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Alcohol Consumption and Mutations or Promoter Hypermethylation of the von Hippel–Lindau Gene in Renal Cell Carcinoma

¹ Departments of Epidemiology and ² Pathology, GROW School for Oncology and Developmental Biology, and ³ Department of Methodology and Statistics, Maastricht University, Maastricht, the Netherlands; ⁴ Departments of Urology, ⁵ Pathology, and ⁶ Epidemiology and Biostatistics, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands; and ⁷ Department of Prevention and Health, TNO Quality of Life, Leiden, the Netherlands

Requests for reprints: Leo J. Schouten, Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, the Netherlands. Phone: 31-43-3882390; Fax: 31-43-3884128. E-mail: lj.schouten{at}epid.unimaas.nl

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. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3543–50)