title: Serum C-peptide, IGFBP-1 and IGFBP-2 and risk of colon and rectal cancers in the European Prospective Investigation into Cancer and Nutrition.
abstract: Western style diets and lifestyles are associated with increasing rates of obesity, diabetes and insulin resistance. Higher circulating insulin levels may modulate cell proliferation and apoptosis either directly or indirectly by increasing the bioactivity of IGF-I and decreasing the bioactivity of some of its binding proteins. The objective of this study was to determine the association of increasing levels of serum C-peptide, a biomarker of pancreatic insulin secretion, and IGF binding proteins (IGFBP) -1 and -2 with colorectal cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 Western European countries. A total of 1,078 colorectal cancer cases were matched (age, date of blood donation, fasting status, gender, study center) to an equal number of control subjects. Relative cancer risks were estimated using conditional logistic regression models. Serum C-peptide concentration was positively associated with an increased colorectal cancer risk for the highest versus the lowest quintile (OR=1.56, 95% CI=1.16-2.09, p(trend)<0.01), which was slightly attenuated after adjustment for BMI and physical activity (OR=1.37, 95% CI=1.00-1.88, p(trend)=0.10). When stratified by anatomical site, the cancer risk was stronger in the colon (OR=1.67, 95% CI=1.14-2.46, p(trend)<0.01) than in the rectum (OR=1.42, 95% CI=0.90-2.25, p(trend)=0.35). The cancer risk estimates were not heterogeneous by gender or fasting status. No clear colorectal cancer risk associations were observed for IGFBP-1 or -2. This large prospective study confirms that hyperinsulinemia, as determined by C-peptide levels, is associated with an increased colorectal cancer risk.
authors: Nutrition and Hormones Group, IARC-WHO, Lyon, France.
authors: Mazda
authors: M
authors: Jenab
authors: Elio
authors: E
authors: Riboli
authors: Rebecca J
authors: RJ
authors: Cleveland
authors: Teresa
authors: T
authors: Norat
authors: Sabina
authors: S
authors: Rinaldi
authors: Alexandra
authors: A
authors: Nieters
authors: Carine
authors: C
authors: Biessy
authors: Ann
authors: A
authors: Tjønneland
authors: Anja
authors: A
authors: Olsen
authors: Kim
authors: K
authors: Overvad
authors: Henning
authors: H
authors: Grønbaek
authors: Françoise
authors: F
authors: Clavel-Chapelon
authors: Marie-Christine
authors: MC
authors: Boutron-Ruault
authors: Jakob
authors: J
authors: Linseisen
authors: Heiner
authors: H
authors: Boeing
authors: Tobias
authors: T
authors: Pischon
authors: Dimitrios
authors: D
authors: Trichopoulos
authors: Eleni
authors: E
authors: Oikonomou
authors: Antonia
authors: A
authors: Trichopoulou
authors: Salvatore
authors: S
authors: Panico
authors: Paolo
authors: P
authors: Vineis
authors: Franco
authors: F
authors: Berrino
authors: Rosario
authors: R
authors: Tumino
authors: Giovanna
authors: G
authors: Masala
authors: Petra H
authors: PH
authors: Peters
authors: Carla H
authors: CH
authors: van Gils
authors: H Bas
authors: HB
authors: Bueno-de-Mesquita
authors: Marga C
authors: MC
authors: Ocké
authors: Eiliv
authors: E
authors: Lund
authors: Michelle A
authors: MA
authors: Mendez
authors: María José
authors: MJ
authors: Tormo
authors: Aurelio
authors: A
authors: Barricarte
authors: Carmen
authors: C
authors: Martínez-García
authors: Miren
authors: M
authors: Dorronsoro
authors: José Ramón
authors: JR
authors: Quirós
authors: Göran
authors: G
authors: Hallmans
authors: Richard
authors: R
authors: Palmqvist
authors: Göran
authors: G
authors: Berglund
authors: Jonas
authors: J
authors: Manjer
authors: Timothy
authors: T
authors: Key
authors: Naomi E
authors: NE
authors: Allen
authors: Sheila
authors: S
authors: Bingham
authors: Kay-Tee
authors: KT
authors: Khaw
authors: Anne
authors: A
authors: Cust
authors: Rudolf
authors: R
authors: Kaaks
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood*; D016022:Case-Control Studies; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood*; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012004:Rectal Neoplasms / Q000097:blood* / Q000175:diagnosis; D012307:Risk Factors
chemical_list: D002096:C-Peptide; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2