习惯性饮酒的新型生物标志物及其与胰腺癌、肝癌风险和肝脏疾病死亡率的关联。
Novel Biomarkers of Habitual Alcohol Intake and Associations With Risk of Pancreatic and Liver Cancers and Liver Disease Mortality.
机构信息
Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute,National Institutes of Health, Bethesda, MD, USA.
Nutritional Epidemiology Group, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
出版信息
J Natl Cancer Inst. 2021 Nov 2;113(11):1542-1550. doi: 10.1093/jnci/djab078.
BACKGROUND
Alcohol is an established risk factor for several cancers, but modest alcohol-cancer associations may be missed because of measurement error in self-reported assessments. Biomarkers of habitual alcohol intake may provide novel insight into the relationship between alcohol and cancer risk.
METHODS
Untargeted metabolomics was used to identify metabolites correlated with self-reported habitual alcohol intake in a discovery dataset from the European Prospective Investigation into Cancer and Nutrition (EPIC; n = 454). Statistically significant correlations were tested in independent datasets of controls from case-control studies nested within EPIC (n = 280) and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC; n = 438) study. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations of alcohol-associated metabolites and self-reported alcohol intake with risk of pancreatic cancer, hepatocellular carcinoma (HCC), liver cancer, and liver disease mortality in the contributing studies.
RESULTS
Two metabolites displayed a dose-response association with self-reported alcohol intake: 2-hydroxy-3-methylbutyric acid and an unidentified compound. A 1-SD (log2) increase in levels of 2-hydroxy-3-methylbutyric acid was associated with risk of HCC (OR = 2.54, 95% CI = 1.51 to 4.27) and pancreatic cancer (OR = 1.43, 95% CI = 1.03 to 1.99) in EPIC and liver cancer (OR = 2.00, 95% CI = 1.44 to 2.77) and liver disease mortality (OR = 2.16, 95% CI = 1.63 to 2.86) in ATBC. Conversely, a 1-SD (log2) increase in questionnaire-derived alcohol intake was not associated with HCC or pancreatic cancer in EPIC or liver cancer in ATBC but was associated with liver disease mortality (OR = 2.19, 95% CI = 1.60 to 2.98) in ATBC.
CONCLUSIONS
2-hydroxy-3-methylbutyric acid is a candidate biomarker of habitual alcohol intake that may advance the study of alcohol and cancer risk in population-based studies.
背景
酒精是多种癌症的既定风险因素，但由于自我报告评估中的测量误差，可能会错过适度的酒精与癌症关联。习惯性酒精摄入量的生物标志物可能为酒精与癌症风险之间的关系提供新的见解。
方法
在欧洲前瞻性癌症与营养研究（EPIC）中的一项发现性数据集（n=454）中，使用非靶向代谢组学来鉴定与自我报告的习惯性酒精摄入量相关的代谢物。在 EPIC 中嵌套的病例对照研究的对照独立数据集（n=280）和α-生育酚、β-胡萝卜素癌症预防（ATBC）研究（n=438）中测试了具有统计学意义的相关性。条件逻辑回归用于估计与酒精相关代谢物和自我报告的酒精摄入量与胰腺癌、肝细胞癌（HCC）、肝癌和肝脏疾病死亡率风险的关联的比值比（OR）和 95%置信区间（CI）。
结果
两种代谢物与自我报告的酒精摄入量呈剂量反应关系：2-羟基-3-甲基丁酸和一种未识别的化合物。2-羟基-3-甲基丁酸水平每增加 1-SD（log2），与 EPIC 中的 HCC（OR=2.54，95%CI=1.51 至 4.27）和胰腺癌（OR=1.43，95%CI=1.03 至 1.99）风险相关，与 ATBC 中的肝癌（OR=2.00，95%CI=1.44 至 2.77）和肝脏疾病死亡率（OR=2.16，95%CI=1.63 至 2.86）风险相关。相反，EPIC 中自我报告的酒精摄入量每增加 1-SD（log2）与 HCC 或胰腺癌无关，而与 ATBC 中的肝脏疾病死亡率相关（OR=2.19，95%CI=1.60 至 2.98）。
结论
2-羟基-3-甲基丁酸是习惯性酒精摄入量的候选生物标志物，可能会推进基于人群的研究中酒精与癌症风险的研究。
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