Department of Preventive Medicine, Chonnam National University Medical School, Hwasun, Korea.
Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Korea.
Cancer Res Treat. 2021 Jul;53(3):754-762. doi: 10.4143/crt.2020.478. Epub 2020 Dec 24.
Excessive alcohol consumption has been linked to an increased risk of colorectal cancer (CRC). We evaluated the association between alcohol-related genetic variants and CRC risk.
The study cohort consisted of 5,435 CRC cases and 3,553 population-based cancer-free controls. Genotype data were generated from germline DNA using the Infinium OncoArray-500K BeadChip in 2,535 cases and 2,287 controls and the Infinium Multi-Ethnic Global BeadChip in 2,900 cases and 1,266 controls. The associations between aldehyde dehydrogenase 2 (ALDH2) rs671 and alcohol dehydrogenase 1B (ADH1B) rs1229984 polymorphisms and CRC risk were assessed using multivariate logistic regression analyses.
Compared with the major homozygous ALDH2 genotype (GG), heterozygous or minor homozygous ALDH2 genotype (GA or AA, related to a low alcohol consumption) was significantly associated with a reduced risk for CRC in men (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.68 to 0.90), but not in women (OR, 0.70; 95% CI, 0.47 to 1.05). A stronger association was found among regular drinkers (OR, 0.58; 95% CI, 0.47 to 0.71 in men and OR, 0.33; 95% CI, 0.18 to 0.58 in women). No association of CRC risk with ADH1B rs1229984 genotype was found. The association between alcohol-related combined genotypes and risk of CRC was significant (p for linear=0.001). The combined genotype with the highest genetically predicted alcohol consumption (ALDH2 rs671 GG and ADH1B rs1229984 AG/GG) was associated with a high risk for CRC (OR, 1.35; 95% CI, 1.11 to 1.63).
Our study provides strong evidence for a possible causal association between alcohol consumption and CRC risk.
过量饮酒与结直肠癌（CRC）风险增加有关。我们评估了与酒精相关的遗传变异与 CRC 风险之间的关联。
研究队列包括 5435 例 CRC 病例和 3553 例基于人群的无癌症对照。使用 Infinium OncoArray-500K BeadChip 在 2535 例病例和 2287 例对照中以及 Infinium Multi-Ethnic Global BeadChip 在 2900 例病例和 1266 例对照中生成来自种系 DNA 的基因型数据。使用多变量逻辑回归分析评估乙醛脱氢酶 2（ALDH2）rs671 和醇脱氢酶 1B（ADH1B）rs1229984 多态性与 CRC 风险之间的关联。
与主要纯合 ALDH2 基因型（GG）相比，杂合或次要纯合 ALDH2 基因型（GA 或 AA，与低酒精摄入相关）与男性 CRC 风险降低显著相关（比值比 [OR]，0.78；95%置信区间 [CI]，0.68 至 0.90），但在女性中无显著相关性（OR，0.70；95%CI，0.47 至 1.05）。在经常饮酒者中发现了更强的相关性（OR，0.58；95%CI，男性 0.47 至 0.71 和女性 0.33；95%CI，0.18 至 0.58）。未发现 CRC 风险与 ADH1B rs1229984 基因型相关。与酒精相关的组合基因型与 CRC 风险之间存在显著关联（p 值线性=0.001）。具有最高遗传预测饮酒量的组合基因型（ALDH2 rs671 GG 和 ADH1B rs1229984 AG/GG）与 CRC 风险增加相关（OR，1.35；95%CI，1.11 至 1.63）。
本研究为酒精摄入与 CRC 风险之间可能存在因果关系提供了有力证据。
