Abstract PO-203: Assessment of previously reported polygenic risk score for breast cancer in Peruvian women
Authors: Zavala Valentina A. , Vidaurre Tatiana , Huang Xiaosong , Casavilca Sandro , Navarro Jeannie , Williams Michelle A. , Sanchez Sixto E. , Gelaye Bizu , Fejerman Laura 
Published: January 2022

Background: Breast cancer is the most common cancer among women worldwide. Mutations in high and moderate penetrance genes account for ~10% of breast cancer cases. The remaining genetic predisposition is explained by multiple common genetic variants of relatively small effect. Genome-wide association studies in individuals of mostly European and Asian genetic ancestry have identified multiple risk-associated loci which can be combined into a polygenic risk score (PRS) to predict breast cancer. Our aim was to assess the association of a 313 polymorphism-PRS score (313-PRS) previously published and breast cancer risk in women of a relatively high proportion of Indigenous American ancestry from Peru. Methods: Breast cancer patients were recruited at the Instituto Nacional de Enfermedades Neoplásicas in Lima, Peru, to be part of The Peruvian Genetics and Genomics of Breast Cancer Study (PEGEN-BC, N=1,755). Women without a diagnosis of breast cancer from a pregnancy outcomes study conducted in Lima, Peru, were included as ‘convenience' controls (N=3,342). Genome-wide genotype data were available for all women and missing genotypes were imputed using the Michigan Imputation Server including individuals from 1000 Genomes Project phase III as the reference panel. The 313 polymorphisms were extracted from the imputed data set for further analysis without imputation-r2 filter. Logistic regression was used to test the association between standardized PRS residuals (after adjustment for genetic ancestry) and breast cancer risk. Results: The 313-PRS was positively associated with breast cancer risk in women from Lima, Peru. (OR lowest decile vs. intermediate deciles=0.56, 95%CI= 0.44-0.71, p= 0.00001; OR highest decile vs. intermediate deciles=1.58, 95%CI=1.27-1.95, p= 0.000035). Analysis stratified by quartiles of Indigenous American ancestry did not show heterogeneity. AUROC curve analysis showed similar estimates for all quartiles of Indigenous American ancestry ranging from 0.59 (Q1-lowest ancestry) to 0.61 (Q4-highest ancestry). Conclusion: We confirmed the association between the previously published 313-PRS and breast cancer risk in highly Indigenous American women from Peru. The magnitude of the association and AUROC curve were not statistically significantly different by quartiles of Indigenous American ancestry. The similarity in the AUROC curve estimates by ancestry in a study where the highest ancestry quartile (Q4) includes women with more than 91% Indigenous American ancestry suggests that PRS developed in mostly European women could be used in Latin American populations of high Indigenous American ancestry.

Citation Format: Valentina A. Zavala, Tatiana Vidaurre, Xiaosong Huang, Sandro Casavilca, Jeannie Navarro, Michelle A. Williams, Sixto E. Sanchez, Bizu Gelaye, Laura Fejerman. Assessment of previously reported polygenic risk score for breast cancer in Peruvian women [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-203.