Genomic ancestry and cancer among Latin Americans

Abstract

Latin American populations, characterized by intricate admixture patterns resulting from the intermingling of ancestries from European, Native American (NA) Asian, and African ancestries which result in a vast and complex genetic landscape, harboring unique combinations of novel variants. This genetic diversity not only poses challenges in traditional population genetics methods but also opens avenues for a deeper understanding of its implications in health. In cancer, the interplay between genetic ancestry, lifestyle factors, and healthcare disparities adds a layer of complexity to the varying incidence and mortality rates observed across different Latin American subpopulations. This complex interdependence has been unveiled through numerous studies, whether conducted on Latin American patients residing on the continent or abroad, revealing discernible differences in germline composition that influence divergent disease phenotypes such as higher incidence of Luminal B and Her2 breast tumors, EGFR and KRAS mutated lung adenocarcinomas in addition to an enrichment in BRCA1/2 pathogenic variants and a higher than expected prevalence of variants in colorectal cancer associated genes such as APC and MLH1. In prostate cancer novel risk variants have also been solely identified in Latin American populations. Due to the complexity of genetic divergence, inputs from each individual ancestry seem to carry independent contributions that interplay in the development of these complex disease phenotypes. By understanding these unique population characteristics, genomic ancestries hold a promising avenue for tailoring prognostic assessments and optimizing responses to oncological interventions.

Keywords: Cancer; Genetic ancestry; Genetic epidemiology; Genome‐wide association study; NA (NA); Polygenic risk score.

Fig. 1

Ancestry-related effects that potentially explain cancer etiology and treatment potentials. Description of diverse ancestries and how different component analyses such as mutational profiling, epigenotype regulation or gene expression define specific subpopulations. Additionally, certain ancestries could relate to divergent QTL expression or immunogenicity. All in all, these differences could alter early diagnoses, the discovery of novel biomarkers for population identification as well as additional population specific therapeutic targets. QTL quantitative trait locus

Fig. 2

Biological characteristics of breast cancer among Hispanics and their association with NA ancestry

Fig. 3

Targetable lung cancer driver genes associated with genetic ancestry among Hispanics (Modified from Carrot-Zhang J, Soca-Chafre G, Patterson N, Thorner AR, Nag A, Watson J, Genovese G, Rodriguez J, et al. Genetic Ancestry Contributes to Somatic Mutations in Lung Cancers from Admixed Latin American Populations. Cancer Discov. 2021 Mar;11(3):591–598)

Fig. 4

Key genomic features of gastric cancer are identified among Hispanics. Comparison of incidence of somatic alterations in select genes involved in RTK/RAS/PI(3)K signaling, cell cycle, cell adhesion, Wnt signaling, and chromatin remodeling, in the TCGA and Hispanics, stratified by CIN (chromosomal instability) and GS (genomically stable) subtypes (Modified from Wang SC, Yeu Y, Hammer STG, Xiao S, Zhu M, Hong C, Clemenceau JR, Yoon LY, Nassour I, Shen J, Agarwal D, Reznik SI, Mansour JC, Yopp AC, Zhu H, Hwang TH, Porembka MR. Hispanic/Latino Patients with Gastric Adenocarcinoma Have Distinct Molecular Profiles Including a High Rate of Germline CDH1 Variants. Cancer Res. 2020 Jun 1;80(11):2114–2124)