Abstract Background: We previously investigated genetic ancestry associations with breast cancer subtypes in Peruvian women. We found that women with human epidermal growth factor receptor 2 (HER2) over-expressing tumors had higher Indigenous American ancestry than women with other subtypes. We found a suggestive association between African ancestry and triple negative breast cancer (TNBC). We hypothesized that these associations could be due to the presence of germline variants in the Indigenous American genome or the African genome predisposing women to HER2 over-expression or TNBC respectively. We conducted genome wide association analyses to explore this hypothesis. Methods: Blood samples and clinical data were collected from 1195 women with breast cancer at the Instituto Nacional de Enfermedades Neoplasicas in Lima, Peru. Genotypic profiles for 821 women were generated using the Affymetrix Precision Medicine Research Array. Four major breast cancer subtypes were identified using immunohistochemical markers (luminal A, luminal B, triple negative, and HER2 over-expressing). Genetic ancestry was determined using ADMIXTURE. Genome wide association analyses were conducted in PLINK. Results: Three polymorphisms with the lowest p values in the TNBC GWAS are of interest. A variant, rs16910137, at 10q26, is located in an intron of the Glutaredoxin 3 gene (GLRX3 or TXNL2, OR = 2.45, P = 8.60*10-07). The protein encoded by this gene may inhibit apoptosis and play a role in cellular growth. It has also been described as a biomarker for TNBC. Our own RNA-seq data for TXNL2 in 52 Colombian women with breast cancer showed that the expression level of this gene is higher in women with triple negative (N=9) compared to luminal tumors (N=43) (P=0.06). The other two variants, rs12327440 and rs13381183, are located in an intron of the Mitogen-Activated Protein Kinase 4 (MAPK4) gene at 18q21 (OR = 0.44 and 1.94 respectively, P = 4.92*10-07 and 7.230*10-06). RNA-seq data for MAPK4 suggestively showed that the expression level is higher in women with TNBC compared to luminal tumors (P=0.18). The variant in the HER2 over-expressing GWAS with the lowest p value, rs11594103, at 10p11 is located upstream of the Enhancer Of Polycomb Homolog 1 (EPC1) gene (OR = 2.38, P = 8.03*10-07). The encoded protein has been linked to apoptosis and DNA repair among other functions and suggested as involved in the activation of metastasis. Conclusions: Our data suggests that a germline variant within the GLRX3/TXNL2 gene might be associated with the risk of developing TNBC compared to other subtypes. This is particularly interesting in the light that previous work suggested that TXNL2 autoantibodies could be biomarker of TNBC. The MAPK4 and EPC1 genes have been previously implicated in multiple types of cancer and our results indicate that they may play a role in the etiology of specific breast cancer subtypes. This supports the importance of conducting genetic association studies in diverse samples. Citation Format: Katie M. Marker, Tatiana Vidaurre, Jeannie Navarro Vasquez, Valentina Zavala, Silvia Serrano Gomez, Lizeth Tamayo, Renzo Meza Florez, S Casavilca, M Calderon, JE Abugattas, Henry Gómez, Hugo Fuentes, CL Monge Pimentel, Sikai Song, Daniel Cherry, Scott Huntsman, Donglei Hu, Elad Ziv, Laura Fejerman. Breast cancer subtype GWAS in Peruvian breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1589.