Myosteatosis mediates the link between specific dietary components and colorectal carcinogenesis: from PPLSS multi-center study.

BACKGROUND AND OBJECTIVES: We assumed the specific dietary components may impact colorectal carcinogenesis via ectopic fat accumulation. METHODS AND STUDY DESIGN: The multi-center case-control study analyzed CT-derived body composition parameters and dietary intake in 163 colorectal cancer (CRC) patients and 144 non-CRC controls. Ectopic fat distribution was characterized by elevated low-attenuation muscle area (LAMA) and reduced skeletal muscle density (SMD, myosteatosis). We employed logistic regression to assess diet-body composition-CRC associations, mediation analysis to elucidate ectopic fat's role, and random forest modelling to evaluate variable importance in CRC risk prediction. RESULTS: CRC patients exhibited obvious myosteatosis (68.1 vs. 31.9%, p <0.001), which promoted colorectal carcinogenesis (95%CI: 0.524, 0.935 in men, 95%CI: 0.425, 0.956 in women via reduced SMD). Linear regression revealed diet rich in ani-mal-derived nutrients and carbohydrates increased LAMA (β = 6.31, 95%CI: 0.766, 11.858), but decreased SMD (β = -3.14, 95%CI: -5.173, -1.099) and normal attenuation muscle area (NAMA) in men, while these components elevated visceral adiposity index (VAI) in women (β = 10.8, 95%CI: 1.265, 20.347). Low bean protein consumption decreased NAMA (β = -13.3, 95%CI: -20.812, -5.860) and SMD (β = -2.95, 95%CI: -4.994, -0.908) in men, while increasing VAI (β = 14.6, 95%CI: 0.820, 28.451) in women. Mediation analysis confirmed NAMA (mediated proportion 11.0%, p = 0.026 in men; 7.24%, p = 0.030 in women), LAMA (11.0%, p = 0.040 in men; 14.6%, p = 0.002 in women) and SMD (17.5%, p = 0.004 in men; 15.4%, p = 0.004 in women) mediated the relationship between excessive consumption of animal-derived nutrients and colorectal carcinogenesis. CONCLUSIONS: Myosteatosis, an inconspicuous obesity phenotype, plays key role in colorectal carcinogenesis but can be mitigated by partial substitution of red meat with soy protein.