factor ,Health ,Mutation ,Leefomgeving en gezondheid ,wild type ,prospective study - Abstract
Purpose: Body mass index (BMI) is an important risk factor for clear-cell renal cancer (cc-RCC). A common molecular alteration in cc-RCC is loss-of-function of the von Hippel-Lindau (VHL) gene. We evaluated the association between BMI and VHL mutations in cc-RCC by using data from the Netherlands Cohort Study (NLCS), a prospective study, which comprises 120,852 persons. Methods: After 11.3 years of follow-up, 337 incident RCC cases were identified; 185 cc-RCC cases were included for analyses. Results: A high BMI at baseline was associated with an increased risk of cc-RCC with or without VHL mutations (per 1 kg/m2: hazard ratio [HR] = 1.09, 95% confidence interval [CI]: 1.02-1.16 and HR = 1.08, 95%CI: 1.01-1.15, respectively). BMI at age 20 was only associated with an increased risk of cc-RCC with VHL mutations (per 1 kg/m2: HR =1.09, 95% CI: 1.03-1.16). In contrast, BMI gain since age 20 was only associated with an increased risk in VHL wild-type cases (per 1 kg/m2: HR = 1.10, 95% CI: 1.03-1.19). Conclusion: Our findings indicate that BMI may be differently associated with subtypes of RCC based on VHL mutations. © 2010 Elsevier Inc.
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- 2010
9. Carotenoid and vitamin intake, von Hippel-Lindau gene mutations and sporadic renal cell carcinoma
- Author
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Dijk, B.A.C. van, Schouten, L.J., Oosterwijk, E., Hulsbergen van de, Kaa, C.A., Kiemeney, L.A.L.M., Goldbohm, R.A., Schalken, J.A., Brandt, P.A. van den, and TNO Kwaliteit van Leven
- Subjects
von Hippel Lindau protein ,Male ,Risk ,von Hippel-Lindau Disease ,kidney carcinoma ,Von Hippel-Lindau gene mutations ,cancer risk ,urologic and male genital diseases ,alpha tocopherol ,Cohort Studies ,folic acid ,follow up ,Humans ,Supplements ,gene mutation ,Carcinoma, Renal Cell ,alpha carotene ,beta cryptoxanthin ,Aged ,Netherlands ,Proportional Hazards Models ,vitamin intake ,adult ,vitamin supplementation ,Vitamins ,Middle Aged ,Nutrition Surveys ,major clinical study ,Carotenoids ,female genital diseases and pregnancy complications ,Renal cell carcinoma ,body mass ,Kidney Neoplasms ,Health ,Case-Control Studies ,Dietary Supplements ,ascorbic acid ,Female - Abstract
Objective: We investigated whether dietary carotenoid and vitamin intake and supplemental vitamin use were inversely associated with RCC risk and with Von Hippel-Lindau (VHL)-gene mutations in clear-cell renal cell carcinoma (RCC). Methods: The Netherlands Cohort Study on diet and cancer (NLCS) includes 120,852 persons, who completed a self-administered food-frequency questionnaire in 1986. After 11.3 years of follow-up, 284 cases and a random sample of 4,095 persons (subcohort) with complete data were included in multivariable analyses using a case-cohort approach. VHL gene mutational analysis was complete for 225 cases. Rate ratios and corresponding 95% confidence intervals were estimated using Cox proportional hazard models, while adjusting for age, sex, smoking, body mass index, and a history of hypertension. Results: We observed no association for dietary carotenoid and vitamin intake and RCC risk, and a somewhat increased risk with supplemental vitamin E, AD, and multivitamin use. Results were suggestive of higher RRs for alpha-carotene, beta-cryptoxanthin, folate, and supplemental vitamin C and multivitamin intake for wildtype VHL tumors compared to VHL-mutated tumors. Conclusions: There was no association of carotenoid, vitamin or supplemental vitamin intake and RCC risk. These associations should be investigated by others to confirm the current observations. © 2007 Springer Science+Business Media B.V.
