Abstract A033: Metabolomics reveals racial differences in metabolites among women

Abstract Background: Non-Hispanic Black (NHB) women experience disparities in cancer outcomes and mortality compared with non-Hispanic White (NHW) women. While social determinants of health contribute to these differences, investigating potential biological factors behind the observed racial differences is essential for developing effective health interventions. Therefore, we performed a comprehensive analysis comparing the metabolomic profiles of NHB and NHW women to identify whether differences exist in metabolites. Methods: We performed metabolomic profiling on 674 women recruited at Washington University School of Medicine, St. Louis, MO. A total of 1074 metabolites were profiled at Metabolon. We excluded 246 metabolites with missing values in ≥300 women from the analyses. We used the 10-nearest neighbor method for imputing missing data. We investigated the associations between metabolites and race using linear regression models, adjusting for age, body mass index, alcohol consumption, and education level. Metabolites were log-transformed before regression analyses, and linear coefficients were back-transformed to the original scale. A Bonferroni-adjusted p-value10-5 was considered statistically significant. Pathway enrichment analyses were conducted for differential metabolites within each super-pathway. Results: Twenty-five (3.0%) of the 828 metabolites differed significantly between NHW and NHB women at the Bonferroni-adjusted p- value10-5 level, with 19 metabolites higher in NHW women and 6 metabolites higher in NHB women. These metabolites belong to amino acid (n=12), xenobiotics (n=9), lipid (n=2), cofactors and vitamins (n=1), and partially characterized molecules (n=1) super-pathways. In NHB women, the top 3 metabolites with the highest percentage differences compared with NHW women were 2-naphthol sulfate (89.7%, p=3.6×10-6)chemical, 2-hydroxyfluorene sulfate (71.6%, p=5.9×10-8)tobacco metabolite, and carotene diol (3) (35.6%, p=1.1×10-6)vitamin A metabolism. Conversely, the top 3 metabolites with the highest percentage differences in NHW women compared with NHB women were N6-methyllysine (59.0%, p=1.2×10-26)lysine metabolism, tryptophan betaine (57.7%, p=2.1×10-11)tryptophan metabolism, and theophylline (52.8%, p=2.2×10-7)xanthine metabolism. Conclusions: We identified racial differences in several functional metabolites among women that may contribute to the observed cancer disparities and have implications for cancer prevention. Citation Format: Ghazaleh Pourali, Liang Li, Kayla R. Getz, Myung Sik Jeon, Jingqin Luo, Chongliang Luo, Adetunji T. Toriola. Metabolomics reveals racial differences in metabolites among women abstract. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A033.