Hypertension, antihypertensives and mutations in the Von Hippel–Lindau gene in renal cell carcinoma: results from the Netherlands Cohort Study

Schouten, Leo J.; Dijk, B.; Oosterwijk, Egbert; Kaa, C.A. Hulsbergen van de; Kiemeney, Lambertus A.; Goldbohm, R.A.; Schalken, Jack A.; Brandt, Piet A. van den

doi:10.1097/01.hjh.0000186023.74245.48

Cited by 28 publications

(27 citation statements)

References 37 publications

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“…In two prospective studies, antihypertensive treatment was associated with higher risk of renal cell cancer (Fraser et al, 1990;Heath et al, 1997), but others found no association (Grove et al, 1991;Flaherty et al, 2005;Schouten et al, 2005). One large study linking prescriptions and cancer registration in Denmark indicated that antihypertensive medication may increase risk, but was interpreted as being due to confounding by underlying hypertension (Fryzek et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…In men, there was no association with blood pressure. The association of blood pressure with risk of renal cell cancer has been investigated in a number of cohort (Fraser et al, 1990;Grove et al, 1991;Coughlin et al, 1997;Heath et al, 1997;Chow et al, 2000;Choi et al, 2005;Flaherty et al, 2005;Fryzek et al, 2005;Lindgren et al, 2005;Schouten et al, 2005) and case -control (McLaughlin et al, 1995;Yuan et al, 1998;Shapiro et al, 1999) studies, using as principal exposure variable either recorded blood pressure or reported hypertension. In men, recorded blood pressure has shown a convincing exposure -response gradient related to renal cell cancer risk (Coughlin et al, 1997;Chow et al, 2000).…”

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confidence: 99%

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Blood pressure and renal cancer risk: the HUNT Study in Norway

et al. 2007

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In a prospective study of 36 728 women and 35 688 men during 18 years of follow-up, compared to systolic pressure o130 mm Hg, levels of 130 -149, 150 -169 and X170 mm Hg in women were associated with relative risks of renal cell cancer of 1.7, 2.0 and 2.0, respectively (P for linear trend, 0.11). In men, there was no association with blood pressure. The association of blood pressure with risk of renal cell cancer has been investigated in a number of cohort (Fraser et al, 1990;Grove et al, 1991;Coughlin et al, 1997;Heath et al, 1997;Chow et al, 2000;Choi et al, 2005;Flaherty et al, 2005;Fryzek et al, 2005;Lindgren et al, 2005;Schouten et al, 2005) and case -control (McLaughlin et al, 1995;Yuan et al, 1998;Shapiro et al, 1999) studies, using as principal exposure variable either recorded blood pressure or reported hypertension. In men, recorded blood pressure has shown a convincing exposure -response gradient related to renal cell cancer risk (Coughlin et al, 1997;Chow et al, 2000). In women, however, only reported history of hypertension has been studied as the main exposure variable. In one cohort (Flaherty et al, 2005) and two case -control studies (Yuan et al, 1998;Shapiro et al, 1999), history of hypertension was associated with increased risk. Documenting the presence or the lack of an exposure -response gradient in women is important, and might promote a better probing of the underlying mechanism of the association.In this prospective study of 36 728 women and 35 688 men, we report on the association of blood pressure measured at baseline with renal cell cancer risk during 18 years of follow-up, together with that related to ever use of blood pressure medication. MATERIALS AND METHODSIn 1984, 85 100 individuals were invited to the Nord Trøndelag Health Study (the HUNT Study) in Norway, and 75 058 (88.2 percent) accepted the invitation, filled in a self-administered questionnaire, and attended a clinical examination (Holmen et al, 1991;Ellekjaer et al, 2000). Briefly, information included smoking status and standardised measurements of blood pressure, body height and weight. The study was approved by the Regional Committee for Ethics in medical research, and by the Norwegian Data Inspectorate.This study was restricted to participants without prevalent cancer who had complete information on blood pressure and body mass index. Blood pressure was measured using calibrated mercury manometers with standard cuff size (Holmen et al, 1991). We divided systolic pressure (in mm Hg) into the following categories: o130 (reference), 130 -149, 150 -169 and X170, and diastolic pressure (in mm Hg) into the following: o85 (reference), 85 -94, 95 -104 and X105. Information on use of antihypertensive medication was derived from the question 'do you use or have you ever used blood pressure medication?' Body mass index was calculated as weight (in kg) divided by the squared value of height (in metres), and grouped into four categories: o18.5, 18.5 -24.9, 25 -29.9 and X30. Information on smoking was categorised as never, former o...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Blood pressure and renal cancer risk: the HUNT Study in Norway

et al. 2007

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“…Cigarette smoking was associated with renal cell cancer risk for men but not specifically with VHL gene mutations, irrespective of sex, suggesting that smoking may cause renal cell cancer independent of VHL gene mutations (58). With respect to hypertension and use of antihypertensive medications, the association of hypertension was stronger in renal cell cancer cases with VHL gene mutations, whereas use of diuretics was associated with renal cell cancer without VHL gene mutations (59). Results were suggestive of higher relative risks for wildtype VHL tumors with a-carotene, h-cryptoxanthin, folate, and supplemental vitamin C and multivitamin intake (60).…”

Section: Discussionmentioning

confidence: 92%

Alcohol Consumption and Mutations or Promoter Hypermethylation of thevon Hippel–LindauGene in Renal Cell Carcinoma

