Metabolites and lipid species mediate the associations of adiposity in childhood and early adulthood with mammographic breast density in premenopausal women
Abstract Background Mammographic breast density (MBD), a strong predictor of breast cancer, is highly influenced by body mass index (BMI) in childhood and early adulthood, but the mechanisms underlying these associations are not fully understood. Our goal is to identify biomarkers that mediate the a...
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BMC
2025-02-01
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| Series: | Breast Cancer Research |
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| Online Access: | https://doi.org/10.1186/s13058-025-01970-6 |
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| author | Kayla R. Getz Myung Sik Jeon Lili Liu Lei Liu Haixiang Zhang Chongliang Luo Jingqin Luo Adetunji T. Toriola |
| author_facet | Kayla R. Getz Myung Sik Jeon Lili Liu Lei Liu Haixiang Zhang Chongliang Luo Jingqin Luo Adetunji T. Toriola |
| author_sort | Kayla R. Getz |
| collection | DOAJ |
| description | Abstract Background Mammographic breast density (MBD), a strong predictor of breast cancer, is highly influenced by body mass index (BMI) in childhood and early adulthood, but the mechanisms underlying these associations are not fully understood. Our goal is to identify biomarkers that mediate the associations of BMI at ages 10 and 18 with MBD in premenopausal women. Methods This study consists of 705 premenopausal women who had their screening mammogram at Washington University in St. Louis, MO, and provided a fasting blood sample. Our comprehensive metabolomic and lipidomic profiling yielded complete data for 828 metabolites and 857 lipid species after imputation. We used Volpara to determine volumetric measures of MBD. We performed high dimensional mediation analysis using the HIMA R package, adjusted for confounders, to determine whether lipid species and metabolites mediate the associations of BMI at 10 and 18 with MBD. We applied a false discovery rate (FDR) p-value < 0.1. Results Four metabolites (glutamate, β-cryptoxanthin, cortolone glucuronide (1), phytanate) significantly mediated the association of BMI at 10 with volumetric percent density (VPD), and two (glutamate, β-cryptoxanthin) mediated the association of BMI at 18 with VPD. Glutamate was the strongest mediator across time points. Glutamate mediated 6.7% (FDR p-value = 0.06) and 9.3% (FDR p-value = 0.008) of the association between BMI at age 10 and 18, respectively. Four lipid species (CER(18:0), LCER(14:0), LPC(18:1), PC(18:1/18:1)), mediated the association of BMI at 10 with VPD, while five lipid species (CER(18:0), LCER(14:0), PC(18:1/18:1), TAG56:5-FA22:5, TAG52:2-FA16:0) mediated the association of BMI at 18 with VPD. The strongest mediator was PC(18:1/18:1), which mediated 9.7%, (FDR-p = 0.009) and 7.7%, (FDR-p = 0.04) of the association of BMI at age 10 and 18 with VPD, respectively. Conclusions Metabolites in amino acid, lipid, cofactor/vitamin, and xenobiotic super-pathways as well as lipid species across the phospholipid, neutral complex lipid and sphingolipid super-pathways mediated the associations of BMI in early-life and MBD in premenopausal women. This study offers insight into the biological mechanisms underlying the link between early-life adiposity and MBD, which can support future research into breast cancer prevention. |
| format | Article |
| id | doaj-art-779ef1abadba4e7eb97365820aa0be58 |
| institution | Kabale University |
| issn | 1465-542X |
| language | English |
| publishDate | 2025-02-01 |
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| series | Breast Cancer Research |
| spelling | doaj-art-779ef1abadba4e7eb97365820aa0be582025-02-09T13:00:46ZengBMCBreast Cancer Research1465-542X2025-02-0127111210.1186/s13058-025-01970-6Metabolites and lipid species mediate the associations of adiposity in childhood and early adulthood with mammographic breast density in premenopausal womenKayla R. Getz0Myung Sik Jeon1Lili Liu2Lei Liu3Haixiang Zhang4Chongliang Luo5Jingqin Luo6Adetunji T. Toriola7Division of Public Health Sciences, Department of Surgery, Washington University School of MedicineDivision of Public Health Sciences, Department of Surgery, Washington University School of MedicineDivision of Biostatistics, Washington University School of MedicineDivision of Biostatistics, Washington University School