Abstract A060: Breast cancer-associated leukocyte DNA methylation profile in obese African-American women
Authors: Dutta Pranabananda , Wu Yanyuan , Duta Jaydutt V. 
Published: September 2024

Background: DNA methylation (DNAme) is a stable epigenetic mark leading to reduced gene expression. However, genome-wide DNAme profile is susceptible to disease. Therefore, specific genetic DNAme profiles could potentially serve as biomarkers associated with breast cancer (BC) and obesity as its comorbidity. Incidentally, BC-related mortality is higher in African-American women, causing a significant health disparity. In this study, we profiled obesity and breast cancer-related leukocyte DNAme in African-American women to explore methylation- associated biomarkers in these women. Methods: We used 10 African-American women with confirmed breast cancer diagnosis and 10 otherwise healthy African-American women with known Body Mass Index (BMI) &gt; 30 (Obese). DNA was extracted from the buffy coat of peripheral blood using Qiagen DNA extraction kits. We used the next-generation sequencing technology to perform reduced presentation bisulfite sequencing (RRBS) using the Tecan Ovation RRBS kit. We sequenced the libraries on a NextSeq 550 at our Precision Medicine Unit. Single-end 75bp reads were generated and processed using Bismark and mapped against the GRCh38 human genome, and differentially methylated regions (DMR) were derived using MethylKit using a 1 kb window. Gene Ontology and Disease association studies were conducted using DAVID and relapsed-free survival in Kmplot. Additionally, we compared the gene sets with obese and normal DMRs that had previously been obtained similarly. Results: We found that 83% of the DMRs were in the promoter/upstream regions of the nearest genes, and 96% of DMRs were part of CpG islands, indicating potential regulatory functions of these regions. Gene ontology analysis revealed that the DMR-associated genes were also overrepresented in breast carcinoma, Type 2 Diabetes, Obesity, and Tobacco usage, according to the DisGeNET and GAD disease associations databases. Genes with DMRs in their upstream or promoter regions - include PRDM16, PTBP1, RAB1A (lower methylation in cancer with obesity), and Multiple ribosomal genes along with RRAF, XKR4 (higher methylation in cancer with obesity). We observed lower methylation profiles in multiple genes in samples with cancer, which were higher in obese samples without cancer.Conclusion: Our study suggests that a distinct peripheral DNA methylation profile is associated with minority women suffering from both cancer and obesity. Our data show that showed that breast cancer modulates leucocyte DNA methylation profile in obese individuals towards that of a more normal BMI, causing a partial reversal. This potential reversal is primarily in the upstream regions of the genes detected for methylation. The DMR genes in cancer with obesity are significantly associated with overall survival in breast cancer, thus indicating a potential link in understanding the crosstalk between obesity and cancer.

Citation Format: Pranabananda Dutta, Yanyuan Wu, Jaydutt V. Duta. Breast cancer-associated leukocyte DNA methylation profile in obese African-American 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 A060.