Alcohol consumption and mutations or promoter hypermethylation of the von Hippel-Lindau gene in renal cell carcinoma

L.J. Schouten, B.A.C. van Dijk, E. Oosterwijk, M. van Engeland, C.A. Hulsbergen van Kaa, L.A. Kiemeney, R.A. Goldbohm, A.D.M. Kester, S. de Voge, J.A. Schalken, P.A. van den Brandt

Research output: Contribution to journalArticleAcademicpeer-review

171 Downloads (Pure)

Abstract

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 WHO 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, 0.1.7]. 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. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3543-50)
Original languageEnglish
Pages (from-to)3543-3550
JournalCancer Epidemiology Biomarkers & Prevention
Volume17
Issue number12
DOIs
Publication statusPublished - 1 Jan 2008

Cite this