title: 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.
authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany. krasimira.aleksandrova@dife.de
authors.forename: Krasimira
authors.initials: K
authors.lastname: Aleksandrova
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: Mazda
authors.initials: M
authors.lastname: Jenab
authors.forename: H Bas
authors.initials: HB
authors.lastname: Bueno-de-Mesquita
authors.forename: Eugene
authors.initials: E
authors.lastname: Jansen
authors.forename: Fränzel J B
authors.initials: FJ
authors.lastname: van Duijnhoven
authors.forename: Veronika
authors.initials: V
authors.lastname: Fedirko
authors.forename: Sabina
authors.initials: S
authors.lastname: Rinaldi
authors.forename: Isabelle
authors.initials: I
authors.lastname: Romieu
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.forename: Dora
authors.initials: D
authors.lastname: Romaguera
authors.forename: Sabine
authors.initials: S
authors.lastname: Westphal
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.forename: Marie Christine
authors.initials: MC
authors.lastname: Boutron-Ruault
authors.forename: Françoise
authors.initials: F
authors.lastname: Clavel-Chapelon
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.forename: Annekatrin
authors.initials: A
authors.lastname: Lukanova
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.forename: Pagona
authors.initials: P
authors.lastname: Lagiou
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Trichopoulos
authors.forename: Claudia
authors.initials: C
authors.lastname: Agnoli
authors.forename: Amalia
authors.initials: A
authors.lastname: Mattiello
authors.forename: Calogero
authors.initials: C
authors.lastname: Saieva
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.forename: Petra H
authors.initials: PH
authors.lastname: Peeters
authors.forename: Marcial
authors.initials: M
authors.lastname: Argüelles
authors.forename: Catalina
authors.initials: C
authors.lastname: Bonet
authors.forename: María-José
authors.initials: MJ
authors.lastname: Sánchez
authors.forename: Miren
authors.initials: M
authors.lastname: Dorronsoro
authors.forename: Jose-María
authors.initials: JM
authors.lastname: Huerta
authors.forename: Aurelio
authors.initials: A
authors.lastname: Barricarte
authors.forename: Richard
authors.initials: R
authors.lastname: Palmqvist
authors.forename: Göran
authors.initials: G
authors.lastname: Hallmans
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: Nick
authors.initials: N
authors.lastname: Wareham
authors.forename: Naomi E
authors.initials: NE
authors.lastname: Allen
authors.forename: Francesca L
authors.initials: FL
authors.lastname: Crowe
authors.forename: Tobias
authors.initials: T
authors.lastname: Pischon
mesh_terms: D052242:Adiponectin / Q000097:blood*; D015992:Body Mass Index; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood* / Q000473:pathology; D005060:Europe; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D009765:Obesity / Q000097:blood* / Q000150:complications / Q000473:pathology; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin