■血清代谢组是与乳腺癌风险相关的分子生物标志物的潜在来源。在这里,我们旨在分析从参与挪威Trøndelag健康研究(HUNT2研究)的健康女性收集的诊断前血清样本中存在的代谢物,这些女性可以获得有关发展为乳腺癌的长期信息。
选择了参与HUNT2研究的在15年随访期内发展为乳腺癌的妇女(BC病例)和年龄匹配的无乳腺癌妇女(n=453病例对照对)。使用高分辨率质谱方法对284种化合物进行了定量分析,包括30种氨基酸和生物胺,己糖,和253脂质(酰基肉碱,甘油酯,磷脂酰胆碱,鞘脂,和胆固醇酯)。
■年龄是导致数据集中巨大异质性的主要混杂因素,因此,我们分别对年龄定义的亚组进行了分析.在年轻女性(<45岁)的亚组中观察到最大数量的代谢物,其血清水平区分BC病例和对照(82种化合物)。值得注意的是,甘油酯水平增加,磷脂酰胆碱,在年轻和中年女性(≤64岁)中,鞘脂与癌症风险降低相关.另一方面,在老年女性(>64岁)中,血脂水平升高与乳腺癌风险增加相关.此外,在样本采集后早期(<5年)和晚期(>10年)的BC病例之间,可以检测到几种代谢物的血清水平不同,然而,这些化合物也与参与者的年龄相关。当前的结果与在HUNT2参与者队列中进行的基于NMR的代谢组学研究的结果一致,其中VLDL亚组分血清水平升高与绝经前女性乳腺癌风险降低相关.
■在诊断前血清样本中检测到的代谢物水平的变化,这反映了脂质和氨基酸代谢受损,以年龄依赖性方式与乳腺癌的长期风险相关。
UNASSIGNED: The serum metabolome is a potential source of molecular biomarkers associated with the risk of breast cancer. Here we aimed to analyze metabolites present in pre-diagnostic serum samples collected from healthy women participating in the Norwegian Trøndelag Health
Study (HUNT2
study) for whom long-term information about developing breast cancer was available.
UNASSIGNED: Women participating in the HUNT2
study who developed breast cancer within a 15-year follow-up period (BC cases) and age-matched women who stayed breast cancer-free were selected (n=453 case-control pairs). Using a high-resolution mass spectrometry approach 284 compounds were quantitatively analyzed, including 30 amino acids and biogenic amines, hexoses, and 253 lipids (acylcarnitines, glycerides, phosphatidylcholines, sphingolipids, and cholesteryl esters).
UNASSIGNED: Age was a major confounding factor responsible for a large heterogeneity in the dataset, hence age-defined subgroups were analyzed separately. The largest number of metabolites whose serum levels differentiated BC cases and controls (82 compounds) were observed in the subgroup of younger women (<45 years old). Noteworthy, increased levels of glycerides, phosphatidylcholines, and sphingolipids were associated with reduced risk of cancer in younger and middle-aged women (≤64 years old). On the other hand, increased levels of serum lipids were associated with an enhanced risk of breast cancer in older women (>64 years old). Moreover, several metabolites could be detected whose serum levels were different between BC cases diagnosed earlier (<5 years) and later (>10 years) after sample collecting, yet these compounds were also correlated with the age of participants. Current results were coherent with the results of the NMR-based metabolomics
study performed in the cohort of HUNT2 participants, where increased serum levels of VLDL subfractions were associated with reduced risk of breast cancer in premenopausal women.
UNASSIGNED: Changes in metabolite levels detected in pre-diagnostic serum samples, which reflected an impaired lipid and amino acid metabolism, were associated with long-term risk of breast cancer in an age-dependent manner.