Abstract B100: Germline genetics of chronic inflammation and breast cancer risk in Peru: Building population-specific resources for precision prevention in Latin America
Abstract
Breast cancer is the leading cause of cancer-related mortality among women, particularly in Low and Middle-Income Countries (LMICs), including Peru. Reportedly, the Peruvian population possess substantial Indigenous American ancestry, which remains underrepresented in genomic studies. Chronic inflammation contributes to breast carcinogenesis by promoting immune dysregulation, epithelial–mesenchymal transition, angiogenesis, and metastatic progression. While numerous inflammatory pathways have been implicated in breast cancer biology, the contribution of inherited inflammatory genetic variation to breast cancer susceptibility in Latin American populations remains poorly understood. Thus, we aimed to explore whether germline variants within immune and inflammatory pathways contribute to breast cancer susceptibility in Peruvian women. Patients diagnosed with breast cancer were recruited to be part of The Peruvian Genetics and Genomics of Breast Cancer Study (PEGEN-BC, N=1,811) at the Instituto Nacional de Enfermedades Neoplásicas, a Peruvian reference of cancer treatment that gathers Peruvian patients from all the country. Women without a diagnosis of breast cancer from a pregnancy outcomes study conducted in Lima, Peru, were included as ‘convenience’ controls (N=3,339). Genome-wide genotype data were available for all women, and missing genotypes were imputed using the Michigan Imputation Server (TopMed). Standard quality controls were applied. Breast cancer risk was evaluated using binomial logistic regression adjusted for the first ten principal components of variation. Our targeted analysis evaluated genetic variants distributed across 12 immune and inflammatory pathways-related genes linked to chronic inflammation, namely, IL6, IL6R, IL1B, TNF, TGFB1, IL10, PTGS2 (COX2), CXCL12, CCR5, TLR4, CRP and NFKB. The analysis included variants located within the target genes and in a +/- 250kb window of their 3' and 5' ends. Multiple-testing correction was applied using the Bonferroni method. A total of 20,528 variants across 12 chronic inflammation-related genes were evaluated. Although no genetic variant reached the p value for significance (2.4357E-06), rs4074024 -within the CRP gene- showed a p value of 9.40E-05. Additionally, 19 other variants reached suggestive p values between 2E-04 and 9.40E-04, located across the CRP, CXCL12, PTGS2 and NFKB1 genes. Interestingly, 13 (59.1%) of said variants correspond to the CRP gene, which encodes for the C-reactive protein, a key blood biomarker for chronic, systemic inflammation. Elevated CRP levels strongly correlate to tumor progression, aggressiveness, and a higher risk of recurrence. In conclusion, our results warrant future studies exploring genetic variants at the germline level involving chronic inflammation pathways and breast cancer risk. Further work is needed to confirm associations and address possible heterogeneity by breast cancer subtype within an understudied Peruvian cohort. Solange R. Paredes-Moscosso, Xiaosong Huang, Amanda Corpuz, Bizu Gelaye, Sixto E. Sanchez, Gloria T. Larrabure Torrealva, Michelle A. Williams, Diana L. Juvinao-Quintero, Luis Salinas, Sandro Casavilca-Zambrano, Jeannie Navarro-Vásquez, Ruddy Liendo-Picoaga, Guillermo Valencia, Carlos A. Castañeda, Silvia P. Neciosup, Monica Calderón, Zaida Morante, Patricia Rioja, Jessica Meza, Julio E. Abugattas, Jose M. Cotrina, Victor Castro, Luis Mas, Marco Gálvez-Niño, Katia Roque, Jule Vásquez, Tatiana Vidaurre, Laura Fejerman. Germline genetics of chronic inflammation and breast cancer risk in Peru: Building population-specific resources for precision prevention in Latin America [abstract]. In: Proceedings of the 19th AACR Conference on the Science of Cancer Health Disparities; 2026 Oct 18-21; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2026;35(10 Suppl):Abstract nr B100.