Early-Life Mutagenesis and the Rise of Early-Onset Colorectal Cancer.

Area of Science:

• Oncology
• Microbiology
• Genetics

Background:

• Colorectal cancer (CRC) incidence is increasing globally in individuals under 50.
• Established risk factors do not adequately explain this trend in early-onset CRC.
• The etiology of early-onset CRC remains poorly understood.

Purpose of the Study:

• To propose a novel hypothesis for the rising incidence of early-onset colorectal cancer.
• To investigate the potential role of early-childhood exposure to mutagen-producing bacteria in CRC development.
• To reframe early-onset CRC as a disease initiated by early-life mutagenic exposures.

Main Methods:

• This study advances a hypothesis based on existing literature and biological plausibility.
• The proposed mechanism involves imprinting oncogenic mutations in the developing colorectal epithelium.
• The hypothesis links early-life exposures to tumorigenesis decades later.

Main Results:

• The study hypothesizes that mutagen-producing bacteria in early childhood can lead to oncogenic mutations.
• These mutations, imprinted in the developing gut, may initiate colorectal cancer development.
• This mechanism offers a potential explanation for CRC appearing decades before clinical detection.

Conclusions:

• Early-childhood exposure to mutagenic bacteria is proposed as a significant contributor to lifetime CRC risk.
• This hypothesis provides a framework for understanding the origins of early-onset colorectal cancer.
• Redefining early-onset CRC as a disease rooted in early-life mutagenic exposure may guide future research and prevention strategies.