A Pilot Study: Contrasting Genomic Profiles of Lung Adenocarcinoma Between Patients of European and Latin American Ancestry
Por:
Rueda-Zarazua, B, Gutierrez, H, García-Ortiz, H, Orozco, L, Ramírez-Martinez, G, Jiménez-Alvarez, L, Bolaños-Morales, FV, Zuñiga, J, Avila-Moreno, F, Melendez-Zajgla, J
Publicada:
19 may 2025
Resumen:
Lung cancer remains as the leading cause of cancer mortality worldwide. However, while current evidence suggests the existence of genomic differences between populations, indicating different risk factors associated with population-level genetic backgrounds, most studies have concentrated on populations of European ancestry, and more research is needed on non-European populations. We analyzed whole-exome sequencing data from 25 Mexican lung adenocarcinoma patients and compared them with a TCGA-PanCancer cohort enriched with patients of European ancestry as reference. Clinically relevant germline variants in cancer susceptibility genes are more frequent in our cohort (32% vs. 6.4%) than in the reference. Several mutational signatures (SBS32, SBS85, SBS12, SBS19) occurred at significantly higher frequencies in the Mexican cohort compared to the reference (p < 0.0001). Interestingly, the smoking-associated signature SBS4, present in 67.6% of smokers in the reference cohort, was absent in smoking Mexican patients (p < 0.01656). Somatic variant frequencies in SLC36A4 (20%; p < 0.00002), AP1S1 (8%; p < 0.00002), and TP53 (16%; p = 0.00005) showed significant differences from the European reference cohort. We demonstrate that all these observed biases were independent of the sample size. This study uncovers distinct genomic biases in lung cancer carcinogenesis in this population, compared to a European ancestry reference population, suggesting implications for precision medicine strategies in Latin American populations.
Filiaciones:
Rueda-Zarazua, B:
Univ Nacl Autonoma Mexico, Ciencias Biol, Mexico City 04510, Mexico
Inst Nacl Med Genom, Lab Genom Func Canc, Mexico City 14610, Mexico
Gutierrez, H:
Inst Nacl Med Genom, Mexico City 14610, Mexico
García-Ortiz, H:
Inst Nacl Med Genom, Lab Inmunogen & Enfermedades Metab, Mexico City 14610, Mexico
Orozco, L:
Inst Nacl Med Genom, Lab Inmunogen & Enfermedades Metab, Mexico City 14610, Mexico
Ramírez-Martinez, G:
Inst Nacl Enfermedades Resp, Lab Inmunol & Genet, Mexico City 14080, Mexico
Jiménez-Alvarez, L:
Inst Nacl Enfermedades Resp, Lab Inmunol & Genet, Mexico City 14080, Mexico
Bolaños-Morales, FV:
Inst Nacl Enfermedades Resp, Subdirecc Cirugia, Mexico City 14080, Mexico
Zuñiga, J:
Inst Nacl Enfermedades Resp, Lab Inmunol & Genet, Mexico City 14080, Mexico
Escuela Med & Ciencias Salud, Tecnol Monterrey, Mexico City 14380, Mexico
Avila-Moreno, F:
Univ Nacl Autonoma Mexico, Fac Estudios Super Iztacala, Biomed Res Unit UBIMED, Lung Dis & Funct Epigen Lab LUDIFE, Tlalnepantla 54090, Mexico
Inst Nacl Cancerol INCan, Subdirecc Invest Bas, Res Tower, Mexico City 14080, Mexico
Melendez-Zajgla, J:
Inst Nacl Med Genom, Lab Genom Func Canc, Mexico City 14610, Mexico
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