Abstract PR05: Ancestry as a potential modifier of gene expression in luminal B tumors among Colombian women
Authors: Serrano-Gomez Silvia J. , Sanabria Carolina , Baddoo Melody C. , Cruz-Rodriguez Nataly , Garai Jone , Hernandez-Suarez Gustavo , Mejia Juan Carlos , Miele Lucio , Hicks Chindo , Fejerman Laura , Zabaleta Jovanny 
Published: March 2017

Background: Differences in outcome of breast cancer according to race/ethnicity have been reported. African American women have higher breast cancer-specific mortality rates compared to non-Hispanic White women (NHW). Although these differences have been attributed to the high prevalence of basal-like subtype among African Americans, these women have also less favorable outcome in less aggressive tumors when compared to NHW. Hispanic/Latino (H/L) populations are a genetically admixed and heterogeneous group, with variable levels of European, Native American and African ancestries. Some studies suggest that breast cancer-specific mortality is higher in U.S. Latinas compared to NHW even after adjustment for socioeconomic status and education. The molecular profile of breast cancer has been widely described in NHWs but knowledge is lacking in Latinas. We have previously reported that the most prevalent breast cancer intrinsic subtype in Colombian women was Luminal B. In this study we explored ancestry-associated differences in molecular profiles of luminal B tumors among these highly admixed women.

Methods: To identify ancestry-associated differentially expressed genes in Luminal B tumors, we performed a whole-transcriptome RNA-seq analysis in 42 luminal tumors (21 Luminal A and 21 Luminal B) from Colombian women. Genetic ancestry was estimated from a panel of 80 ancestry-informative markers (AIM). We categorized patients according to luminal subtype and to the proportion of European ancestry (Low European ancestry group: ancestry proportion below the median; High European ancestry: ancestry proportion above the median).. We compared luminal B against luminal A tumors according to the assigned ancestry groups. We used DESeq2 package form R to test differential gene expression between the two tumor subtypes and by ancestry category. Genes with adjusted pvalue less than 0.05 were considered statistical significant.

Results: We found 30 differentially expressed genes (pvalue &lt; 0.05) by genetic ancestry among Luminal B tumors from which 27 were differentially expressed in the less European luminal B tumors and 3 in the more European group. Tests of interaction suggest that ancestry is a statistically significant modifier of expression for the following genes for Low European Ancestry group: CENPF, SNORA54, AIF1L, TNFSF13, LRRC1, ARHGAP33, ONECUT2, CDK12, BUB1, NTRK2, HES1); and FDXACB1, RAB26, ATP8B3 for the High European Ancestry group. An exploratory analysis of these genes reveals enrichment of pathways associated to ERBB signaling in the Low European Ancestry group.

Conclusions: Our results suggest that the proportion of European genetic ancestry in Colombian women might modify gene expression in luminal B tumors. Further analysis will be needed to confirm these findings.

Citation Format: Silvia J. Serrano-Gomez, Carolina Sanabria, Melody C. Baddoo, Nataly Cruz-Rodriguez, Jone Garai, Gustavo Hernandez-Suarez, Juan Carlos Mejia, Lucio Miele, Chindo Hicks, Laura Fejerman, Jovanny Zabaleta. Ancestry as a potential modifier of gene expression in luminal B tumors among Colombian women. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr PR05.