Alcohol consumption and mutations or promoter hypermethylation of the von Hippel-Lindau gene in renal cell carcinoma
article
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 ≥30 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 ≥30 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 ≥5 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. Copyright © 2008 American Association for Cancer Research.
Topics
Adult
Alcohol consumption
Cancer risk
Clear cell carcinoma
Controlled study
Disease association
DNA determination
Epigenetics
Gene mutation
Kidney carcinoma
Major clinical study
Risk assessment
Tumor gene
Von Hippel Lindau gene
Aged
Alcohol Drinking
Carcinoma, Renal Cell
Case-Control Studies
CpG Islands
DNA Methylation
Female
Humans
Kidney Neoplasms
Male
Middle Aged
Mutation
Proportional Hazards Models
Prospective Studies
Questionnaires
Risk Factors
Von Hippel-Lindau Tumor Suppressor Protein
TNO Identifier
241157
DOI
https://dx.doi.org/10.1158/1055-9965.EPI-08-0321
ISSN
10559965
Source
Cancer Epidemiology Biomarkers and Prevention, 17(12), pp. 3543-3550.
Pages
3543-3550
Files
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