Association of serum metabolome profile with the risk of breast cancer in participants of the HUNT2 study

BackgroundThe 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 Trondelag Health Study (HUNT2 study) for whom long-term information about developing breast cancer was available. MethodsWomen 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). ResultsAge 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. ConclusionsChanges 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.

Automated summary

In this study, metabolites present in pre-diagnostic serum samples from the Norwegian Trondelag Health Study were analyzed to identify biomarkers associated with the risk of breast cancer. The results showed that the levels of glycerides, phosphatidylcholines, and sphingolipids in serum were associated with a reduced risk of breast cancer in younger and middle-aged women, while increased levels of serum lipids were associated with an enhanced risk in older women. Additionally, metabolite levels were also found to be correlated with the time of sample collection and age. These findings suggest that changes in metabolite levels are associated with the long-term risk of breast cancer in an age-dependent manner.