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

TitleTotal and high-molecular weight adiponectin and risk of colorectal cancer: the European Prospective Investigation into Cancer and Nutrition Study.
Publication TypeJournal Article
Year of Publication2012
AuthorsAleksandrova K, Boeing H, Jenab M, Bueno-de-Mesquita BH, Jansen E, van Duijnhoven FJB, Fedirko V, Rinaldi S, Romieu I, Riboli E, Romaguera D, Westphal S, Overvad K, Tjønneland 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 PH, Argüelles M, Bonet C, Sánchez M-J, Dorronsoro M, Huerta J-M, Barricarte A, Palmqvist R, Hallmans G, Khaw K-T, Wareham N, Allen NE, Crowe FL, Pischon T
JournalCarcinogenesis
Volume33
Issue6
Pagination1211-8
Date Published2012 Jun
ISSN1460-2180
KeywordsAdiponectin, Body Mass Index, Case-Control Studies, Colorectal Neoplasms, Europe, Female, Humans, Male, Middle Aged, Molecular Weight, Obesity, Prospective Studies, Risk Factors
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 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.

DOI10.1093/carcin/bgs133
Alternate JournalCarcinogenesis
PubMed ID22431719