Total and high-molecular weight adiponectin and risk of colorectal cancer: the European Prospective Investigation into Cancer and Nutrition Study.
Aleksandrova K., Boeing H., Jenab M., Bueno-de-Mesquita HB., Jansen E., van Duijnhoven FJ., Fedirko V., Rinaldi S., Romieu I., Riboli E., Romaguera D., Westphal S., Overvad K., Tjønneland A., Boutron-Ruault MC., Clavel-Chapelon F., Kaaks R., Lukanova A., Trichopoulou A., Lagiou P., Trichopoulos D., Agnoli C., Mattiello A., Saieva C., Vineis P., Tumino R., Peeters PH., Argüelles M., Bonet C., Sánchez MJ., Dorronsoro M., Huerta JM., Barricarte A., Palmqvist R., Hallmans G., Khaw KT., Wareham N., Allen NE., Crowe FL., Pischon T.
Adiponectin-an adipose tissue-derived protein-may provide a molecular link between obesity and colorectal cancer (CRC), but evidence from large prospective studies is limited. In particular, no epidemiological study explored high-molecular weight (HMW) and non-HMW adiponectin fractions in relation to CRC risk, despite them being hypothesized to have differential biological activities, i.e. regulating insulin sensitivity (HMW adiponectin) versus inflammatory response (non-HMW adiponectin). In a prospective, nested case-control study, we investigated whether prediagnostic serum concentrations of total, HMW and non-HMW adiponectin are associated with risk of CRC, independent of obesity and other known CRC risk factors. A total of 1206 incident cases (755 colon and 451 rectal) were matched to 1206 controls using incidence-density sampling. In conditional logistic regression, adjusted for dietary and lifestyle factors, total adiponectin and non-HMW adiponectin concentrations were inversely associated with risk of CRC [relative risk (RR) comparing highest versus lowest quintile = 0.71, 95% confidence interval (CI) = 0.53-0.95, P(trend) = 0.03 for total adiponectin and RR = 0.45, 95% CI = 0.34-0.61, P(trend) < 0.0001 for non-HMW adiponectin]. HMW adiponectin concentrations were not associated with CRC risk (RR = 0.91, 95% CI = 0.68-1.22, P(trend) = 0.55). Non-HMW adiponectin was associated with CRC risk even after adjustment for body mass index and waist circumference (RR = 0.39, 95% CI = 0.26-0.60, P(trend) < 0.0001), whereas the association with total adiponectin was no longer significant (RR = 0.81, 95% CI = 0.60-1.09, P(trend) = 0.23). When stratified by cancer site, non-HMW adiponectin was inversely associated with both colon and rectal cancer. These findings suggest an important role of the relative proportion of non-HMW adiponectin in CRC pathogenesis. Future studies are warranted to confirm these results and to elucidate the underlying mechanisms.