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在一项前瞻性代谢组学研究中,血浆中溶血磷脂酰胆碱18:0水平较高与常见癌症风险较低相关。

Higher plasma levels of lysophosphatidylcholine 18:0 are related to a lower risk of common cancers in a prospective metabolomics study.

作者信息

Kühn Tilman, Floegel Anna, Sookthai Disorn, Johnson Theron, Rolle-Kampczyk Ulrike, Otto Wolfgang, von Bergen Martin, Boeing Heiner, Kaaks Rudolf

机构信息

Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120, Heidelberg, Germany.

Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114, D-14558, Nuthetal, Germany.

出版信息

BMC Med. 2016 Jan 28;14:13. doi: 10.1186/s12916-016-0552-3.

Abstract

BACKGROUND

First metabolomics studies have indicated that metabolic fingerprints from accessible tissues might be useful to better understand the etiological links between metabolism and cancer. However, there is still a lack of prospective metabolomics studies on pre-diagnostic metabolic alterations and cancer risk.

METHODS

Associations between pre-diagnostic levels of 120 circulating metabolites (acylcarnitines, amino acids, biogenic amines, phosphatidylcholines, sphingolipids, and hexoses) and the risks of breast, prostate, and colorectal cancer were evaluated by Cox regression analyses using data of a prospective case-cohort study including 835 incident cancer cases.

RESULTS

The median follow-up duration was 8.3 years among non-cases and 6.5 years among incident cases of cancer. Higher levels of lysophosphatidylcholines (lysoPCs), and especially lysoPC a C18:0, were consistently related to lower risks of breast, prostate, and colorectal cancer, independent of background factors. In contrast, higher levels of phosphatidylcholine PC ae C30:0 were associated with increased cancer risk. There was no heterogeneity in the observed associations by lag time between blood draw and cancer diagnosis.

CONCLUSION

Changes in blood lipid composition precede the diagnosis of common malignancies by several years. Considering the consistency of the present results across three cancer types the observed alterations point to a global metabolic shift in phosphatidylcholine metabolism that may drive tumorigenesis.

摘要

背景

首批代谢组学研究表明,来自可获取组织的代谢指纹图谱可能有助于更好地理解代谢与癌症之间的病因学联系。然而,目前仍缺乏关于诊断前代谢改变与癌症风险的前瞻性代谢组学研究。

方法

通过Cox回归分析,利用一项前瞻性病例队列研究的数据,评估了120种循环代谢物(酰基肉碱、氨基酸、生物胺、磷脂酰胆碱、鞘脂和己糖)的诊断前水平与乳腺癌、前列腺癌和结直肠癌风险之间的关联,该研究包括835例新发癌症病例。

结果

非癌症病例的中位随访时间为8.3年,癌症新发病例的中位随访时间为6.5年。溶血磷脂酰胆碱(lysoPCs)水平升高,尤其是lysoPC a C18:0,与乳腺癌、前列腺癌和结直肠癌的较低风险持续相关,且不受背景因素影响。相比之下,磷脂酰胆碱PC ae C30:0水平升高与癌症风险增加相关。采血与癌症诊断之间的滞后时间对观察到的关联没有异质性影响。

结论

血脂成分的变化在常见恶性肿瘤诊断前数年就已出现。考虑到本研究结果在三种癌症类型中的一致性,观察到的改变表明磷脂酰胆碱代谢存在整体代谢转变,这可能驱动肿瘤发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcd8/4730724/b7495cc4c89a/12916_2016_552_Fig1_HTML.jpg

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