GROW - School for Oncology and Developmental Biology, Department of Epidemiology, Maastricht University, The Netherlands.
Alcohol. 2011 May;45(3):217-25. doi: 10.1016/j.alcohol.2010.10.003. Epub 2010 Dec 15.
Within the Netherlands Cohort Study (1986), we examined associations between alcohol consumption, the alcohol dehydrogenase 1C (ADH1C) genotype, and risk of colorectal cancer (CRC). After a follow-up period of 7.3 years, 594 CRC cases with information on genotype and baseline alcohol intake were available for analyses. Adjusted incidence rate ratios (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. In subjects who reported to have consumed equal amounts of total alcohol both 5 years before baseline and at baseline, drinkers of ≥30g of alcohol per day with the ADH1C*2/2 genotype were associated-although not statistically significant-with an increased risk of CRC relative to abstainers with the ADH1C1/1 genotype (RR: 1.91, 95% CI: 0.68, 5.34). The risk estimate in this exposure group increased slightly when compared with light drinkers of ≥0.5-<5g/day with the ADH1C*1/*1 genotype (RR: 2.32, 95% CI: 0.80, 6.72). The interaction term however, was not statistically significant (P>.05). In subjects who reported to have consumed equal amounts of total alcohol both 5 years before baseline and at baseline, drinkers of ≥30g of alcohol per day were associated-although not statistically significant-with an increased risk of CRC relative to abstainers (RR: 1.38, 95% CI: 0.80, 2.38). This risk estimate for high-level drinkers became stronger when compared with light drinkers (RR: 1.74, 95% CI: 1.01, 2.99). As main effect of genotype, we observed that the ADH1C2/2 genotype was associated with a 42% increase in risk of CRC when compared with the ADH1C1/*1 genotype. In conclusion, both genotype and alcohol consumption were associated with an increased risk of CRC. Owing to limited statistical power, we found no apparent evidence for the ADH1C genotype as effect modifier of the relationship between alcohol intake and CRC. Nevertheless, the interaction deserves further investigation in larger genetic epidemiologic studies.
在荷兰队列研究（1986 年）中，我们研究了饮酒量、乙醛脱氢酶 1C（ADH1C）基因型与结直肠癌（CRC）风险之间的关系。经过 7.3 年的随访，有 594 例 CRC 病例提供了基因型和基线饮酒量的信息，可供分析。使用 Cox 比例风险模型估计调整后的发病率比（RR）和 95%置信区间（CI）。在报告在基线前 5 年和基线时摄入等量总酒精的受试者中，与 ADH1C*1/1 基因型的不饮酒者相比，每天摄入≥30g 酒精且携带 ADH1C2/2 基因型的饮酒者CRC 的风险呈上升趋势，但无统计学意义（RR：1.91，95%CI：0.68，5.34）。与 ADH1C1/1 基因型的每天摄入≥0.5-<5g 酒精的轻度饮酒者相比，该暴露组的风险估计略有增加（RR：2.32，95%CI：0.80，6.72）。然而，交互项无统计学意义（P>.05）。在报告在基线前 5 年和基线时摄入等量总酒精的受试者中，与不饮酒者相比，每天摄入≥30g 酒精的饮酒者CRC 的风险呈上升趋势，但无统计学意义（RR：1.38，95%CI：0.80，2.38）。与轻度饮酒者相比，该高水平饮酒者的风险估计更强（RR：1.74，95%CI：1.01，2.99）。作为基因型的主要作用，我们观察到与 ADH1C1/1 基因型相比，ADH1C2/*2 基因型使 CRC 的风险增加 42%。总之，基因型和饮酒量均与 CRC 风险增加有关。由于统计能力有限，我们没有发现 ADH1C 基因型作为饮酒与 CRC 之间关系的效应修饰因子的明显证据。然而，这种相互作用值得在更大的遗传流行病学研究中进一步探讨。
