Alcohol consumption and serum metabolite concentrations in young women
Alcohol consumption and serum metabolite concentrations in young women
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DOI：
10.1007/s10552-019-01256-1
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发表时间：
2020-02-01
影响因子：
2.3
通讯作者：
Van Horn, Linda
中科院分区：
文献类型：
--
作者：
Dorgan, Joanne F.;Jung, Seungyoun;Van Horn, Linda
目的 饮酒是乳腺癌的一个确定的危险因素，尽管需要进一步的研究来加深我们对这种关联机制的理解。我们使用全局代谢组学分析来识别可能介导酒精与乳腺癌关联的血清代谢物和代谢途径。方法 对参加 2006 年儿童膳食干预研究随访研究 (DISC06) 的 211 名 25-29 岁健康女性报告的饮酒量和血清代谢物浓度进行横断面分析。使用多变量线性混合效应回归评估酒精-代谢物关联。结果 在调整饮食成分和其他潜在混杂因素后，酒精与多种血清代谢物显着相关（FDR p < 0.05）。氨基酸肌氨酸、omega-3 脂肪酸二十碳五烯酸酯和类固醇 4-androsten-3beta,17beta-diol monosulfate 与酒精摄入量呈正相关，而 γ-生育酚代谢物 γ-羧乙基羟基色满 (CEHC) 则呈负相关。酒精与 2- 柠檬酸甲酯和 4-androsten-3beta,17beta-diol disulfate 呈显着正相关（FDR p < 0.10）。代谢物集富集分析发现，类固醇和甘氨酸途径中与饮酒相关的成员比偶然预期的要多。结论 当前分析中大多数与酒精相关的代谢物参与了介导酒精与乳腺癌关联的假设途径，包括激素、一碳代谢和氧化应激途径，但它们也可能通过其他途径影响风险。需要对酒精代谢物关联进行独立复制，并对已确认的与乳腺癌风险的关联进行前瞻性评估。
Purpose Alcohol consumption is an established breast cancer risk factor, though further research is needed to advance our understanding of the mechanism underlying the association. We used global metabolomics profiling to identify serum metabolites and metabolic pathways that could potentially mediate the alcohol-breast cancer association. Methods A cross-sectional analysis of reported alcohol consumption and serum metabolite concentrations was conducted among 211 healthy women 25-29 years old who participated in the Dietary Intervention Study in Children 2006 Follow-Up Study (DISC06). Alcohol-metabolite associations were evaluated using multivariable linear mixed-effects regression. Results Alcohol was significantly (FDR p < 0.05) associated with several serum metabolites after adjustment for diet composition and other potential confounders. The amino acid sarcosine, the omega-3 fatty acid eicosapentaenoate, and the steroid 4-androsten-3beta,17beta-diol monosulfate were positively associated with alcohol intake, while the gamma-tocopherol metabolite gamma-carboxyethyl hydroxychroman (CEHC) was inversely associated. Positive associations of alcohol with 2-methylcitrate and 4-androsten-3beta,17beta-diol disulfate were borderline significant (FDR p < 0.10). Metabolite set enrichment analysis identified steroids and the glycine pathway as having more members associated with alcohol consumption than expected by chance. Conclusions Most of the metabolites associated with alcohol in the current analysis participate in pathways hypothesized to mediate the alcohol-breast cancer association including hormonal, one-carbon metabolism, and oxidative stress pathways, but they could also affect risk via alternative pathways. Independent replication of alcohol-metabolite associations and prospective evaluation of confirmed associations with breast cancer risk are needed.