title: Hypertension, antihypertensives and mutations in the Von Hippel-Lindau gene in renal cell carcinoma: results from the Netherlands Cohort Study.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Epidemiology, NUTRIM, Maastricht University, The Netherlands. lj.schouten@epid.unimass.nl
authors.forename: Leo J
authors.initials: LJ
authors.lastname: Schouten
authors.forename: Boukje A C
authors.initials: BA
authors.lastname: van Dijk
authors.forename: Egbert
authors.initials: E
authors.lastname: Oosterwijk
authors.forename: Christina A
authors.initials: CA
authors.lastname: Hulsbergen-van de Kaa
authors.forename: Lambertus A L M
authors.initials: LA
authors.lastname: Kiemeney
authors.forename: R Alexandra
authors.initials: RA
authors.lastname: Goldbohm
authors.forename: Jack A
authors.initials: JA
authors.lastname: Schalken
authors.forename: Piet A
authors.initials: PA
authors.lastname: van den Brandt
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D007680:Kidney Neoplasms / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000187:drug effects / Q000235:genetics*; D009426:Netherlands; D012307:Risk Factors; D013223:Statistics as Topic; D016896:Treatment Outcome; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics*
chemical_list: D000959:Antihypertensive Agents; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human