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Variaciones geográficas y de edad en los procesos mutacionales en el cáncer colorrectal

Marcos Díaz-Gay^1,2,3,4, Wellington Dos Santos⁵, Sarah Moody⁶

¹Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.

|April 23, 2025

Resumen

Los procesos mutacionales, particularmente de las bacterias productoras de colibactina, varían geográficamente y están relacionados con un aumento de la incidencia de cáncer colorrectal de aparición temprana. Esta exposición puede conducir al desarrollo temprano de tumores y mutaciones de APC.

Área de la Ciencia:

La genómica
Investigación del cáncer
Microbiología

Sus antecedentes:

Las tasas de incidencia del cáncer colorrectal muestran variaciones geográficas y una duplicación reciente en los casos de aparición temprana (menos de 50 años).
Las causas subyacentes del aumento de la incidencia de cáncer colorrectal de aparición temprana siguen siendo en gran medida desconocidas.

Objetivo del estudio:

Investigar la contribución de los procesos mutacionales a las diferencias geográficas y relacionadas con la edad en el cáncer colorrectal.
Identificar firmas mutacionales específicas y sus posibles orígenes ambientales o microbianos.

Principales métodos:

Análisis genómico de 981 casos de cáncer colorrectal de 11 países.
Comparación de la carga de mutación y las firmas en cánceres estables y inestables en microsatélites.
Análisis de asociación de firmas mutacionales específicas con ubicación geográfica, edad de inicio y mutaciones conductoras.

Principales resultados:

Los cánceres colorrectales estables en microsatélites mostraron variaciones significativas en la carga de mutación y las firmas en diferentes países.
Las firmas mutacionales SBS88 e ID18, vinculadas a la colibactina mutagénica bacteriana, fueron más frecuentes en países con mayor incidencia de cáncer colorrectal.
Estas firmas asociadas a la colibactina se enriquecieron significativamente en los cánceres colorrectales de aparición temprana y se relacionaron con las mutaciones conductoras de APC.

Conclusiones:

Existen variaciones geográficas en los procesos mutacionales del cáncer colorrectal, influenciadas por exposiciones mutagénicas.
La exposición temprana a bacterias productoras de colibactina puede ser un factor que contribuye al aumento de la incidencia de cáncer colorrectal de inicio temprano.
Las firmas mutacionales de colibactina juegan un papel en el desarrollo de mutaciones conductoras de APC en el cáncer colorrectal.

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