DOI: 10.1200/go-26-12300 ISSN: 2687-8941

Bridging the Global Genomic Divide: A Transcontinental Analysis of TP53 Mutational Disparities in Breast Cancer

Fernando Augusto Siuta dos Santos, Pedro Dytz Marin, Giulia Scain, Isabela Alicia Fink, Julia Loureiro Chaves Cé, Stéphanie Klein Brum, Mariana Weremeier Weber, Martina de Sá, Rafaela Sumienski Girardi, Solana de Melo
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PURPOSE

Western-centric genomic databases create a critical genomic data gap for low- and middle-income countries (LMICs), risking global therapeutic inequity. This study quantifies transcontinental heterogeneity in breast cancer driver mutations (eg, TP53) across independent global cohorts to expose the biological divergence between Western, African-descendant, and Asian populations.

METHODS

A retrospective in-silico analysis was performed using cBioPortal. The study actively integrated raw genomic data from the TCGA PanCancer Atlas (reference) and the SMC 2018 independent cohort (Asian). TCGA data was clinically stratified by race to isolate Caucasian and Black/African American sub-cohorts. Somatic TP53 alteration frequencies were extracted across 1,270 patients. Disparities were strictly quantified using Chi-square statistics and odds ratios (OR) to estimate the relative risk of aggressive mutational profiles across different ancestral backgrounds.

RESULTS

The integrated multi-cohort dataset comprised 1,270 patients (TCGA: N = 1,084; SMC: N = 186). Genomic analysis demonstrated profound transcontinental divergence in TP53 mutational burden. The independent Asian cohort (SMC) exhibited a 47.85% alteration frequency, significantly higher than the unstratified TCGA baseline (32.66%, P = 8.52 × 10 –6 ). Rigorous demographic stratification further revealed that, compared to the Caucasian sub-cohort (29.29%, n = 751), the risk of harboring a highly aggressive TP53 mutation was significantly elevated in non-Western populations. Specifically, the odds of a TP53 mutation were nearly doubled in both the Black/African American cohort (42.31%, n = 182; OR = 1.77, P = 3.75 × 10 –4 ) and the Asian cohort (OR = 2.21, P < .0001). Despite these population-level biological disparities, current standard-of-care guidelines remain predominantly unadjusted for ancestry-driven genomic risks.

CONCLUSION

This study provides robust quantitative evidence that breast cancer mutational landscapes exhibit severe transcontinental heterogeneity. The significant enrichment of aggressive TP53 mutations in African-descendant and Asian cohorts (exhibiting 1.7-2.2 fold increased odds) proves that universally applying Eurocentric precision medicine paradigms is biologically flawed. Achieving true global cancer equity necessitates aggressively closing the genomic data gap through decentralized, native sequencing initiatives in LMICs.

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