Abstract 5516: Identifying DNA methylation biomarkers in Brazilian women of African descent
Authors: Delgado-Cruzata Lissette , de Paula Diego J. Gomes , Gomes Jennifer Vieira , Simão Tatiana A. , Gusmão Leonor , Pinto Luis Felipe Ribeiro , Soares-Lima Sheila C. 
Published: June 2023

Abstract
Breast cancer is the most common cancer, and the leading cause of cancer-related deaths in Brazilian women. Studies have shown that in Brazil while breast cancer mortality has increased in the last decade for all women, mortality in women of African descent has doubled. A recent study showed that Afro-Brazilian women suffer from higher excess breast cancer mortality even after adjusting for extent of disease, year of diagnosis, age and socioeconomic status, which suggests biological factors also contribute to the differences in the clinicopathological make-up of the disease in women in this group. DNA methylation biomarkers, representing a combination of genetic and non-genetic factors, have the potential to be especially valuable when considering the combined contribution of the environment and genetics in breast cancer etiology. Several groups have found differences in DNA methylation levels associated with race and ethnicity in breast cancer. In addition, research has shown that women of different races/ethnicities with similar breast cancer tumor subtypes have distinct DNA methylation patterns. To explore further the association between race, ancestry and DNA methylation, we conducted a study in paired tumor and non-tumor tissue samples of forty-eight Brazilian women who self-identified as Black or Brown and were treated at National Cancer Institute Breast Cancer Hospital in Rio de Janeiro, Brazil. We carried out a DNA methylation profiling analysis using Illumina EPIC (850k) arrays in bisulfite converted DNA originally extracted from frozen tissue samples. A total of 739,883 differentially methylated probes (DMP) were identified, of which a large proportion 6,241 (78.4%) were hypomethylated. Lower DNA methylation was more common on intragenic regions and gene bodies, while hypermethylation was more commonly found on the promoter regions. DNA methylation was often higher in non-tumor than tumor samples. Among our top hits we found genes previously associated with estrogen receptor negative tumor types, CDH4, CERK, PROX1 and ADHFE1, and with high risk of breast cancer mortality (ST6GAL1, LYN, TFF1 and BMP3). A DPM enrichment pathway analysis predicted effects in known signaling pathways and transcriptional misregulation. We are currently analyzing the associations between the top differentially methylated regions with ancestry informative markers, and the clinicopathological characteristics of disease, to gain a better understanding of the role of DNA methylation marks in this population. This study adds to our current knowledge on epigenetics marks that will ultimately help us address mortality due to this disease in this population.
Citation Format: Lissette Delgado-Cruzata, Diego J. Gomes de Paula, Jennifer Vieira Gomes, Tatiana A. Simão, Leonor Gusmão, Luis Felipe Ribeiro Pinto, Sheila C. Soares-Lima. Identifying DNA methylation biomarkers in Brazilian women of African descent. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5516.