Total and high-molecular-weight adiponectin and risk of colorectal cancer: the European Prospective Investigation into Cancer and Nutrition study

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Item Type:	Article
Title:	Total and high-molecular-weight adiponectin and risk of colorectal cancer: the European Prospective Investigation into Cancer and Nutrition study
Creators Name:	Aleksandrova, K., Boeing, H., Jenab, M., Bueno-de-Mesquita, H.B., Jansen, E., van Duijnhoven, F.J., Fedirko, V., Rinaldi, S., Romieu, I., Riboli, E., Romaguera, D., Westphal, S., Overvad, K., Tjonneland, A., Boutron-Ruault, M.C., Clavel-Chapelon, F., Kaaks, R., Lukanova, A., Trichopoulou, A., Lagiou, P., Trichopoulos, D., Agnoli, C., Mattiello, A., Saieva, C., Vineis, P., Tumino, R., Peeters, P.H., Argueelles, M., Bonet, C., Sanchez, M.J., Dorronsoro, M., Huerta, J.M., Barricarte, A., Palmqvist, R., Hallmans, G., Khaw, K.T., Wareham, N., Allen, N.E., Crowe, F.L. and Pischon, T.
Abstract:	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 they were hypothesised 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 pre-diagnostic 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, 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 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.
Keywords:	Total Adiponectin, High-Molecular Weight (HMW) Adiponectin, Non-HMW Adiponectin
Source:	Carcinogenesis
ISSN:	0143-3334
Publisher:	Oxford University Press
Volume:	33
Number:	6
Page Range:	1211-1218
Date:	November 2012
Official Publication:	https://doi.org/10.1093/carcin/bgs133
PubMed:	View item in PubMed

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