title: Alcohol consumption and mutations or promoter hypermethylation of the von Hippel-Lindau gene in renal cell carcinoma.
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 (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 > or = 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 > or = 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 > or = 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.
authors.affiliation: Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, the Netherlands. lj.schouten@epid.unimaas.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: Manon
authors.initials: M
authors.lastname: van Engeland
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: Royle Alexandra
authors.initials: RA
authors.lastname: Goldbohm
authors.forename: Arnold
authors.initials: A
authors.lastname: Kester
authors.forename: Stefan
authors.initials: S
authors.lastname: de Vogel
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; D000428:Alcohol Drinking / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D011795:Surveys and Questionnaires; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics*
chemical_list: D051794:Von Hippel-Lindau Tumor Suppressor Protein