Schouten Leo J, van Dijk Boukje A C, Oosterwijk Egbert, van Engeland Manon, Hulsbergen-van de Kaa Christina A, Kiemeney Lambertus A L M, Goldbohm Royle Alexandra, Kester Arnold, de Vogel Stefan, Schalken Jack A, van den Brandt Piet A
Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, the Netherlands.
Cancer Epidemiol Biomarkers Prev. 2008 Dec;17(12):3543-50. doi: 10.1158/1055-9965.EPI-08-0321.
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.
多项研究表明，饮酒与肾细胞癌风险降低有关。我们调查了酒精是否与肾细胞癌中冯·希佩尔-林道（VHL）基因的（表观）遗传变化有关。荷兰饮食与癌症队列研究（NLCS）始于1986年（n = 120,852），采用病例-队列研究方法。经过11.3年的随访，有314例肾细胞癌病例和4511名队列成员可供分析。从235例病例的石蜡包埋肿瘤组织中提取DNA。通过测序分析VHL突变，使用甲基化特异性PCR分析VHL启动子甲基化。在多变量分析中，与不饮酒者相比，每天饮酒量分别达到5克、15克、30克和≥30克的队列成员患肾细胞癌的风险比分别为0.72、0.64、0.81和0.69[≥30克组的95%置信区间（95%CI）为0.44 - 1.07；趋势P值为0.17]。啤酒、葡萄酒和烈酒的酒精摄入量与肾细胞癌风险降低有关，尽管无统计学意义。有或无VHL突变的透明细胞肾细胞癌的风险比无差异，但啤酒中的酒精与无VHL突变的透明细胞肾细胞癌风险增加有关（与不饮酒者相比，每天饮用≥5克啤酒的风险比为2.74；95%CI为1.35 - 5.57）。酒精与无VHL基因启动子甲基化的透明细胞肾细胞癌风险降低有关（与不饮酒者相比，每天饮用>15克酒精的风险比为0.58；95%CI为0.34 - 0.99）。在本研究中，观察到酒精与肾细胞癌之间存在无统计学意义的负相关。VHL突变或甲基化状态无统计学显著异质性。
