Abstract B086: Short-term effects of immigration on the development of breast cancer in women of African descent

Abstract

Abstract Introduction Haitians diagnosed with breast cancer in Haiti experience a significantly worse outcome than immigrants in Miami that appears to be related to 1) more advanced stage, 2) younger age, 3) more ER-negative tumors, and 4) lack of timely effective treatments including restricted access to trastuzumab and radiation. The objective of the study was to evaluate the epigenetic differences by DNA methylation between women of African descent who have breast cancer and are native to Haiti, the USA or who have emigrated from Haiti to the USA. Methods The study was IRB approved and conducted between 2017-2019 at University of Miami (n=50), Ministry of Health Haiti and Innovating Health International (n=35) and Moffit Cancer Center (n=14). DNA were extracted from saliva (DNAGenotek PrepIT-LP), FFPE breast tumor and normal adjacent breast epithelia (QIAmp DNA FFEP kit) when available. Reduced representation bisulfite sequencing was performed by BGI Inc (Cambridge MA) with EZ DNA metylation gold kit (Zymo) and followed by directional BS-sequence library preparation on HISeq x Ten, PE150. Data was processed in methylKit package and analyzed in a two-step filtering process to 1) include 200bp tiled regions to maximize CpG coverage, > 10 read coverage, <400 read coverage, >3 shared CpGs per group or all samples if the number of samples was less than 3 in the group, q <0.05 and 2) study DMRs only in ER+ breast tumors. Results The mean age of Haitian natives (H) (49.4 years), Haitian Immigrants (HI) (51.9 years) and African American (AA) (48.6 years). The H were in the US for a range of 5-47 years. 64.7% of H, 63% of HI and 42.9% of AA were diagnosed at stages III/IV. Differentially methylated regions (DMRs) were assessed between groups for germline, tumor and normal breast epithelial. There were significantly more DMRs in germline DNA than tumor for each comparison group. The DMRs identified in germline DNA; AA vs HI=54,150 DMRs, HI vs H=45,031 and H vs AA=40,461 DMRs. In the tumors, there were more DMRs between HI and AA (556 DMRs) than H vs AA (33 DMRs) and H vs AA (3 DMRs). Pathway analysis of DMRs identified in germline DNA amongst the three groups revealed common tumor molecular mechanisms of cancer, AMPK and CREB signaling. Whereas Wnt3a, EZH2, PI3K and molecules involved in DNA damage and cell cycle were distinct effectors in tumors of each group. Conclusion This work provides data for exploring the biological basis of breast cancer subtypes within the US Black sub-populations stratified by time and nativity. Haitian immigrants and US born Black women with breast cancer have more epigenetic differences and represent unique pathways which drive tumor biology. Citation Format: Vincent DeGennaro, Kaliyah Brown, Danielle A Cerbon, Daniel Karl, Sofia Palacio, Jennifer Garcia, Camille Ragin, Tuya Pal, Susan Vadaparampil, Carmen Gomez, Judith Hurley, Sophia HL George. Short-term effects of immigration on the development of breast cancer in women of African descent [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B086.