Divergent Colorectal Cancer Risks Following Metabolic Bariatric Surgery: Anatomical Remodeling and the Genotoxic...

Area of Science:

• Gastroenterology
• Oncology
• Bariatric Surgery

Background:

• Metabolic bariatric surgery (MBS) is linked to reduced overall cancer incidence.
• Colorectal cancer (CRC) risk appears to differ based on the type of MBS procedure.
• Roux-en-Y gastric bypass (RYGB) shows a potential increase in long-term CRC risk, unlike sleeve gastrectomy (SG).

Purpose of the Study:

• To develop a biologically plausible mechanistic framework explaining divergent CRC risks after RYGB and SG.
• To investigate the proposed mechanisms driving increased CRC risk following RYGB.

Main Methods:

• Literature review and synthesis of existing data on MBS and CRC risk.
• Development of a mechanistic hypothesis based on surgical anatomy and physiological changes.
• Comparison of proposed mechanisms between RYGB and SG procedures.

Main Results:

• RYGB is hypothesized to increase CRC risk via anatomical bypass and accelerated transit, leading to distal colonic substrate overload.
• This overload may promote a shift in the colonic microbiome toward proteolytic fermentation, creating a genotoxic luminal environment.
• Factors like secondary bile acids, tyramine, hydrogen sulfide, and butyrate depletion are implicated in the RYGB-associated risk.

Conclusions:

• SG may avoid these alterations by preserving gastrointestinal continuity.
• Baseline CRC risk should be considered when selecting MBS procedures.
• Procedure-specific surveillance strategies, particularly after RYGB, are recommended.