Background: Adiponectin (APN) is a protein synthesized and secreted by adipocytes into the peripheral blood with pleiotropic functions in lipid/glucose metabolism, and beneficial roles in cardiovascular functions and inflammation. However, circulating APN level is inversely related with body weight. In obesity, decreased APN serum levels correlate with tumor development and progression and are inversely associated with markers of inflammation. In particular APN was shown to reduce TNF-a induced effects on cell proliferation and migration. Study aim's was to explore the correlation of serum APN and TNF-a with CRC risk in relation to obesity.Materials and method: We conducted a case-control study comprising 52 CRC patients 26 women and 26 men, median age 70.5 years (33-86) and 30 healthy subjects, median age 56 years (26-75). Blood samples were obtained from all subjects at the time of diagnosis. The enzyme-linked immunosorbent assay was used to measure APN and TNF-a serum levels. Using the height and weight value of all participants, body mass index (BMI) was calculated as weight in kilograms divided by the square of height in meters.Results: Serum APN in CRC patients were significantly lower than the controls (98.7 ± 55.6 vs 6641 ± 3263 ng/ml), while serum TNF-a were higher than control (168 ± 93 vs 0.5-5.5 pg/ml), p < 0.0001. A significant inverse correlation between the two markers was found, p = 0.006. Calculated BMI (kg/m2) values were <25 (normal weight, n = 23 pts), ≥25 (overweight, n = 17 pts) and ≥29 (obese, n = 12 pts). A inverse correlation was observed between serum APN and BMI, APN levels decreased in relation to BMI increases; while serum TNF-a increases with increasing BMI. Also a negative correlation was present between tumor stage and APN (p < 0.001).Conclusions: APN concentrations are strongly determined by obesity status and its expression is decreased by TNF-a. In our series the negative correlation between tumor stage and circulating APN, suggests that APN may have an important protective role in carcinogenesis induced by inflammation influencing cancer biology regulating cell proliferation and inducing apoptosis. In obesity alteration of APN and TNF-a signaling could be an active local player determining the peritumoral milieu that promotes tumor rise and progression. Our study support that the links between obesity and inflammation and between chronic inflammation and cancer suggest that inflammation might be important in the obesity-cancer link. Background: Adiponectin (APN) is a protein synthesized and secreted by adipocytes into the peripheral blood with pleiotropic functions in lipid/glucose metabolism, and beneficial roles in cardiovascular functions and inflammation. However, circulating APN level is inversely related with body weight. In obesity, decreased APN serum levels correlate with tumor development and progression and are inversely associated with markers of inflammation. In particular APN was shown to reduce TNF-a induced effects on cell proliferation and migration. Study aim's was to explore the correlation of serum APN and TNF-a with CRC risk in relation to obesity. Materials and method: We conducted a case-control study comprising 52 CRC patients 26 women and 26 men, median age 70.5 years (33-86) and 30 healthy subjects, median age 56 years (26-75). Blood samples were obtained from all subjects at the time of diagnosis. The enzyme-linked immunosorbent assay was used to measure APN and TNF-a serum levels. Using the height and weight value of all participants, body mass index (BMI) was calculated as weight in kilograms divided by the square of height in meters. Results: Serum APN in CRC patients were significantly lower than the controls (98.7 ± 55.6 vs 6641 ± 3263 ng/ml), while serum TNF-a were higher than control (168 ± 93 vs 0.5-5.5 pg/ml), p < 0.0001. A significant inverse correlation between the two markers was found, p = 0.006. Calculated BMI (kg/m2) values were <25 (normal weight, n = 23 pts), ≥25 (overweight, n = 17 pts) and ≥29 (obese, n = 12 pts). A inverse correlation was observed between serum APN and BMI, APN levels decreased in relation to BMI increases; while serum TNF-a increases with increasing BMI. Also a negative correlation was present between tumor stage and APN (p < 0.001). Conclusions: APN concentrations are strongly determined by obesity status and its expression is decreased by TNF-a. In our series the negative correlation between tumor stage and circulating APN, suggests that APN may have an important protective role in carcinogenesis induced by inflammation influencing cancer biology regulating cell proliferation and inducing apoptosis. In obesity alteration of APN and TNF-a signaling could be an active local player determining the peritumoral milieu that promotes tumor rise and progression. Our study support that the links between obesity and inflammation and between chronic inflammation and cancer suggest that inflammation might be important in the obesity-cancer link.