Schouten¹,

Dijk²,

Oosterwijk

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Alcohol consumption has been associated with a decreased risk for renal cell cancer in several studies. We investigated whether alcohol is associated with (epi)genetic changes of the von Hippel -Lindau (VHL) gene in renal cell cancer. The Netherlands Cohort Study (NLCS) on Diet and Cancer started in 1986 (n = 120,852) and uses the case-cohort method. After 11.3 years of follow-up, 314 renal cell cancer cases and 4,511 subcohort members were available for analysis. DNA was isolated from paraffin-embedded tumor tissue from 235 cases. VHL mutations were analyzed by sequencing, whereas VHL promoter methylation was analyzed using methylation-specific PCR. In multivariate analysis, hazard ratios of renal cell cancer for cohort members who consumed up to 5, 15, 30, and z30 g of alcohol per day were 0.72, 0.64, 0.81, and 0.69, respectively, compared with nondrinkers [95% confidence interval (95% CI) for the z30 category, 0.44-1.07; P for trend, 0.17]. Alcohol intake from beer, wine, and liquor was associated with decreased risks for renal cell cancer, although not statistically significant. Hazard ratios were not different for clear-cell renal cell cancer with and without VHL mutations, except for alcohol from beer, which was associated with an increased risk for clear-cell renal cell cancer without VHL mutations (hazard ratio for z5 g of alcohol from beer compared with nondrinkers, 2.74; 95% CI, 1.35-5.57). Alcohol was associated with a decreased risk for clear-cell renal cell cancer without VHL gene promoter methylation (hazard ratio for >15 g compared with nondrinkers, 0.58; 95% CI, 0.34-0.99). In this study, a not statistically significant inverse association was observed between alcohol and renal cell cancer. There was no statistical significant heterogeneity by VHL mutation or methylation status. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3543 -50)

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“…103 Several [55][56][57]63,106 cohort studies have demonstrated an increased risk even after exclusion of the early years of follow-up, when early stage, prediagnostic renal tumors may themselves lead to elevated blood pressure. Recent fi ndings from the Netherlands cohort study 105 suggest that the association with hypertension may be stronger among the small fraction of sporadic renal cell cancer patients with von Hippel-Lindau gene mutations, but this needs to be confi rmed in future studies.…”

Section: Hypertension and Antihypertensive Medicationsmentioning

confidence: 97%

“…101,102 While it is diffi cult to separate the effects of hypertension or its treatment on renal cell cancer risk, as they are highly correlated variables, the collective epidemiologic evidence to date suggests that it is hypertension itself that is the determinant. Most studies have reported risks for renal cell cancer associated with either recorded blood pressure or reported hypertension ranging between 1.2 and 2 or greater, 48,51,[54][55][56]62,68,69,72,[103][104][105][106] although not all of the studies were able to adjust for the effect of antihypertensive medications. Dose-response relations between measured blood pressure level and renal cell cancer risk have been reported, 54,56,106 although only one of these studies provided data on women and considered the effect of antihypertensive medication.…”

Section: Hypertension and Antihypertensive Medicationsmentioning

confidence: 99%

Epidemiologic characteristics and risk factors for renal cell cancer

McLaughlin¹

2009

CLEP

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Abstract:Incidence rates of renal cell cancer, which accounts for 85% of kidney cancers, have been rising in the United States and in most European countries for several decades. Family history is associated with a two-to four-fold increase in risk, but the major forms of inherited predisposition together account for less than 4% of renal cell cancers. Cigarette smoking, obesity, and hypertension are the most consistently established risk factors. Analgesics have not been convincingly linked with renal cell cancer risk. A reduced risk of renal cell cancer among statin users has been hypothesized but has not been adequately studied. A possible protective effect of fruit and vegetable consumption is the only moderately consistently reported dietary fi nding, and, with the exception of a positive association with parity, evidence for a role of hormonal or reproductive factors in the etiology of renal cell cancer in humans is limited. A recent hypothesis that moderate levels of alcohol consumption may be protective for renal cell cancer is not strongly supported by epidemiologic results, which are inconsistent with respect to the categories of alcohol consumption and the amount of alcohol intake reportedly associated with decreased risk. For occupational factors, the weight of the evidence does not provide consistent support for the hypotheses that renal cell cancer may be caused by asbestos, gasoline, or trichloroethylene exposure. The established determinants of renal cell cancer, cigarette smoking, obesity, and hypertension, account for less than half of these cancers. Novel epidemiologic approaches, including evaluation of gene-environment interactions and epigenetic mechanisms of inherited and acquired increased risk, are needed to explain the increasing incidence of renal cell cancer. Keywords: renal cell cancer, epidemiology, risk factor, review Descriptive epidemiologyKidney cancer is the ninth most common cancer in developed countries.1 Approximately 85% of kidney cancers are renal parenchyma (renal cell) cancers, while the remainder for the most part are urothelial cancers of the renal pelvis.2 Approximately 80% of renal cell cancers are clear cell adenocarcinomas, the remainder being papillary (∼15%), chromophobe (∼5%), and collecting duct carcinomas (Ͻ1%). Both renal cell and renal pelvis cancers are about twice as common among men as among women, [1][2][3] with the mean age at diagnosis in the early 60s for renal cell cancer and in the late 60s for renal pelvis cancer. For renal pelvis cancer, there is a strong tendency to develop multiple transitional epithelial tumors, particularly in the urinary bladder and ureter. 4 For the most part, renal pelvis cancer parallels bladder cancer in epidemiologic characteristics and risk factors and has been addressed by the authors elsewhere.

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Hypertension, antihypertensives and mutations in the Von Hippel–Lindau gene in renal cell carcinoma: results from the Netherlands Cohort Study

Cited by 28 publications

References 37 publications

Blood pressure and renal cancer risk: the HUNT Study in Norway

Blood pressure and renal cancer risk: the HUNT Study in Norway

Alcohol Consumption and Mutations or Promoter Hypermethylation of thevon Hippel–LindauGene in Renal Cell Carcinoma

Epidemiologic characteristics and risk factors for renal cell cancer

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