Abstract A029: Metabolomic profiles among African-American and White breast cancer survivors: An exploratory comparison of correlations with body weight and body composition
Authors: Cher M Dallal, Li Feng, Charles Ma, Katherine Tkaczuk, Stephen Thomas, Joanne F. Dorgan
Journal: Cancer Research (2024)

Abstract Objective: Obesity, a strong risk and prognostic factor for postmenopausal breast cancer, is associated with numerous disruptions to the metabolome. However, it remains unclear whether obesity-metabolite associations vary when considering direct measures of adiposity versus body weight, particularly among breast cancer survivors. This analysis aims to compare correlations of body mass index (BMI) and dual-energy x-ray absorptiometry (DXA) derived measures of adiposity (percent fat, total fat) with global serum metabolites. Methods: A cross-sectional analysis was conducted among 60 postmenopausal breast cancer survivors, including 25 African-American and 35 White women within five years of their breast cancer diagnosis who were seen for care at the University of Maryland (UM) Greenebaum Comprehensive Cancer Center (Baltimore, Maryland) and the Cancer Institute at the UM St. Joseph Medical Center (Towson, Maryland). Measured height and weight were used to calculate body mass index (kg/m2); percent fat, total fat and lean mass were quantified using DXA. Global metabolomic profiling in EDTA plasma samples was performed by liquid chromatography-tandem mass spectrometry at Metabolon, Inc. Metabolites were log transformed and partial correlations of BMI, percent fat and total fat (adjusted for age, race and fasting status) were estimated. Analyses of total fat also adjusted for lean mass. The Benjamini Hochberg procedure was used to control the false discovery rate for multiple comparisons. Results: A total of 1353 metabolites, including those with known and unknown identities, were detected. After excluding metabolites with a coefficient of variation ³ 25% or with ³ 30% of values below the limit of detection, 978 metabolites remained for analyses. The median BMI among all women (n=60) was 29.7 kg/m2 ranging from 20.7-46.7 kg/m2. Percent fat ranged from 30.5 – 54.3% with a median of 41.1% while the median total fat was 27.9 kg (17.2-62.7 kg). BMI was strongly correlated with %fat (r=0.8, p=6.6e-08) and total fat after adjustment for lean mass (r=0.6, p=5.7e-05). In analyses of all women, after adjustment for age, race and fasting status, 73 metabolites correlated with BMI, 110 with percent fat and 92 with total fat adjusted for lean mass (q-value &amp;lt;.15). Of those, 27 metabolites correlated with all three metrics while 39 metabolites were distinctly correlated with BMI only, 10 with percent fat only and 21 with total fat only. BMI, percent fat and total fat were most commonly correlated with lipids and amino acids. Conclusions: Preliminary analyses suggest characterizing obesity with metrics of body composition may provide further insight into obesity-metabolite associations among breast cancer survivors. Analyses are ongoing to assess differences in correlations by race and to examine metabolite patterns via metabolite set enrichment analyses. Citation Format: Cher M Dallal, Li Feng, Charles Ma, Katherine Tkaczuk, Stephen Thomas, Joanne F. Dorgan. Metabolomic profiles among African-American and White breast cancer survivors: An exploratory comparison of correlations with body weight and body composition [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A029.