of MedicineCenter for Applied Mathematics, Tianjin UniversityDivision of Public Health Sciences, Department of Surgery, Washington University School of MedicineDivision of Public Health Sciences, Department of Surgery, Washington University School of MedicineDivision of Public Health Sciences, Department of Surgery, Washington University School of MedicineAbstract Background Mammographic breast density (MBD), a strong predictor of breast cancer, is highly influenced by body mass index (BMI) in childhood and early adulthood, but the mechanisms underlying these associations are not fully understood. Our goal is to identify biomarkers that mediate the associations of BMI at ages 10 and 18 with MBD in premenopausal women. Methods This study consists of 705 premenopausal women who had their screening mammogram at Washington University in St. Louis, MO, and provided a fasting blood sample. Our comprehensive metabolomic and lipidomic profiling yielded complete data for 828 metabolites and 857 lipid species after imputation. We used Volpara to determine volumetric measures of MBD. We performed high dimensional mediation analysis using the HIMA R package, adjusted for confounders, to determine whether lipid species and metabolites mediate the associations of BMI at 10 and 18 with MBD. We applied a false discovery rate (FDR) p-value < 0.1. Results Four metabolites (glutamate, β-cryptoxanthin, cortolone glucuronide (1), phytanate) significantly mediated the association of BMI at 10 with volumetric percent density (VPD), and two (glutamate, β-cryptoxanthin) mediated the association of BMI at 18 with VPD. Glutamate was the strongest mediator across time points. Glutamate mediated 6.7% (FDR p-value = 0.06) and 9.3% (FDR p-value = 0.008) of the association between BMI at age 10 and 18, respectively. Four lipid species (CER(18:0), LCER(14:0), LPC(18:1), PC(18:1/18:1)), mediated the association of BMI at 10 with VPD, while five lipid species (CER(18:0), LCER(14:0), PC(18:1/18:1), TAG56:5-FA22:5, TAG52:2-FA16:0) mediated the association of BMI at 18 with VPD. The strongest mediator was PC(18:1/18:1), which mediated 9.7%, (FDR-p = 0.009) and 7.7%, (FDR-p = 0.04) of the association of BMI at age 10 and 18 with VPD, respectively. Conclusions Metabolites in amino acid, lipid, cofactor/vitamin, and xenobiotic super-pathways as well as lipid species across the phospholipid, neutral complex lipid and sphingolipid super-pathways mediated the associations of BMI in early-life and MBD in premenopausal women. This study offers insight into the biological mechanisms underlying the link between early-life adiposity and MBD, which can support future research into breast cancer prevention.https://doi.org/10.1186/s13058-025-01970-6Early-lifeAge 10Age 18Body mass indexLipidomicsMammographic breast density |
| spellingShingle | Kayla R. Getz Myung Sik Jeon Lili Liu Lei Liu Haixiang Zhang Chongliang Luo Jingqin Luo Adetunji T. Toriola Metabolites and lipid species mediate the associations of adiposity in childhood and early adulthood with mammographic breast density in premenopausal women Breast Cancer Research Early-life Age 10 Age 18 Body mass index Lipidomics Mammographic breast density |
| title | Metabolites and lipid species mediate the associations of adiposity in childhood and early adulthood with mammographic breast density in premenopausal women |
| title_full | Metabolites and lipid species mediate the associations of adiposity in childhood and early adulthood with mammographic breast density in premenopausal women |
| title_fullStr | Metabolites and lipid species mediate the associations of adiposity in childhood and early adulthood with mammographic breast density in premenopausal women |
| title_full_unstemmed | Metabolites and lipid species mediate the associations of adiposity in childhood and early adulthood with mammographic breast density in premenopausal women |
| title_short | Metabolites and lipid species mediate the associations of adiposity in childhood and early adulthood with mammographic breast density in premenopausal women |
| title_sort | metabolites and lipid species mediate the associations of adiposity in childhood and early adulthood with mammographic breast density in premenopausal women |
| topic | Early-life Age 10 Age 18 Body mass index Lipidomics Mammographic breast density |
| url | https://doi.org/10.1186/s13058-025-01970-6 |
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