Lipoprotein and metabolite associations to breast cancer risk in the HUNT2 study

Debik, Julia; Schäfer, Hartmut; Andreassen, Trygve; Wang, Rui; Fang, Fang; Cannet, Claire; Spraul, Manfred; Bathen, Tone Frost; Giskeødegård, Guro F.

doi:10.1038/s41416-022-01924-1

Cited by 8 publications

(19 citation statements)

References 51 publications

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“…We observed that differences in serum lipid concentrations between BC cases and controls were more frequent in the subgroup of younger women (below 45 years old), which were putatively pre-menopausal (actual menopause status was missing for the majority of study participants). Hence, this observation was coherent with our previous results of the NMR-based metabolomics study performed in the cohort of HUNT2 study participants ( 17 ). In that study, the inverse correlation between the level of several VLDL subfractions and triglycerides (total serum level and HDL4 TG) and the long-term risk of breast cancer was observed for pre-menopausal women (actual status or age below 51 years).…”

Section: Resultssupporting

confidence: 92%

“…This allowed us to search for components putatively associated with a risk of breast cancer. This work has a similar design to a few other studies performed recently using different analytical platforms and targeting different cohorts ( 10 – 17 , 23 , 24 ). A strong correlation between serum metabolite concentrations and participants’ age was observed in our study, which putatively reflected the adaptation of energy and lipid metabolism due to age-related changes in hormonal balance.…”

Section: Discussionmentioning

confidence: 96%

“…Similar to the MS-based studies mentioned above, NMR-based profiling of plasma in the French SU.VI.MAX cohort revealed that women with lower levels of glycerol-derived compounds, unsaturated lipids, and lipoproteins, had a higher risk of developing breast cancer ( 10 ). Another NMR-based profiling of pre-diagnostic serum samples was performed more recently by our group in the large group of the HUNT2 study participants (1199 case-control pairs), which revealed the inverse association of breast cancer risk with several subfractions of VLDL particles (as well as TG-containing HDL particles) specifically in the subgroup of premenopausal women ( 17 ). Using the same set of samples, we searched for correlations between levels of lipid species (analyzed here by MS) and lipoprotein particles (analyzed previously by NMR).…”

Section: Discussionmentioning

confidence: 99%

“…The matching of the HUNT2 participants to the Norwegian Cancer Registry performed in 2019 allowed the identification of 1208 women who developed breast cancer within a 22-year follow-up period (the average time to cancer diagnosis was 11.7 years). For each breast cancer case (BC), a participant that remained breast cancer-free during the whole follow-up was randomly selected as a control (Ctr), matched for age at inclusion into HUNT2 ( 17 ). For the current analysis, the above set was first split into subgroups of women who were diagnosed with breast cancer during follow-up within one-year intervals after inclusion (together with their matched controls), then 30 (or 31) case-control pairs were randomly chosen from each one-year interval from 0-1 year to 14-15 years.…”

Section: Methodsmentioning

confidence: 99%

“…Recently, our group published the results of a study on risk assessment of breast cancer in the Norwegian population of women using an NMR-based metabolomics approach ( 17 ). The serum metabolites and lipids analysis included a large cohort of healthy women (more than 2400 individuals) from the Norwegian Trøndelag Health Study (HUNT2 study).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2023

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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 Trøndelag 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.

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Section: Resultssupporting

confidence: 92%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2023

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Metabolomic landscape of overall and common cancers in the UK Biobank: A prospective cohort study

Hu,

Fan,

Lin

et al. 2024

Intl Journal of Cancer

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Information about the NMR metabolomics landscape of overall, and common cancers is still limited. Based on a cohort of 83,290 participants from the UK Biobank, we used multivariate Cox regression to assess the associations between each of the 168 metabolites with the risks of overall cancer and 20 specific types of cancer. Then, we applied LASSO to identify important metabolites for overall cancer risk and obtained their associations using multivariate cox regression. We further conducted mediation analysis to evaluate the mediated role of metabolites in the effects of traditional factors on overall cancer risk. Finally, we included the 13 identified metabolites as predictors in prediction models, and compared the accuracies of our traditional models. We found that there were commonalities among the metabolic profiles of overall and specific types of cancer: the top 20 frequently identified metabolites for 20 specific types of cancer were all associated with overall cancer; most of the specific types of cancer had common identified metabolites. Meanwhile, the associations between the same metabolite with different types of cancer can vary based on the site of origin. We identified 13 metabolic biomarkers associated with overall cancer, and found that they mediated the effects of traditional factors. The accuracies of prediction models improved when we added 13 identified metabolites in models. This study is helpful to understand the metabolic mechanisms of overall and a wide range of cancers, and our results also indicate that NMR metabolites are potential biomarkers in cancer diagnosis and prevention.

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Nuclear magnetic resonance-determined lipoprotein profile and risk of breast cancer: a Mendelian randomization study

Xiao

et al. 2023

Breast Cancer Res Treat

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Lipoprotein and metabolite associations to breast cancer risk in the HUNT2 study

Cited by 8 publications

References 51 publications

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

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

Metabolomic landscape of overall and common cancers in the UK Biobank: A prospective cohort study

Nuclear magnetic resonance-determined lipoprotein profile and risk of breast cancer: a Mendelian randomization study

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