Alcohol intake has been found to be associated with a decreased risk of renal cell cancer (RCC) in several studies, but not in all studies. Mutations in the von Hippel-Lindau (VHL) gene are associated with the clear-cell type of sporadic RCC. We investigated whether alcohol intake is associated with mutations in the VHL-gene in sporadic RCC. In 1986 the Netherlands Cohort Study on Diet and Cancer was initiated. 120,852 men and women, aged 55 to 69 years of age, completed a self-administered questionnaire at baseline on dietary habits and other risk factors for cancer. Data were processed and analyzed using the case-cohort approach, enumerating the cases for the entire cohort, and estimating the person years at risk in the cohort using a subcohort. Follow-up for cancer was established by record linkage with the Netherlands Cancer Registry and the nationwide pathology registry. After 11.3 years of follow-up, 314 incident cases of renal cell cancer and 4511 subcohort members (with complete data on alcohol intake) were available for analysis. Paraffin-embedded tumor tissue samples could be collected for 219 renal cell cancer patients from more than 51 pathology laboratories. One pathologist (CAHK) classified all tumor samples morphologically. DNA from malignant tissue was isolated for VHL analysis. Samples were analyzed by SSCP, followed by direct sequencing when aberrant SSCP signals were detected. Rate ratios (RRs) and corresponding 95% confidence intervals (95% CI) for RCC, VHL mutated clear-cell RCC and wild type VHL clear-cell RCC were estimated using Cox proportional hazard models. Multivariate RRs were adjusted for sex, age and cigarette smoking. BMI and energy intake did not change RRs and were not adjusted for in multivariate models. In multivariate analysis, the RRs of RCC for cohort members who consumed up to 5, 15, 30 and >30 grams of alcohol per day were 0.72, 0.64, 0.81 and 0.69 respectively compared to non-drinkers (95% CI for the >30 category, 0.44-1.07). The p for trend was 0.17. RRs were not different for clear-cell RCC with and without VHL mutations. Alcohol intake from beer, wine and liquor were associated with decreased risks of RCC in most categories, although not statistically significant. Alcohol intake from beer, however, was associated with an increased risk of clear-cell RCC without VHL mutations, the RRs for cohort members who consumed up to 5, 15 and >15 grams of alcohol from beer were 1.78 (95% CI, 0.85-3.73), 3.44 (95% CI, 1.64-7.22) and 1.25 (95% CI, 0.29-5.75) respectively compared to non drinkers of beer. The p for trend was 0.01. These data suggest that alcohol intake is associated with non-significantly decreased risks of RCC. Intake of beer is associated with an increased risk of wild type VHL clear-cell RCC. False-positive findings because of multiple testing and small numbers cannot be excluded, and further research is needed.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]