Exploring the Genomic Diversity of Cancer in Latin American Populations

Authors: Alejandro Ruíz-Patiño, Leonardo Rojas, Jairo Zuluaga, Oscar Arrieta, Luis Corrales, Claudio Martín, Sandra Franco, Luis Raez, Christian Rolfo, Natalia Sánchez and Andrés Felipe Cardona.

Published in the Clinical and Translational Oncology on April 6, 2024

Introduction

Precision oncology is changing cancer care by tailoring treatments to the unique genetic and molecular makeup of each person’s tumor. However, most research has focused on people of European ancestry, overlooking the genetic diversity in other parts of the world. Latin American populations, with their mix of European, Native American, African, and Asian ancestries, offer important insights for personalized cancer care. This review explores how genetic ancestry influences cancer epidemiology, tumor biology, and treatment outcomes in Latin American communities, helping to advance precision oncology for these diverse patients.

Overview and Design Methods

• This review article synthesizes the current state of knowledge on the intersection of genetic ancestry and cancer in Latin American populations. The authors conducted a thorough literature search using PubMed, Embase, and Cochrane Library databases, focusing on studies that examined the impact of ancestral proportions on cancer incidence, molecular characteristics, and clinical outcomes within Latin American cohorts. The search was not limited by publication date, allowing for a comprehensive assessment of the evolving landscape in this field.

Key Highlights

• Breast Cancer Insights: Notably, the study identifies an increased incidence of Luminal B and Her2 breast tumors in populations with significant Native American ancestry, marked by specific genetic traits.
• Lung Cancer Patterns: A distinct pattern emerges in EGFR, BRAF and KRAS mutations more prevalent in lung adenocarcinomas among these populations, compared to global averages.
• Colorectal Cancer Findings: Latin American CRC patients have a higher prevalence of germline APC and MLH1 variants
• Prostate Cancer Discoveries: Latin men have higher polygenic risk scores conferring a 3.2-fold increased prostate cancer risk. Additionally, tumors show more TMPRSS2-ERG fusions, TMB-High, and PD-L1 positivity.
• Gastric Cancer: Latin patients exhibit more genomically stable gastric tumors with distinct mutation patterns.
• Liver/Biliary Cancers: Higher rates of Hepatocellular carcinomas harboring unique mutations in AXIN2 and MTOR. Gallbladder cancer incidence is markedly higher in Native American populations.

Key Takeaway Messages

• Genetic Diversity as a Double-edged Sword: The complex genetic admixture of Latin American populations, with ancestral contributions from Europe, Native America, Africa, and Asia, presents both challenges and opportunities. While posing complexities for traditional population genetics methods, this diversity enables the discovery of novel genetic drivers and disease mechanisms underlying cancer in this understudied group.
• Ancestry-Informed Precision Cancer Care: Understanding the unique genetic ancestry profiles and associated tumor molecular signatures of Latin American cancer patients is crucial for developing population-specific risk prediction models, screening approaches, and targeted therapeutic strategies. Integrating ancestry data alongside clinical and molecular biomarkers can enhance the accuracy of prognostic assessments and treatment response forecasting.
• Addressing Disparities through Inclusive Research: The substantial underrepresentation of Latin American individuals in large-scale cancer genomics initiatives has limited a comprehensive understanding of the cancer burden and biology in this diverse population. Expanding collaborative efforts to map the genomic landscape and generate ancestry-specific references systematically is vital for reducing cancer health disparities and ensuring equitable access to precision oncology advances.
• Translating Ancestry-Driven Insights into Clinical Practice: The unique somatic mutation profiles, tumor subtypes, and clinical outcomes observed across different Latin American ancestral backgrounds underscore the need to pivot from a one-size-fits-all approach to more personalized cancer care. Embedding ancestry-informed biomarkers and risk factors into routine clinical decision-making can help optimize early detection, risk stratification, and targeted therapeutic selection for this heterogeneous patient population.

Summary by Amalya Sargsyan, MD

Genomic Ancestry and Cancer Among Latin Americans: A Comprehensive Overview