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

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.

SUBMITTER: Aleksandrova K

PROVIDER: S-EPMC3388489 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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

Aleksandrova Krasimira K Boeing Heiner H Jenab Mazda M Bueno-de-Mesquita H Bas HB Jansen Eugene E van Duijnhoven Fränzel J B FJ Fedirko Veronika V Rinaldi Sabina S Romieu Isabelle I Riboli Elio E Romaguera Dora D Westphal Sabine S Overvad Kim K Tjønneland Anne A Boutron-Ruault Marie Christine MC Clavel-Chapelon Françoise F Kaaks Rudolf R Lukanova Annekatrin A Trichopoulou Antonia A Lagiou Pagona P Trichopoulos Dimitrios D Agnoli Claudia C Mattiello Amalia A Saieva Calogero C Vineis Paolo P Tumino Rosario R Peeters Petra H PH Argüelles Marcial M Bonet Catalina C Sánchez María-José MJ Dorronsoro Miren M Huerta Jose-María JM Barricarte Aurelio A Palmqvist Richard R Hallmans Göran G Khaw Kay-Tee KT Wareham Nick N Allen Naomi E NE Crowe Francesca L FL Pischon Tobias T

Carcinogenesis 20120319 6

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 p ...[more]

PMID: 22431719

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Project description:BackgroundProspective studies have consistently reported lower colorectal cancer risks associated with higher intakes of total dairy products, total milk and dietary calcium. However, less is known about whether the inverse associations vary for individual dairy products with differing fat contents.Materials and methodsIn the European Prospective Investigation into Cancer and Nutrition (EPIC), we investigated the associations between intakes of total milk and milk subtypes (whole-fat, semi-skimmed and skimmed), yoghurt, cheese, and dietary calcium with colorectal cancer risk amongst 477,122 men and women. Dietary questionnaires were administered at baseline. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusted for relevant confounding variables.ResultsDuring the mean 11 years of follow-up, 4,513 incident cases of colorectal cancer occurred. After multivariable adjustments, total milk consumption was inversely associated with colorectal cancer risk (HR per 200 g/day 0.93, 95% CI: 0.89-0.98). Similar inverse associations were observed for whole-fat (HR per 200 g/day 0.90, 95% CI: 0.82-0.99) and skimmed milk (HR per 200 g/day 0.90, 95% CI: 0.79-1.02) in the multivariable models. Inverse associations were observed for cheese and yoghurt in the categorical models; although in the linear models, these associations were non-significant. Dietary calcium was inversely associated with colorectal cancer risk (HR per 200 mg/day 0.95, 95% CI: 0.91-0.99); this association was limited to dairy sources of calcium only (HR per 200 mg/day 0.95, 95% CI: 0.91-0.99), with no association observed for non-dairy calcium sources (HR per 200 mg/day 1.00, 95% CI: 0.81-1.24).ConclusionsOur results strengthen the evidence for a possible protective role of dairy products on colorectal cancer risk. The inverse associations we observed did not differ by the fat content of the dairy products considered.

Dataset Information

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

Publications

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

Similar Datasets

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