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- 2008
10. Carotenoid and vitamin intake, von Hippel-Lindau gene mutations and sporadic renal cell carcinoma
- Subjects
von Hippel Lindau protein ,Male ,Risk ,von Hippel-Lindau Disease ,kidney carcinoma ,Von Hippel-Lindau gene mutations ,cancer risk ,urologic and male genital diseases ,alpha tocopherol ,Cohort Studies ,folic acid ,follow up ,Humans ,Supplements ,gene mutation ,alpha carotene ,beta cryptoxanthin ,Aged ,Netherlands ,Proportional Hazards Models ,vitamin intake ,adult ,Carcinoma ,Renal Cell ,vitamin supplementation ,Vitamins ,Middle Aged ,Nutrition Surveys ,major clinical study ,Carotenoids ,female genital diseases and pregnancy complications ,Renal cell carcinoma ,body mass ,Kidney Neoplasms ,Health ,Case-Control Studies ,Dietary Supplements ,ascorbic acid ,Female - Abstract
Objective: We investigated whether dietary carotenoid and vitamin intake and supplemental vitamin use were inversely associated with RCC risk and with Von Hippel-Lindau (VHL)-gene mutations in clear-cell renal cell carcinoma (RCC). Methods: The Netherlands Cohort Study on diet and cancer (NLCS) includes 120,852 persons, who completed a self-administered food-frequency questionnaire in 1986. After 11.3 years of follow-up, 284 cases and a random sample of 4,095 persons (subcohort) with complete data were included in multivariable analyses using a case-cohort approach. VHL gene mutational analysis was complete for 225 cases. Rate ratios and corresponding 95% confidence intervals were estimated using Cox proportional hazard models, while adjusting for age, sex, smoking, body mass index, and a history of hypertension. Results: We observed no association for dietary carotenoid and vitamin intake and RCC risk, and a somewhat increased risk with supplemental vitamin E, AD, and multivitamin use. Results were suggestive of higher RRs for alpha-carotene, beta-cryptoxanthin, folate, and supplemental vitamin C and multivitamin intake for wildtype VHL tumors compared to VHL-mutated tumors. Conclusions: There was no association of carotenoid, vitamin or supplemental vitamin intake and RCC risk. These associations should be investigated by others to confirm the current observations. © 2007 Springer Science+Business Media B.V.
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- 2008
11. Hypertension, antihypertensives and mutations in the Von Hippel-Lindau gene in renal cell carcinoma: Results from the Netherlands Cohort Study
- Subjects
von Hippel Lindau protein ,Male ,hypertension ,Food and Chemical Risk Analysis ,kidney carcinoma ,cigarette smoking ,genetic analysis ,cancer risk ,urologic and male genital diseases ,genetic risk ,paraffin ,Cohort Studies ,Risk Factors ,Humans ,gene mutation ,human ,neoplasms ,Biology ,Antihypertensive Agents ,Netherlands ,Aged ,Antihypertensive medication ,diuretic agent ,adult ,Carcinoma ,Statistics ,article ,Renal Cell ,The Netherlands ,Middle Aged ,cohort analysis ,DNA isolation ,major clinical study ,female genital diseases and pregnancy complications ,Renal cell carcinoma ,body mass ,Kidney Neoplasms ,female ,Treatment Outcome ,priority journal ,Von Hippel-Lindau Tumor Suppressor Protein ,Case-Control Studies ,Mutation ,antihypertensive agent ,Cohort study ,VHL mutations ,Follow-Up Studies - Abstract
