Effects of a high soy protein diet on azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colorectal cancer development in mice

Purpose:The incidence of colorectal cancer (CRC) continues to rise, and the dietary protein intake has been suggested as a potential risk factor.Although the carcinogenic potential of animal-derived proteins has been well documented, the role of soy protein in colorectal carcinogenesis is controversial.This study examined the effects of a high soy protein diet on colitis-associated CRC in mice.Methods: Six-week-old BALB/c mice were assigned to 3 groups: 20% soy protein (20S, control), 20% soy protein with carcinogenesis (20SC), and 40% soy protein with carcinogenesis (40SC).Colorectal carcinogenesis was induced with azoxymethane and dextran sulfate sodium, and mice were fed experimental diets for 10 weeks.Disease activity, survival, colon pathology, tumor multiplicity, and inflammatory markers were assessed.Results: The 40SC group tended to have higher disease activity index scores than the 20S and 20SC groups (significant in parametric analysis) and exhibited reduced survival (log-rank p = 0.004).Cox regression analysis showed that the dietary protein level was independently associated with survival (hazard ratio, 0.232, p = 0.010).The colon weight-to-length ratio and mucosal thickness were significantly higher in the 40SC group than in the 20S and 20SC groups, but, the fecal lipocalin-2, ammonia, and plasma tumor necrosis factor- and nitric oxide levels were not significantly different between 40SC and 20SC groups.Although the overall effect of diet on tumor multiplicity was not significant in the negative binomial model, a direct comparison between the 20SC (41.3 4.1) and 40SC (58.7 5.8) groups showed a significant difference in tumor counts.Conclusion: High dietary soy protein intake was associated with aggravated colitis severity and reduced survival in this experimental model, and showed a potential link with increased tumor development under carcinogenic conditions.These results suggest that excessive soy protein intake may modulate inflammation-associated colorectal carcinogenesis, but additional research is needed to determine its significance in human populations.