Genomic ancestry and cancer among Latin Americans

Clinical & Translational Oncology, Journal Year: 2024, Volume and Issue: 26(8), P. 1856 - 1871

Published: April 6, 2024

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

Language: Английский

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Profiling the Somatic Mutational Landscape of Breast Tumors from Hispanic/Latina Women Reveals Conserved and Unique Characteristics

Cancer Research, Journal Year: 2023, Volume and Issue: 83(15), P. 2600 - 2613

Published: May 5, 2023

Abstract Somatic mutational profiling is increasingly being used to identify potential targets for breast cancer. However, limited tumor-sequencing data from Hispanic/Latinas (H/L) are available guide treatment. To address this gap, we performed whole-exome sequencing (WES) and RNA on 146 tumors WES of matched germline DNA 140 H/L women in California. Tumor intrinsic subtype, somatic mutations, copy-number alterations, expression profiles the were characterized compared with non-Hispanic White (White) The Cancer Genome Atlas (TCGA). Eight genes significantly mutated including PIK3CA, TP53, GATA3, MAP3K1, CDH1, CBFB, PTEN, RUNX1; prevalence mutations these was similar that observed TCGA. Four previously reported Catalogue Mutations (COSMIC) mutation signatures (1, 2, 3, 13) found dataset, along signature 16 has not been other cancer datasets. Recurrent amplifications drivers MYC, FGFR1, CCND1, ERBB2, as well a recurrent amplification 17q11.2 associated high KIAA0100 gene implicated aggressiveness. In conclusion, study identified higher COSMIC affecting women. These results highlight necessity studying underrepresented populations. Significance: Comprehensive characterization genomic transcriptomic alterations Hispanic/Latina patients reveals distinct genetic signatures, demonstrating importance inclusive studies ensure equitable care patients. See related commentary by Schmit et al., p. 2443

Language: Английский

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Pan-cancer analysis reveals homologous recombination deficiency score as a predictive marker for immunotherapy responders

Human Cell, Journal Year: 2021, Volume and Issue: 35(1), P. 199 - 213

Published: Oct. 10, 2021

Language: Английский

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Age, Body Mass Index, Tumor Subtype, and Racial and Ethnic Disparities in Breast Cancer Survival

JAMA Network Open, Journal Year: 2023, Volume and Issue: 6(10), P. e2339584 - e2339584

Published: Oct. 25, 2023

Black women in the United States have higher breast cancer (BC) mortality rates than White women. The combined role of multiple factors, including body mass index (BMI), age, and tumor subtype, remains unclear.To assess association race ethnicity with survival among clinical trial participants early-stage BC (eBC) according to BMI.This cohort study analyzed data, as November 12, 2021, from enrolled between 1997 2010 4 randomized adjuvant chemotherapy trials: Cancer Leukemia Group B (CALGB) 9741, 49907, 40101 well North Central Treatment (NCCTG) N9831, legacy groups Alliance Clinical Trials Oncology. Median follow-up was 9.8 years.Non-Hispanic Hispanic were compared non-Hispanic within subgroups subtype (hormone receptor positive [HR+]/ERBB2 [formerly HER2] negative [ERBB2-], ERBB2+, HR-/ERBB2-), age (<50, 50 <65, ≥65 years), BMI (<18.5, 18.5 <25.0, 25.0 <30.0, ≥30.0).Recurrence-free (RFS) overall (OS).Of 9479 participants, 436 (4.4%) Hispanic, 871 (8.8%) Black, 7889 (79.5%) White. median (range) 52 (19.0-89.7) years. Among HR+/ERBB2- tumors, individuals had worse RFS (hazard ratio [HR], 1.49; 95% CI, 1.04-2.12; 5-year RFS, 88.5% vs 93.2%) individuals, although global test for not significant any subtype. There no OS differences by Race associated young (age <50 years; P = .008); (HR, 1.34; 1.04-1.71; OS, 86.6% 92.0%) 1.62; 1.16-2.29; 86.2% participants. BMIs 25 less 30, having 1.81; 1.23-2.68; 83.2% 87.3%) participants.In this study, racial ethnic disparities identified patients eBC receiving standardized initial care, potentially at-risk subgroups, whom focused interventions may improve outcomes, found.

Language: Английский

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Somatic Landscape of Oncogenic Variants Across the Main Cancer Subtypes in Latin America: A Narrative Review

JCO Global Oncology, Journal Year: 2025, Volume and Issue: 11

Published: Feb. 1, 2025

Variations in somatic genetic alterations can be observed across different cancer types and diverse populations. Understanding the frequency of oncogenic variants specific populations helps elucidate carcinogenesis risk factors, with often serving as treatment markers. Data regarding landscape main tumor subtypes patients from Latin America Caribbean (LAC) have increased recently, highlighting important differences contrasting North America, Europe, Asia. Many these pressing implications screening, factor management, targeted therapies, health care policy. This review aims to synthesize existing information on patients' tumors LAC. We included most frequent LAC: prostate cancer, female breast colon gastric lung cancer. Furthermore, we add that are relevant LAC because their high incidence, subtypes, or aggressive phenotypes, namely gallbladder acral melanoma, hematologic neoplasms, respectively. The data highlight distinct reported prevalences various a spectrum neoplasms. Moreover, it demonstrates an extensive number molecular studies been carried out region, improving level characterization for this complex, admixed population. Nonetheless, many individual countries still scarce altogether missing, underscoring need establish collaborative groups further advance progress comprehensive research area should not substituted other regions seek empower choices improve our outlook.