Objectives: Hypertension and/or antihypertensive medication are reported to be risk factors of renal cell carcinoma (RCC). We investigated whether these risk factors are associated with von Hippel-Lindau gene (VHL) mutations in RCC. Methods: The Netherlands Cohort Study on Diet and Cancer (NLCS) started in 1986 (n = 120 852 men and women) and uses the case-cohort methodology. After 11.3 years of follow-up, 337 RCC cases and 4774 subcohort members were available for analysis. DNA was isolated from paraffin-embedded tumour tissue for VHL analysis. Results: Cohort members who reported hypertension or use of antihypertensive medication had a slightly (non-significant) increased risk of RCC: rate ratios (RR) 1.22 [95% confidence interval (Cl), 0.94-1.58] and 1.14 (95% Cl, 0.85-1.52), respectively. RRs were adjusted for sex, age, body mass index (BMI) and cigarette smoking. Of the 235 patients for whom tumour tissue specimens were collected, 187 had a clear-cell RCC, of whom 114 had a VHL mutation. History of hypertension was associated with a non-significantly increased risk of clear-cell RCC with VHL mutations: RR = 1.34 (95% Cl, 0.87-2.07), and was not associated with the risk of clear-cell RCC without VHL mutations; RR = 0.88 (95% Cl, 0.51-1.53). Use of diuretics was associated with clear-cell RCC without VHL mutations; RR = 2.11 (95% Cl, 1.16-3.83). Conclusions: In this study non-significantly increased risks for history of hypertension and use of antihypertensive medication with RCC were observed. The association with hypertension was stronger in RCC patients with VHL mutations, while there was a positive association of diuretics use and risk of RCC without VHL mutations. © 2005 Lippincott Williams & Wilkins.
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- 2005
12. Hypertension, antihypertensives and mutations in the Von Hippel-Lindau gene in renal cell carcinoma: results from the Netherlands Cohort Study
- Author
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Leo J. Schouten, B.A.C. van Dijk, J.A. Schalken, Egbert Oosterwijk, Lambertus A. Kiemeney, R.A. Goldbohm, C.A. Hulsbergen van de Kaa, P.A. van den Brandt, Epidemiologie, RS: NUTRIM School of Nutrition and Translational Research in Metabolism, RS: CAPHRI School for Public Health and Primary Care, and TNO Kwaliteit van Leven
- Subjects
Oncology ,Male ,Genetics and epigenetic pathways of disease [NCMLS 6] ,Physiology ,Statistics as Topic ,kidney carcinoma ,cigarette smoking ,genetic analysis ,Aetiology, screening and detection [ONCOL 5] ,Gene mutation ,cancer risk ,genetic risk ,urologic and male genital diseases ,paraffin ,Cohort Studies ,Diet and cancer ,Renal cell carcinoma ,Risk Factors ,Determinants in Health and Disease [EBP 1] ,gene mutation ,Molecular diagnosis, prognosis and monitoring [UMCN 1.2] ,Netherlands ,Antihypertensive medication ,adult ,Statistics ,article ,Middle Aged ,cohort analysis ,Kidney Neoplasms ,female genital diseases and pregnancy complications ,female ,Treatment Outcome ,priority journal ,Von Hippel-Lindau Tumor Suppressor Protein ,Cohort ,Hypertension ,antihypertensive agent ,Female ,Cardiology and Cardiovascular Medicine ,Cohort study ,VHL mutations ,von Hippel Lindau protein ,medicine.medical_specialty ,hypertension ,Food and Chemical Risk Analysis ,Molecular epidemiology [NCEBP 1] ,Translational research [ONCOL 3] ,Interventional oncology [UMCN 1.5] ,Internal medicine ,Internal Medicine ,medicine ,Humans ,human ,Biology ,Carcinoma, Renal Cell ,neoplasms ,Antihypertensive Agents ,Aged ,Hereditary cancer and cancer-related syndromes [ONCOL 1] ,business.industry ,diuretic agent ,Kidney Carcinoma ,Case-control study ,The Netherlands ,medicine.disease ,DNA isolation ,major clinical study ,body mass ,Endocrinology ,Case-Control Studies ,Mutation ,business ,Body mass index ,Follow-Up Studies - Abstract
