Childhood adiposity, serum metabolites and breast density in young women
Abstract Background Childhood adiposity is inversely associated with young adult percent dense breast volume (%DBV) and absolute dense breast volume (ADBV), which could contribute to its protective effect for breast cancer later in life. The objective of this study was to identify metabolites in chi...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | Breast Cancer Research |
| Online Access: | https://doi.org/10.1186/s13058-022-01588-y |
| _version_ | 1797977210742636544 |
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| author | Joanne F. Dorgan Heather J. Baer Kimberly A. Bertrand Erin S. LeBlanc Seungyoun Jung Laurence S. Magder Linda G. Snetselaar Victor J. Stevens Yuji Zhang Linda Van Horn |
| author_facet | Joanne F. Dorgan Heather J. Baer Kimberly A. Bertrand Erin S. LeBlanc Seungyoun Jung Laurence S. Magder Linda G. Snetselaar Victor J. Stevens Yuji Zhang Linda Van Horn |
| author_sort | Joanne F. Dorgan |
| collection | DOAJ |
| description | Abstract Background Childhood adiposity is inversely associated with young adult percent dense breast volume (%DBV) and absolute dense breast volume (ADBV), which could contribute to its protective effect for breast cancer later in life. The objective of this study was to identify metabolites in childhood serum that may mediate the inverse association between childhood adiposity and young adult breast density. Methods Longitudinal data from 182 female participants in the Dietary Intervention Study in Children (DISC) and the DISC 2006 (DISC06) Follow-Up Study were analyzed. Childhood adiposity was assessed by anthropometry at the DISC visit with serum available that occurred closest to menarche and expressed as a body mass index (BMI) z-score. Serum metabolites were measured by untargeted metabolomics using ultra-high-performance liquid chromatography–tandem mass spectrometry. %DBV and ADBV were measured by magnetic resonance imaging at the DISC06 visit when participants were 25–29 years old. Robust mixed effects linear regression was used to identify serum metabolites associated with childhood BMI z-scores and breast density, and the R package mediation was used to quantify mediation. Results Of the 115 metabolites associated with BMI z-scores (FDR < 0.20), 4 were significantly associated with %DBV and 6 with ADBV before, though not after, adjustment for multiple comparisons. Mediation analysis identified 2 unnamed metabolites, X-16576 and X-24588, as potential mediators of the inverse association between childhood adiposity and dense breast volume. X-16576 mediated 14% (95% confidence interval (CI) = 0.002, 0.46; P = 0.04) of the association of childhood adiposity with %DBV and 11% (95% CI = 0.01, 0.26; P = 0.02) of its association with ADBV. X-24588 also mediated 7% (95% CI = 0.001, 0.18; P = 0.05) of the association of childhood adiposity with ADBV. None of the other metabolites examined contributed to mediation of the childhood adiposity–%DBV association, though there was some support for contributions of lysine, valine and 7-methylguanine to mediation of the inverse association of childhood adiposity with ADBV. Conclusions Additional large longitudinal studies are needed to identify metabolites and other biomarkers that mediate the inverse association of childhood adiposity with breast density and possibly breast cancer risk. |
| first_indexed | 2024-04-11T05:03:20Z |
| format | Article |
| id | doaj.art-9eed5e334011455c98c416ae83c14db8 |
| institution | Directory Open Access Journal |
| issn | 1465-542X |
| language | English |
| last_indexed | 2024-04-11T05:03:20Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj.art-9eed5e334011455c98c416ae83c14db82022-12-25T12:34:43ZengBMCBreast Cancer Research1465-542X2022-12-0124111110.1186/s13058-022-01588-yChildhood adiposity, serum metabolites and breast density in young womenJoanne F. Dorgan0Heather J. Baer1Kimberly A. Bertrand2Erin S. LeBlanc3Seungyoun Jung4Laurence S. Magder5Linda G. Snetselaar6Victor J. Stevens7Yuji Zhang8Linda Van Horn9Division of Cancer Epidemiology, Department of Epidemiology and Public Health, University of Maryland School of MedicineDepartment of Epidemiology, Harvard T.H. Chan School of Public HealthSlone Epidemiology Center, Boston University School of MedicineKaiser Permanente Center for Health ResearchDepartment of Nutritional Science and Food Management, Ewha Womans UniversityDivision of Cancer Epidemiology, Department of Epidemiology and Public Health, University of Maryland School of MedicineDepartment of Epidemiology, University of Iowa College of Public HealthKaiser Permanente Center for Health ResearchDepartment of Epidemiology and Public Health, University of Maryland School of MedicineDepartment of Preventive Medicine, Northwestern University Feinberg School of MedicineAbstract Background Childhood adiposity is inversely associated with young adult percent dense breast volume (%DBV) and absolute dense breast volume (ADBV), which could contribute to its protective effect for breast cancer later in life. The objective of this study was to identify metabolites in childhood serum that may mediate the inverse association between childhood adiposity and young adult breast density. Methods Longitudinal data from 182 female participants in the Dietary Intervention Study in Children (DISC) and the DISC 2006 (DISC06) Follow-Up Study were analyzed. Childhood adiposity was assessed by anthropometry at the DISC visit with serum available that occurred closest to menarche and expressed as a body mass index (BMI) z-score. Serum metabolites were measured by untargeted metabolomics using ultra-high-performance liquid chromatography–tandem mass spectrometry. %DBV and ADBV were measured by magnetic resonance imaging at the DISC06 visit when participants were 25–29 years old. Robust mixed effects linear regression was used to identify serum metabolites associated with childhood BMI z-scores and breast density, and the R package mediation was used to quantify mediation. Results Of the 115 metabolites associated with BMI z-scores (FDR < 0.20), 4 were significantly associated with %DBV and 6 with ADBV before, though not after, adjustment for multiple comparisons. Mediation analysis identified 2 unnamed metabolites, X-16576 and X-24588, as potential mediators of the inverse association between childhood adiposity and dense breast volume. X-16576 mediated 14% (95% confidence interval (CI) = 0.002, 0.46; P = 0.04) of the association of childhood adiposity with %DBV and 11% (95% CI = 0.01, 0.26; P = 0.02) of its association with ADBV. X-24588 also mediated 7% (95% CI = 0.001, 0.18; P = 0.05) of the association of childhood adiposity with ADBV. None of the other metabolites examined contributed to mediation of the childhood adiposity–%DBV association, though there was some support for contributions of lysine, valine and 7-methylguanine to mediation of the inverse association of childhood adiposity with ADBV. Conclusions Additional large longitudinal studies are needed to identify metabolites and other biomarkers that mediate the inverse association of childhood adiposity with breast density and possibly breast cancer risk.https://doi.org/10.1186/s13058-022-01588-y |
| spellingShingle | Joanne F. Dorgan Heather J. Baer Kimberly A. Bertrand Erin S. LeBlanc Seungyoun Jung Laurence S. Magder Linda G. Snetselaar Victor J. Stevens Yuji Zhang Linda Van Horn Childhood adiposity, serum metabolites and breast density in young women Breast Cancer Research |
| title | Childhood adiposity, serum metabolites and breast density in young women |
| title_full | Childhood adiposity, serum metabolites and breast density in young women |
| title_fullStr | Childhood adiposity, serum metabolites and breast density in young women |
| title_full_unstemmed | Childhood adiposity, serum metabolites and breast density in young women |
| title_short | Childhood adiposity, serum metabolites and breast density in young women |
| title_sort | childhood adiposity serum metabolites and breast density in young women |
| url | https://doi.org/10.1186/s13058-022-01588-y |
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