Language: Английский

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Equitable machine learning counteracts ancestral bias in precision medicine

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 10, 2025

Gold standard genomic datasets severely under-represent non-European populations, leading to inequities and a limited understanding of human disease. Therapeutics outcomes remain hidden because we lack insights that could be gained from analyzing ancestrally diverse data. To address this significant gap, present PhyloFrame, machine learning method for equitable precision medicine. PhyloFrame corrects ancestral bias by integrating functional interaction networks population genomics data with transcriptomic training Application breast, thyroid, uterine cancers shows marked improvements in predictive power across all ancestries, less model overfitting, higher likelihood identifying known cancer-related genes. Validation fourteen demonstrates is better able adjust ancestry populations. The ability provide accurate predictions underrepresented groups, particular, substantially increased. Analysis performance the most continental group, African, illustrates how phylogenetic distance negatively impacts performance, as well PhyloFrame's capacity mitigate these effects. These results demonstrate artificial intelligence (AI) approaches can contribute representation medical research. Ancestral cancer limits effectiveness Here, authors introduce framework adjusts disease signatures based on data, improve medicine ancestries cancers.

Language: Английский

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Germline Genetic Variants in Cancer Predisposition Genes in Patients From Latin America and the Caribbean

JCO Global Oncology, Journal Year: 2025, Volume and Issue: 11

Published: April 1, 2025

The importance of having region-specific data when planning health interventions has become evident in recent years. Nonetheless, several world regions, including Latin America and the Caribbean (LAC), still face significant challenges. These regions need to develop strategies specifically designed consider inherent characteristics their population composite sociodemographic characteristics. More than 20% global cancer incidence arises LAC. Yet, treatment, prevention, follow-up guidelines area are frequently based on studies that mainly include patients from North America, Europe, Asia. As personalized approaches ubiquitous medical practice, amount information emerging LAC risen considerably. In this review, we seek present a comprehensive summary frequency germline genetic variants hereditary syndromes highlight relevant differences associated with patients, founder recurrent variants, while showcasing potential features might be oncology practices.

Language: Английский

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A single nucleotide variant on chromosome 5 residing within NDUFAF2 distinguishes patients with basal-like human breast cancer.

Published: Jan. 22, 2022

Patients diagnosed with basal-like (also known as basal) subtype breast cancer face a more aggressive disease course and dismal prognosis than patients luminal A B molecular subtypes (1-4). We mined published microarray data (5, 6) to understand in an unbiased fashion the most distinguishing genetic transcriptional features of tumors from basal or cancer. identified single nucleotide polymorphism, rs158923, residing within NDUFAF2, among significant differences In separate cohort cancer, we observed transcriptome-wide differential expression NDUFAF2 transcript. Analysis patient survival revealed that primary tumor was correlated distant metastasis-free Sequence variation gene may be important understanding background favor development human

Language: Английский

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A single nucleotide variant on chromosome 5 residing within SCAMP1 distinguishes patients with basal-like human breast cancer.

Published: Jan. 21, 2022

Patients diagnosed with basal-like (also known as basal) subtype breast cancer face a more aggressive disease course and dismal prognosis than patients luminal A B molecular subtypes (1-4). We mined published microarray data (5, 6) to understand in an unbiased fashion the most distinguishing genetic transcriptional features of tumors from basal or cancer. identified single nucleotide polymorphism, rs10942856, residing within SCAMP1, among significant differences In separate cohort cancer, we observed transcriptome-wide differential expression SCAMP1 transcript. Analysis patient survival revealed that primary tumor was correlated distant metastasis-free Sequence variation gene may be important understanding background favor development human

Language: Английский

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A single nucleotide variant on chromosome 5 residing within PLK2 distinguishes patients with basal-like human breast cancer.

Published: Jan. 21, 2022

Patients diagnosed with basal-like (also known as basal) subtype breast cancer face a more aggressive disease course and dismal prognosis than patients luminal A B molecular subtypes (1-4). We mined published microarray data (5, 6) to understand in an unbiased fashion the most distinguishing genetic transcriptional features of tumors from basal or cancer. identified single nucleotide polymorphism, rs15009, residing within PLK2, among significant differences In separate cohort cancer, we observed transcriptome-wide differential expression PLK2 transcript. Analysis patient survival revealed that primary tumor was correlated distant metastasis-free Sequence variation gene may be important understanding background favor development human

Language: Английский

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