Abstract 2140: Untargeted lipidomics reveals racial differences in lipid species among women

Abstract Introduction: Lipids are important for many cellular processes and have been implicated in cancer development. Adopting a lipidomic approach has revealed sex-specific differences in lipid species but whether there are racial differences in lipid profiles remain unexplored. As a result, we investigated differences in lipid species between Non-Hispanic Black (NHB) vs Non-Hispanic White (NHW) women. Methods: We performed lipidomic profiling on 705 premenopausal women who were recruited during their annual screening mammogram at Washington University School of Medicine, St. Louis, MO. A total of 982 lipid species were profiled at Metabolon (Durham, NC®). 125 lipid species missing in 300 or more women were excluded from the analysis. For the remaining missing values, we employed the nearest neighbor method for imputation. We investigated the race-differentiating lipid species concentrations using linear regression models, adjusting for age and body mass index (BMI). To satisfy the assumptions of normality and homoscedasticity, we log-transformed the lipid concentrations before performing regression analyses. The linear regression coefficients were then back-transformed as percentage differences. We accounted for multiple testings by applying the Bonferroni correction. Statistical significance was defined as a Bonferroni-adjusted p-value < 10−5. Pathway enrichment analyses was conducted for differential lipid species for each sub pathway. Results: Of the 705 women, 506 were NHW and 163 were NHB. In analysis adjusted for age and BMI, 278 lipid species were significantly lower in NHB, and one lipid specie (TAG58:10-FA20:4) was higher in NHB. These species belonged to triacylglycerols (TAG, n=213), phosphatidylcholines (PC, n=25), diacylglycerols (DAG, n=22), cholesteryl esters (CE, n=4), phosphatidylethanolamines (PE, n=4), lysophosphatidylcholines (LPC, n=3), lysophosphatidylethanolamines (LPE, n=3), sphingomyelins (SM, n=2), ceramides (CER, n=1), lactosylceramides (LCER, n=1) and phosphatidylinositols (PI, n=1) sub-pathways. The TAG sub-pathway was enriched with differential lipid species (213 significant out of 518 species, p = 1.26 × 10−11). Forty-three lipid species (42 TAGs and one DAG) exhibited an absolute percentage difference > 50% between NHB and NHW women. The top 3 TAG species with the largest absolute percentage differences were TAG44:0-FA14:0 (60.6% lower in NHB women, p = 6.25 × 10−8), TAG46:2-FA16:1 (59.8% lower in NHB women, p = 1.11 × 10−14) and TAG47:2-FA16:1 (59.4% lower in NHB women, p = 8.66 × 10−20). Conversely, TAG58:10-FA20:4 was 47.1% (p = 5.79 × 10−8) higher in NHB women. Conclusions: Our study reveals novel substantial racial differences in lipid species among women, mostly in the TAG sub-pathway, highlighting the influence of race on the lipidome. Validation in a different study population is needed. Citation Format: ang Li, Ghazaleh Pourali, Kayla R. Getz, Myung Sik Jeon, Jingqin Luo, Chongliang Luo, Adetunji T. Toriola. Untargeted lipidomics reveals racial differences in lipid species among women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2140.