Contains fulltext : 47661.pdf (Publisher’s version ) (Closed access) OBJECTIVES: Hypertension and/or antihypertensive medication are reported to be risk factors of renal cell carcinoma (RCC). We investigated whether these risk factors are associated with von Hippel-Lindau gene (VHL) mutations in RCC. METHODS: The Netherlands Cohort Study on Diet and Cancer (NLCS) started in 1986 (n = 120 852 men and women) and uses the case-cohort methodology. After 11.3 years of follow-up, 337 RCC cases and 4774 subcohort members were available for analysis. DNA was isolated from paraffin-embedded tumour tissue for VHL analysis. RESULTS: Cohort members who reported hypertension or use of antihypertensive medication had a slightly (non-significant) increased risk of RCC: rate ratios (RR) 1.22 [95% confidence interval (CI), 0.94-1.58] and 1.14 (95% CI, 0.85-1.52), respectively. RRs were adjusted for sex, age, body mass index (BMI) and cigarette smoking. Of the 235 patients for whom tumour tissue specimens were collected, 187 had a clear-cell RCC, of whom 114 had a VHL mutation. History of hypertension was associated with a non-significantly increased risk of clear-cell RCC with VHL mutations: RR = 1.34 (95% CI, 0.87-2.07), and was not associated with the risk of clear-cell RCC without VHL mutations; RR = 0.88 (95% CI, 0.51-1.53). Use of diuretics was associated with clear-cell RCC without VHL mutations; RR = 2.11 (95% CI, 1.16-3.83). CONCLUSIONS: In this study non-significantly increased risks for history of hypertension and use of antihypertensive medication with RCC were observed. The association with hypertension was stronger in RCC patients with VHL mutations, while there was a positive association of diuretics use and risk of RCC without VHL mutations.
- Published
- 2005
13. Hypertension, antihypertensives and mutations in the Von Hippel-Lindau gene in renal cell carcinoma: Results from the Netherlands Cohort Study
- Author
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Schouten, L.J. and Schouten, L.J.
- Abstract
Objectives: Hypertension and/or antihypertensive medication are reported to be risk factors of renal cell carcinoma (RCC). We investigated whether these risk factors are associated with von Hippel-Lindau gene (VHL) mutations in RCC. Methods: The Netherlands Cohort Study on Diet and Cancer (NLCS) started in 1986 (n = 120 852 men and women) and uses the case-cohort methodology. After 11.3 years of follow-up, 337 RCC cases and 4774 subcohort members were available for analysis. DNA was isolated from paraffin-embedded tumour tissue for VHL analysis. Results: Cohort members who reported hypertension or use of antihypertensive medication had a slightly (non-significant) increased risk of RCC: rate ratios (RR) 1.22 [95% confidence interval (Cl), 0.94-1.58] and 1.14 (95% Cl, 0.85-1.52), respectively. RRs were adjusted for sex, age, body mass index (BMI) and cigarette smoking. Of the 235 patients for whom tumour tissue specimens were collected, 187 had a clear-cell RCC, of whom 114 had a VHL mutation. History of hypertension was associated with a non-significantly increased risk of clear-cell RCC with VHL mutations: RR = 1.34 (95% Cl, 0.87-2.07), and was not associated with the risk of clear-cell RCC without VHL mutations; RR = 0.88 (95% Cl, 0.51-1.53). Use of diuretics was associated with clear-cell RCC without VHL mutations; RR = 2.11 (95% Cl, 1.16-3.83). Conclusions: In this study non-significantly increased risks for history of hypertension and use of antihypertensive medication with RCC were observed. The association with hypertension was stronger in RCC patients with VHL mutations, while there was a positive association of diuretics use and risk of RCC without VHL mutations. © 2005 Lippincott Williams & Wilkins.
- Published
- 2005
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